Session 277 Cataractogenesis

Transcription

ARVO 2016 Annual Meeting Abstracts
277 Cataractogenesis
Monday, May 02, 2016 3:45 PM–5:30 PM
Exhibit/Poster Hall Poster Session
Program #/Board # Range: 2497–2520/B0113–B0136
Organizing Section: Lens
Program Number: 2497 Poster Board Number: B0113
Presentation Time: 3:45 PM–5:30 PM
lanosterol reverse protein aggregation in cataracts
Jie Zhu1, Ling Zhao1, 2, Xiangjun Chen3, Sha Wang1, 3, Huimin Cai4, 5,
Rui Hou5, Wenqiu Wang1, Tingshuai Jiang1, Yong-Bin Yan3,
Kang Zhang1, 4. 1University of California San Diego, Shiley
Eye Institute and Biomaterials and Tissue Engineering Center,
Institute for Engineering in Medicine, La Jolla, CA; 2Zhongshan
Ophthalmic Center, Sun Yat-sen University, State Key Laboratory
of Ophthalmology, Guangzhou, China; 3Tsinghua University, State
Key Laboratory of Membrane Biology, School of Life Sciences,
Beijing, China; 4Molecular Medicine Research Center, West China
Hospital, Sichuan University, Chengdu, China; 5Guangzhou KangRui
Biological Pharmaceutical Technology Company Ltd., Guangzhou,
China.
Purpose: Cataracts are the most common cause of blindness
worldwide, and currently the only treatment is surgical removal of
cataractous lenses. The precise mechanisms by which lens proteins
maintain lens transparency are largely unknown. Lanosterol is
an amphipathic molecule enriched in the lens. It is synthesized
by lanosterol synthase (LSS) in a key cyclization reaction of a
cholesterol synthesis pathway. We investigated a role of LSS
mutations in congenital cataracts in humans and in animal models.
Methods: Exome capture were performed to screen for mutations
in the LSS gene in congenital cataracts. LSS mutant knockout mice
were generated by CRISPR-Cas technology and their phenotypes
characterized.
Results: We identified two distinct homozygous LSS missense
mutations (W581R and G588S) in two families with congenital
cataracts. Engineered expression of wild-type (WT), but not
mutant LSS, prevents intracellular protein aggregation of various
cataract-causing mutant crystallins. Treatment by lanosterol, but not
cholesterol, significantly decreased pre-formed protein aggregates
both in vitro and in cell transfection experiments. We further
showed that lanosterol treatment could reduce cataract and increase
transparency in dissected rabbit cataract lenses in vitro and cataract
in vivo in dogs. The critical role of lanosterol in cataract formation
is supported by the observation that LSS missense mutation mouse
recapitulates the human cataract disease phenotype.
Conclusions: Our study identifies lanosterol as a key molecule in the
prevention of lens protein aggregation and points to a novel strategy
for cataract prevention and treatment.
Commercial Relationships: Jie Zhu, None; Ling zhao, None;
Xiangjun Chen; Sha Wang, None; Huimin Cai, None; Rui Hou,
None; Wenqiu Wang, None; Tingshuai Jiang, None; YongBin Yan, None; Kang Zhang, None
Support: 973 Project (2015CB94600, 2012CB917304), 863 Program
(2014AA021604), NSFC (31327901), State Key Laboratory of
Ophthalmology, and State Key Laboratory of Membrane Biology
A method for the selection of cataract disintegrating compounds
and their use for reversal of crystalline lens opacification
Shiri Zayit-Soudry1, Michael Mimouni1,
Marina Chemerovski-Glikman2, Yarden Dagan2, Esraa Haj2,
Lihi Adler-Abramovich2, Daniel Segal2, Ehud Gazit2.
1
Ophthalmology, Rambam Health Care Campus, Technion- Israel
Institute of Technology, Haifa, Israel; 2Molecular Microbiology and
Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv
University, Tel Aviv, Israel.
Purpose: To describe a novel ex vivo assay for examining the
efficacy of various compounds for the reversal of human crystalline
lens opacification in the search for pharmacological treatment for
cataract.
Methods: After obtaining informed consent, fragments of cataractous
lenses were collected from patients undergoing routine clear
corneal incision phacoemulsification cataract surgery. Following
quantification of total protein concentration in each cataract sample
using the standard Bradford assay, the concentration was adjusted to
obtain an optimal absorbance value. Ex vivo cataract samples were
then incubated with several concentrations of various compounds
being screened for cataract disintegration effect. Reversal of protein
aggregates was monitored several times a day up to 48 h using the
common turbidity assay. In between measurements samples were
kept at 37 °C with constant shaking.
Results: Each compound selected for screening was tested on
cataract samples obtained from 5-10 different patients, in triplicates.
Initial total protein concentrations ranged between 1-10 mg/mL and
after adjustment for optimal absorbance final concentrations ranged
between 0.5-3 mg/mL. Of the 15 compounds screened, five showed
no effect on protein turbidity measurement over time, while five
other showed inconsistent results. Treatment with five compounds
resulted in significant reduction in the optical density of the solution,
reflecting restoration of transparency of the cataractous samples, two
of which showed a dose-dependent effect. Among them each agent
demonstrated different efficacy and unique kinetics.
Conclusions: This simple yet innovative experimental approach
implements spectrophotometric principles to enable direct testing
of the impact of potential compounds on disintegration of actual
human crystalline lens material ex vivo. Further biophysical studies,
currently conducted by our group, will provide mechanistic insight on
the cataract reversal effect.
Commercial Relationships: Shiri Zayit-Soudry, None;
Michael Mimouni, None; Marina Chemerovski-Glikman, None;
Yarden Dagan, None; Esraa Haj, None; Lihi Adler-Abramovich,
None; Daniel Segal, None; Ehud Gazit, None
Coffee (Caffeine) inhibits Cataract Formation in Humans
Shambhu D. Varma, Krish Chandrasekaran. Ophthalmology, Univ of
Maryland Sch of Med, Baltimore, MD.
Purpose: We have previously shown that caffeine prevents
cataractogenesis induced by high sugar levels as well as by UV.
It does so by scavenging reactive oxygen species as well as by
providing a metabolic support. The purpose of the present study was
to examine the possibility of a correlation between caffeine intake
and the prevalence of human cataract.
Methods: Prevalence of blindness due to various eye diseases
published by WHO was used to obtain information on contribution
of cataracts. Data on cataract blindness was then grouped in five
zones according to its prevalence. Per capita coffee consumption
These abstracts are licensed under a Creative Commons Attribution-NonCommercial-No Derivatives 4.0 International License. Go to http://iovs.arvojournals.org/
to access the versions of record.
was obtained from the FAO http://www.griequity.com/resources/
BusinessGuides/DemographicsData/energy/energy-resource) and
other agricultural sources. Caffeine derived from the coffee consumed
was calculated from its percentage composition (~1%).
Results: The percentages of cataract blindness (Mean ±SD, N>6)
were 55.25 ± 6.56, 51.68,± 6.51, 44.21±8.74, 26.28±4.39 and
5.21±0.75 in zones representing the African, American, Eastern
Mediterranean, and Western and Eastern European regions. Caffeine
consumption in the respective zones ranged from 0, 5.6±2.72,
34.28±21.94, 48.02±46.28, 213.83±61.58 (Mg/day). Thus there was
an inverse correlation between the incidence of cataract blindness and
caffeine intake, thus showing its statistically significant preventive
effect; apparent also by regression analysis of the entire data (figure
below).
Conclusions: The inverse correlation between the prevalence of
cataract blindness and caffeine intake dependent on coffee drinking
strongly suggests that this substance inhibits human cataract
formation, in addition to its many other beneficial effects exerted
against several neurological and cardiovascular complications,
longevity and delaying the onset of diabetes. The results are in
conformity with our previous studies showing its effectiveness in
inhibiting cataract formation in the animal models.
Inverse correlation between cataract blindness (%) and caffeine
intake. Spearman’s rank order correlation coefficient. -0.89; P<
0.001; R2 = ~0. 8
Commercial Relationships: Shambhu D. Varma, None;
Krish Chandrasekaran
Age-related cataract and expression level of decorin in human
eye: association with opacity severity
Shinsuke Shibata, Naoko Shibata, Teppei Shibata, Naoki Tanimura,
Hiroshi Sasaki, Eri Kubo. Department of Ophthalmology, Kanazawa
Medical University, Kanazwa, Japan.
Purpose: In an earlier study, we showed that DCN (decorin
proteoglycan) expression level was increased among lens epithelial
cells (LECs) using a posterior capsule opacity (PCO) rat model, albeit
the reason was unclear. In the present study, we examined expression
levels of DCN in human cataractous aqueous humor and LECs.
Methods: Approval was granted by Institutional Review Board,
Kanazawa Medical University. Subjects included 82 cataractous
eyes examined at Kanazawa Medical University Hospital, Ishikawa,
Japan, from April to September, 2015. Age at time of presentation,
subtype and severity of opacity according to WHO cataract
classification system were recorded. Concentrations of DCN protein
in aqueous humor were determined using Human DCN ELISA. DCN
mRNA expression level in LECs was determined using real-time RT
PCR.
Results: DCN was found in aqueous humor, but the concentration
varied among subjects showing no association with age, cataract
subtype or grade. Expression of DCN mRNA in LECs differed
markedly among subjects; however, it was significantly increased in
eyes with posterior capsular (PSC) cataract grade 2-3.
Conclusions: To the extent of the authors’ knowledge, this is the
first report describing DCN secreted in human aqueous humor and
increased levels of DCN in LECs of human patients with advanced
posterior capsular cataract. DCN may be involved in progression of
PSC cataract.
Commercial Relationships: Shinsuke Shibata, None;
Naoko Shibata, None; Teppei Shibata, None; Naoki Tanimura;
Hiroshi Sasaki, None; Eri Kubo, None
MicroRNA-34a promotes mitochondria dysfunction induced
apoptosis in human lens epithelial cell by targeting Notch2
Fan Fan1, Yi Luo1, Jianhui Zhuang2, Xin Liu1. 1Ophthalmology, EYE
& ENT Hospital of Fudan University, Shanghai, China; 2Cardiology,
Shanghai Tenth People’s Hospital of Tongji University, Shanghai,
China.
Purpose: Human lens epithelial cells (HLECs) apoptosis is a
common pathogenic mechanism in age-related cataract (ARC). The
role of miRNAs in the eye is beginning to be explored following
recent detection by miRNA expression analyses. In this study, we
explored the role of miR-34a in regulating the apoptosis in HLECs.
Methods: Quantitative real-time PCR (qRT-PCR) was used to
determine the expression level of miR-34a and pyrosequencing was
performed to dissect the DNA methylation percentages of miR-34a
promoter in both cataractous and transparent lenses. MicroRNA
mimics and small interfering RNA were transfected into HLECs.
In vitro apoptosis, mitochondria function and oxidative stress were
assessed in transfected HLECs. The expression of targeted gene was
determined by qRT-PCR and western blotting, and confirmed with
dual luciferase reporter assay. The potential roles of identified target
gene in apoptosis were also evaluated.
Results: The expression of miR-34a was increased in lens epithelial
samples of ARC compared to the transparent group, whereas
no significant difference in methylation percentages of miR34a promoter was detected between the two groups. In cultured
HLECs, miR-34a increased reactive oxygen species production and
induced apoptosis as determined by flow cytometry and stimulation
of caspase-3,7 activity. Overexpression of miR-34a promoted
mitochondria-involved apoptosis through activation of caspase 9,
disruption of mitochondria membrane potential and enhancement
of cytochrome C release. Furthermore, miR-34a inhibited Notch1/
Notch2 expression and targeted 3’ un-translational region of Notch1/
Notch2 mRNA. Otherwise, knockdown of Notch2 but not Notch1
could trigger mitochondria-involved apoptosis.
Conclusions: MicroRNA-34a is increased in cataratous lens and may
be involved in mitochondria-mediated apoptosis and oxidative stress
by targeting Notch2.
Aβ in aqueous humor showed the similar changes as in the anterior
capsule in ARC patients (Figure 1). In contrast, the expression
of APP increased from Group A to C and decreased in Group D
(Figure 2). The enzymatic activity of β-secretase was decreased in
ARC specimens. The enzymatic activity of β- secretase was also
found decreased in the cultured HLECs treated with H2O2, along
with decreased Aβ and increased APP expression. In addition, we
identified that low concentration of Aβ could relieve H2O2 induced
cell damage in HLECs.
Conclusions: The expression of Aβ was decreased in the early
and medium term of the onset of ARC, induced by the decrease of
β- secretase, and increased in the terminal stage of cataract, which
might be due to the feedback of increased APP expression. Low
concentration of Aβ might play a protective role in cataractogenesis.
Commercial Relationships: Fan Fan, None; Yi Luo, None;
Jianhui Zhuang, None; Xin Liu, None
Support: National Natural Science Foundation of China (81371002),
and the Cutting-Edge Technology Combined PR Project of Shanghai
Shen Kang Hospital Development Centre (SHDC12012104)
Changes of β-amyloid in age-related cataract and its protection
on lens epithelial cells
Tianyu Zheng, Jie Xu, Yi Lu. EYE and ENT Hosp of Fudan Univ,
Shanghai, China.
Purpose: Some studies demonstrated that cataract shared common
characteristics with the conformational diseases, which are defined as
a disease due to abnormal aggregation of protein, such as Alzheimer
disease (AD). β-amyloid (Aβ) might be the key pathogenetic factor
of AD. Some studies demonstrated that Aβ might also be related with
age-related cataract (ARC). Our study is to evaluate the changes of
Aβ expression in ARC patients and its effect on cultured human lens
epithelium cells (HLECs).
Methods: We obtained lens anterior capsule and aqueous humor
from ARC patients during cataract surgery. The specimens with
ARC were divided into four groups according to the lens opacities
classification system III (LOCS III) : Group A: C2-3N1-2; Group B:
C4-5N1-2; Group C: C2-3N3-4; Group D: C4-5N4-5. We used WB,
immunofluorescence, ELISA and RT-PCR to detect the expression
of Aβ and β-amyloid precursor protein (APP). We also employed
β-secretase activity assay. Besides, we applied cell viability assay to
evaluate the effect of Aβ on the viability of HLECs under oxidative
conditions.
Results: The expression of Aβ in ARC lens anterior capsule
decreased from Group A to C, compared with the normal specimens,
and finally increased in Group D (Figure 1). The concentration of
FIGURE 1. WB analysis, IF and ELISA of Aβ in lens capsules and
aqueous humor.Group A- D: samples from the early to the final stage
of ARC.
FIGURE 2. WB analysis, RT-PCR and IF of APP in lens capsules.
Commercial Relationships: Tianyu Zheng; Jie Xu, None; Yi Lu,
None
Support: he National Natural Science Foundation of China (NSFC)
No. 81300747, and the Specialized Research Fund for the Doctoral
Program of Higher Education (SRFDP) No. 20130071120096.
Membrane association of alpha-crystallins with cataract
formation in the ICR/f rat
Stephen Barnes1, Supraja R Sridhar2, Mason W Harris1,
Landon Wilson1, Kelly Walters2, Ali Arabshahi1, Janusz Kabarowski3.
1
Pharmacology & Toxicology, University of Alabama at Birmingham,
Birmingham, AL; 2Chemistry, University of Alabama at Birmingham,
Birmingham, AL; 3Microbiology, University of Alabama at
Birmingham, Birmingham, AL.
Purpose: The Ihara hereditary cataractous rat (ICR/) develops
bilateral lens cataracts spontaneously in 10-12 weeks. It is considered
an important model of senile cataract disease. We have shown in
this model using imaging mass spectrometry that αA-crystallin
undergoes an accelerated rate of proteolysis into at least 16 peptide
species compared to non-cataractous rats. In the present study we
have examined whether αA-crystallin and other lens protein undergo
changes in cellular compartmentation and whether this is associated
with corresponding changes in lens lipid distribution.
Methods: Using the ICR/f rat colony at UAB, groups of rat were
sacrificed at different ages during the stages of appearance of lens
cataracts (30, 45, 60, 80, and 100 days of age) as well as at later ages
(120, 140 and 180 days of age). Lens were recovered and quickly
frozen in liquid N2. Lens were ground to a powder in liquid N2
using a glass pestle and mortar and proteins extracted with 50 mM
Tris-HCl, pH 7.4 containing Roche protease inhibitor cocktail for
water-soluble fraction, 6 M urea-50 mM Tris-HCl, pH 7.4, to recover
membrane-associated fraction and 1% SDS-glycine buffer, pH 8.8
for a lipid-soluble fraction. Each fraction was analyzed by 15%-SDSPAGE and proteins visualized using Coomassie Blue. Lens lipids
extracted with chloroform-methanol were subject to MSMS(ALL)
and differential ion mobility mass spectrometry.
Results: At day 30, >80% of the lens proteins were in the watersoluble fraction. The lens was optically clear. At each time point
after this, the amount of water-soluble protein declined. Initially,
there was an increase in the water-insoluble, urea-soluble fraction,
but as the rats got older, the proportion in the urea-insoluble, SDSsoluble fraction had an even greater increase, so much so that at
180 days >80% of the proteins were in this fraction. Imaging mass
spectrometry of rodent lens lipds revealed that the outer cortical
region of the lens was enriched with diacyl lipids (predominantly
phosphatidylcholines and sphingomyelins). However, with aging
there was a large decrease in the diacyl species in the nuclear region
which were replaced by the corresponding monacyl species.
Conclusions: Aging in the ICR/f rat is accompanied by first
increasing extrinsic membrane association and then intrinsic
membrane association. This is accompanied by altered membrane
composition, a potential driving force of cataract formation.
Commercial Relationships: Stephen Barnes, None; Supraja
R Sridhar, None; Mason W Harris, None; Landon Wilson;
Kelly Walters, None; Ali Arabshahi, None; Janusz Kabarowski,
None
Support: NEI EY020963
Microphthalmus: Congenital Cataract Surgery and SOX2 Gene
Evaluation
Davide Borroni2, Araniko Pandey1, Eriks Elksnis2, Zita Krumina3,
Ineta Orube2, Elize A. Sture2. 1Department of Ophthalmology,
Lumbini Eye Institute, Lumbini, Nepal; 2Department of
Ophthalmology, Riga Stradins University, Riga, Latvia; 3Department
of Genetics, Riga Stradins University, Riga, Latvia.
Purpose: Congenital cataracts rappresent 25% to 30% of avoidable
blindness and microphthalmus has been found in 7% to 17% of these
patients. Our purpose is to report the outcomes and complications of
congenital cataract sugery with Intraocular-Lens(IOL) implantation
in Microphthalmic eyes. The aims of the surgery are to decrease
amblyopia, strabisums and give a full visual development to visual
system. SOX2 gene has been identified as a major causative gene of
microphthalmus. Screening of SOX2 was performed.
Methods: The study involved 20 microphthalmic eyes from 14
children younger than 3 years of age with congenital cataract.
Surgeries consisted in aspiration of the lens and IOL implantation.
Eyes with inflammation, ocular trauma, aniridia, chorioretinal
coloboma or vitreo-retinal diseases were excluded. 6 patients had
bilateral cataract. The outcome measures were Intraocular Pressure
(IOP), Best-Corrected Visual Acuity (BCVA) intraoperative and
postoperative complications. Genomic DNA was extracted from
blood. SOX2 coding region was amplified and PCR product were
sequenced with Big Dye Terminator v3.1 (Applied Biosystems,
Foster City, CA). Initially identified changes were confirmed by
additional independent PCR and sequencing experiments.
Results: Mean age at the time of surgery was 23.9 ± 1.7 months.
Mean ocular axial length was 18.6 ± 0.7 mm. Mean preoperative IOP
was 9.3 ± 1.2 mmHg and 10.8 ± 2.7 mmHg on final followup and no
intraoperative complications happened. Postoperative complication
hapened in one eye (the shortest one with 17.9mm of axial lenght)
who developed secondary visual axis opacification. Preoperative
and postoperative BCVA was 2.01 ± 0.89 logMAR and 0.31 ± 0.06
logMAR in bilateral cases and 1.81 ± 0.97 logMAR and 0.32 ± 0.13
logMAR in unilateral cases, respectively. SOX2 mutations appear in
3/14 cases (15%).
Conclusions: In microphthalmic eyes primary IOL implantation
in congenital cataract resulted in a significant BCVA improvement
with minimal postoperative and no intraoperative complications.
Glaucoma and axial opacifications are well knowed long term
postoperative complications and children must be followed-up
regularly. Shorter axial lenght is a significat risk factor for postoperative complicatons. SOX2 mutation is found to be one of the
major causes of microphthalmus. Further studies of mutations
affecting lens membranes will give a better uderstanding of
congenital cataracts.
Commercial Relationships: Davide Borroni, None;
Araniko Pandey, None; Eriks Elksnis; Zita Krumina, None;
Ineta Orube, None; Elize A. Sture, None
Presentation Time: 3:45 PM–5:30 PMThe association between the
progression of rat sugar cataract and the levels of aldose reductase
in lens epithelium
Takeshi Tomomatsu, Yoshihiro Takamura, Takehiro Matsumura,
Shogo Arimura, Makoto Gozawa, Masaru Inatani. educational,
Yoshida, Japan.
Purpose: To examine the association between the levels of aldose
reductase (AR) in rat lens epithelial cells (LECs) and the progression
of the sugar cataract in streptozotocin (STZ) induced diabetic cataract
model rats with different levels of hyperglycemia.
Methods: Hyperglycemia was induced by the intraperitoneally
injection of STZ (0.1 mg/g body weight) in 3 weeks Sprague-Dawley
rats. Rats were divided into 3 groups in accordance with the amount
of blood sugar (BS), mild (200-300 mg/dl), moderate (300-400 mg/
dl), and severe (400 mg/dl over) BS groups. LECs with lens capsule
was obtained and the amount of AR was analyzed by Western blots.
The amount of polyol in whole lens was measured by liquid-gas
chromatography.
Results: There was a significant positive correlation between
the blood glucose level and the degree of the cataract (p=0.0015,
Spearman’s rank correlation), and AR inhibitor inhibited the
progression of cataract. The result of Western blot showed the levels
of AR expression of LECs was variables among individuals of rats
approximately 0.7~1.2 folds. A significant correlation between the
degree of cataract and AR levels was seen in the group of rats with
mild BS group (p=0.016), but not in those with moderate (p=0.853)
and severe (p=0.291) BS groups. Also, a significant correlation
between the levels of polyol and AR expression was seen in the group
of rats with mild BS group (p=0.046), but not in those with moderate
(p=0.971) and severe (p=0.873) BS group.
Conclusions: The increased level of AR expression was the risk
factor of the progression of sugar cataract under hyperglycemia.
Under the condition of severe hyperglycemia, polyol accumulation
and the formation of cataract were progressed regardless of AR
levels.
Commercial Relationships: takeshi tomomatsu;
Yoshihiro Takamura, None; Takehiro Matsumura, None;
Shogo Arimura, None; Makoto Gozawa, None; Masaru Inatani,
None
Distribution of γ-glutamyltranspeptidase, aldose reductase, and
biomarkers of oxidative stress in STZ-induced diabetic rat lens
Marlyn P. Langford1, Randa Eshaq2, Thomas B. Redens1,
Norman R. Harris2. 1Ophthalmology, Louisiana State University
Health Sciences Center, Shreveport, LA; 2Molecular & Cellular
Physiology, Louisiana State University Health Sciences Center,
Shreveport, LA.
Purpose: To investigate gamma-glutamyl transpeptidase (GGT, key
to glutathione recapture and cell transformation), aldose reductase
(AR, converts excess glucose to sorbitol) and oxidative stress
markers, [8-OHdG (8-hydroxy-2’-deoxyguanosine, oxidized DNA
marker) and annexin V (indicative of apoptosis)] expression in
streptozotocin (STZ)-induced diabetic cataractous and normal rat
lens.
Methods: Gross ocular examinations were performed and blood
glucose levels were determined on adult control and diabetic [STZinjected] Wistar rats. Bilateral eye enucleations were performed
post euthanasia at 8 weeks and the eyes placed in 70% ethanol.
Gross histopathology was determined on paraffin-embedded
sections stained with hematoxylin and eosin. DAPI-treated sections
were reacted with antibody to AR, GGT, 8-OHdG, and/or annexin
V, the corneal and lens distributions were visualized using the
immunofluorescent antibody method, and digital images captured for
comparative analysis.
Results: Gross cytopathological changes consistent with lens
epithelial cells disorganization and sub-capsular lens fiber cell
hyperplasia were noted in the cataractous lens of hyperglycemic STZinjected rats. In control rat lens, GGT was prominently expressed
by epithelial cells and diminished to undetectable levels within 1
mm (cortical zone) of the lens surface. GGT was not detected in
the lens core of control rat lens. AR and oxidized DNA (8-OHdG)
were detected in normal lens beneath the lens cortex within the lens
fibers (1 mm from the surface) and core. Weak annexin V reactivity
was detected in the lens epithelium. In the diabetic rat lens, GGT
expression in epithelial cells was decreased, while GGT expression
was increased on sub-capsular hyperplastic lens fiber cells. GGT was
not detected in the diabetic lens nucleus. Increased AR expression
and oxidized DNA (8-OHdG) were detected in the sub-capsular
hyperplastic lens fiber cells of diabetic rat lens. Oxidized DNA was
detected in annexin V-positive lens epithelial cells of some diabetic
lenses.
Conclusions: The sub-capsular cataractogenic changes in STZinduced hyperglycemic diabetic rats were associated with increased
expression of AR and GGT with oxidized DNA-positive hyperplastic
lens fiber cells. The results support hyperglycemia-induced lens fiber
cell dedifferentiation and oxidative epithelial cell death as evidenced
by annexin V expression.
Commercial Relationships: Marlyn P. Langford,
None; Randa Eshaq, None; Thomas B. Redens, None;
Norman R. Harris, None
Morphology and Organization of Anterior Fiber Ends in Lenses
from Streptozotocin-Induced Diabetic Rats
Kristin J. Al-Ghoul, Dushyant A. Sharma. Anatomy and Cell Biology,
Rush University Medical Center, Chicago, IL.
Purpose: Anterior and cortical cataracts typically manifest
subsequent to the development of a posterior subcapsular cataract in
streptozotocin (STZ)-induced diabetic rats. Our prior studies revealed
that abnormal anterior suture sub-branches formed in these lenses by
3 weeks post-induction. This investigation was conducted to evaluate
the overall organization and ultrastructural changes in elongating
fibers on the anterior surface of the lens during STZ-induced diabetes.
Methods: Male Wistar rats (125-150g; n=30) were randomized into
5 groups, four of which received a single 75 mg/kg intravenous dose
of STZ; the remaining group served as naïve controls. Animals were
euthanized at 1, 2, 3 and 4 weeks post-injection, blood glucose levels
(BGL) recorded and lenses removed, photographed and fixed for
structural evaluation via scanning electron microscopy (SEM).
Results: All naïve control lenses had normal BGL (avg.=114 mg/
dL), exhibited 3-branched “Y” suture patterns anteriorly and were
fully transparent. At time of sacrifice, BGL in experimental animals
was consistent with diabetes (avg.=360 mg/dL). SEM examination of
control lenses showed that anterior fiber ends were irregularly ovoid
with an ordered, tightly packed arrangement, and filopodia extended
in the general direction of migration towards sutures. Examination
of lenses from STZ-induced diabetics demonstrated progressive
changes in overall organization and ultrastructure of anterior fiber
ends. Specifically, by 2 weeks post-induction 50% of lenses had
regions of elongated, swirled fiber ends and occasional zones of fiber
disruption manifested as dilations of the extracellular space between
fibers. By three weeks after diabetic induction, all lenses displayed
regions of elongated, swirled fiber ends which frequently displayed
long disorganized filopodia. Localized areas of fiber breakdown were
common. Increasingly severe disruptions of fiber end arrangement
and morphology were noted at 4 weeks post-induction.
Conclusions: The data indicates that elongating fibers on the anterior
surface of the lens undergo a shift in their migration patterns which
manifests 2-3 weeks after diabetic induction. Because the changes
are delayed with respect to the posterior fiber ends, this suggests that
the anterior fiber ends are not as susceptible to hyperglycemia and/or
metabolic alterations during diabetes.
Commercial Relationships: Kristin J. Al-Ghoul, None;
Dushyant A. Sharma, None
Support: Mary Lou Bell McGrew Fund (Rush University), Chicago, IL.
High glucose inhibits autophagy in human lens epithelial cells
Xuhua Tan1, Chuan Chen2, 3, Yi Zhu2, 3, Yingfeng Zheng2,
Fu Shang2, Yizhi Liu2. 1cataract department, State Key Laboratory
of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yatsen University, Guangzhou, China; 2State Key Laboratory of
Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen
University, Guangzhou, China; 3department of molecular and cellular
pharmacology, Miller School of Medicine, University of Miami,
Miami, FL.
Purpose: Autophagy plays a key role in protein quality control,
which is critical for maintaining lens transparency. Autophagy also
is closely associated with glucose signaling pathway. Meanwihle,
diabetic patients are at higher risk for cataract formation at an earlier
age possibly due to hyperglycemia. However, the role of autophagy
in diabetic cataract development remains poorly defined. Here, we
tested the regulation of autophagy upon different environmental
glucose levels.
Methods: Human lens epithelial cell line SRA 01/04 were cultured
in dulbecco’s modified eagle medium with 5.5 mmol/L, 30 mmol/L
and 55 mmol/L glucose, respectively. mRNA and protein expression
levels of autophagy-related genes in cells were measured by real-time
PCR and western blot. Ten anterior capsule specimens of diabetic
cataract patients and ten age-matched control specimens were
obtained from continuous central curvilinear capsulotomy during
cataract surgery. mRNA and protein expression levels of autophagyrelated genes were measured by real-time PCR and whole mount
immunofluorescence staining.
Results: In SRA01/04 cells cultured with high glucose medium,
mRNA level of LC3B, Beclin1, ULK1 and FYOC1 were
downregulated and protein expression level of LC3B, Beclin1
are reduced compared with cells treated with normal glucose
concentration. Consistently, in lens epithelial cells from diabetic
patients, mRNA level of LC3B, Becliln1, ULK1 and FYCO1 were
downregulated and protein expression level of LC3B and Beclin1
were reduced.
Conclusions: High environmental glucose inhibits autophagy in
human lens epithelial cells. This indicates that autophagy may
have a role in diabetic cataract pathogenesis by controlling protein
degradation.
Commercial Relationships: xuhua tan, None; Chuan Chen, None;
Yi Zhu, None; Yingfeng Zheng; Fu Shang, None; Yizhi Liu, None
Radiation cataract in an outbred population of mice following
gamma or high-LET irradiation
Norman J. Kleiman1, Eric Hall2, Mike M. Weil3, Catherine Schmidt4,
Elijah Edmondson5, Adam King4. 1Environmental Health Sciences,
Columbia University, New York, NY; 2Center for Radiological
Research, Columbia University, New York, NY; 3Environmental &
Radiological Health Sciences, Colorado State University, Ft. Collins,
CO; 4Clinical Sciences, Colorado State University, Ft. Collins, CO;
5
Dept. of Microbiology and Immunology, Colorado State University,
Ft. Collins, CO.
Purpose: This study was designed to determine the influence of
genetic background on radiation cataract after either HZE ion or
gamma irradiation. Most radiation cataract rodent models utilize
inbred strains with limited genetic heterogeneity. The availability
of diversity outbred heterogeneous mouse stocks combined with
high-throughput single nucleotide polymorphism (SNP) genotyping,
facilitates new approaches to study radiation cataract in genetically
heterogeneous populations. These tools should permit better analysis
of radiation-induced gene-environment interactions and better models
the genetic diversity found in human populations.
Methods: 1,800 HS/Npt 2 month old mice of both sexes were
irradiated with 0.4 Gy of 240 MeV/n 28Si, 600 MeV/n 56Fe ions, or
3 Gy 137Cs gamma rays, or sham irradiated controls. As part of a
larger study examining carcinogenesis, cognitive deficits or ocular
defects, the eyes of mice were monitored by dilated slit lamp exam
and their vision by Virtual Optomotry for up to two years of age.
Lens opacities were staged by modified Merriam-Focht scoring. Each
mouse was also genotyped for 78,000 SNPs.
Results: Radiation of both qualities increased cataract development
with Hazard Ratios of ~2.3 for γ and ~2.6 for HZE. HZE irradiated
mice are at increased risk over gamma irradiation. Cataract
susceptibility loci in these heterogeneous mice are being mapped
to determine overlap, if any, with either cognitive or carcinogenic
endpoints. The SNP genotype data is being used to localize the
genetic factors that predispose individual mice to either spontaneous
ocular defects or radiation-induced posterior subcapsular lens
changes. Time of onset of lens opacification and final lens opacity
severity score demonstrate strong family-specific susceptibility. No
gender specific preference for lens opacity was noted.
Conclusions: There are strong family-based genetic determinants
that influence predisposition to radiation cataract in an outbred mouse
population irradiated with either low- or high-LET radiation. There
does not appear to be any gender based predisposition within this
cohort. The availability of new analytical tools permits comparison of
these findings with genetic loci associated with specific carcinogenic
or cognitive endpoints in these same mouse populations.
Commercial Relationships: Norman J. Kleiman, None;
Eric Hall; Mike M. Weil, None; Catherine Schmidt, None;
Elijah Edmondson, None; Adam King, None
Support: NASA NNX12AB54G
UVR- B irradiation of one eye stimulates immunological crosstalk towards the unexposed contralateral eye in a mouse model
Janine Gross1, Linda M. Meyer1, 2, Carl-Ludwig Schönfeld2, 3,
Frank G. Holz1, Alfred R. Wegener1. 1Ophthalomology, University
Bonn, Bonn, Germany; 2Herzog Carl Theodor Eye Clinic, Munich,
Germany; 3Eye clinic Ludwig-Maximilian university, Munich,
Germany.
Purpose: Investigation of unilateral UVR-B irradiation effects to
the exposed eye in comparison to the unexposed contralateral eye in
vivo in the mouse model. Characterization of inflammatory reactions
which lead to cataract formation in the unexposed eye with a certain
latency period. Identification of immunological pathways responsible
for propagation of the radiation effect to the unexposed eye.
Methods: Six-week-old C57Bl/6 mice (pigmented) and ABCA4
mice (albino) were unilaterally exposed in vivo to a triple threshold
dose (9,4 kJ/m2 pigmented) and double threshold dose (6,5 kJ/m2
albino) of UVR-B. The other eye was covered with aluminium foil.
UVR-B irradiation in the 300-nm wavelength region (UVR-B peak
at 312nm) was performed in mydriasis using a Bio-Spectra system
(Vilber Lourmat, Germany). After a latency period of 3 and 7 days
following UVR-B exposure, morphological changes in the lenses
were photographed with a Leica dark-field microscope. Thereafter
lenses were fixed in 4 % Paraformaldehyde, embedded in paraffin,
sectioned and stained with fluorescence coupled antibodies for
substance P receptor, NKR-1 and DAPI for cell nuclei. All animal
experiments were done according to the regulations of the German
Tierschutzgesetz and the ARVO declaration of the use of animals in
eye and vision research.
Results: UVR-B exposure induced corneal edema anterior
subcapsular cataract in the exposed eye after a latency period of 3
days. At day 7 a triangular-shaped opacity had developed in the area
of anterior suture. After a latency period of 3 to 7 days, unexposed
lenses showed opacities in the lens nucleus and also diffuse opacities
in the anterior superficial suture of the lens. Histological examination
revealed positive staining for NK-1 receptor in the corneal
epithelium, the nuclear bow epithelium of the lens, the ciliary body
epithelium and in the inner plexiform layer of the retina in pigmented
animals. The albino mice additionally showed positive staining in the
iris vessels which could be due to the absence of pigmentation.
Conclusions: Unilateral UVR-B exposure of the eye affects the
unexposed eye in a sympathetic reaction. To explain the inflammation
in the contralateral eye, the role of substance p, and other neuroinflammatory peptides needs further investigation.
Commercial Relationships: Janine Gross, None; Linda M. Meyer,
None; Carl-Ludwig Schönfeld; Frank G. Holz, Novartis (C),
Genentech (C), Roche (C), Heidelberg Engineering (C), Bayer
Healthcare (C), Allergan (C), Alcon (C); Alfred R. Wegener, None
Support: DFG WE 1303/6-1; AOBJ: 612904
Hyperexpression of fatty acid binding protein 5 in atopic cataract
Toshiaki Hirakata1, Kanae Kobayashi-Takakuwa1, Toshinari Funaki1,
Nobuyuki Ebihara2, Akira Matsuda1. 1Ophthalmology, Juntendo
University School of Medicine, Bunko-ku, Japan; 2Ophthalmology,
Juntendo Urayasu Hospital, Chiba, Japan.
Purpose: The molecular mechanism of atopic cataract formation
is still ill defined. To clarify pathophysiology of atopic cataract, we
carried out genome wide gene expression analysis.
Methods: Two anterior capsules were obtained from atopic cataract
patients with subcapsular cataract formation. Total RNA was
extracted and genome wide gene expression analysis was carried
out using Agilent SurePrint Human Gene Expression array. Anterior
capsular tissue obtained from senile cataract patients were used as
control. To confirm the results of gene array experiments, realtime
PCR analysis was performed using 7 anterior capsules from atopic
cataract patients and 5 from control patients.
Results: The results of genomewide gene expression analysis showed
12 genes are hyperexpressed (more than 5 folds) in the anterior
capsule of atopic cataract patients compared to the control. Among
the 12 genes, fatty acid binding protein 5 (FABP5) gene expression
is increased (36 fold, compared to the controls) in the replicative
samples by realtime PCR analysis.
Conclusions: FABP5 gene, which have essential roles for lipid
metabolism, may have some relations to the pathophysiology of
atopic cataract.
Commercial Relationships: Toshiaki Hirakata, None;
Kanae Kobayashi-Takakuwa, None; Toshinari Funaki, None;
Nobuyuki Ebihara, None; Akira Matsuda, None
Differential expression of Tumoral Necrosis Factor Receptor in
different types of cataract.
Eduardo S. Arellano Arias, Atzin Robles-Contreras. Fundacion
Hospital Nuestra Señora de la Luz, Mexico Distrito Federal, Mexico.
Purpose: to compare the presence of the Tumoral Necrosis Factor
receptor (TNFR) in lenses with senile, traumatic and diabetic
cataract.
Methods: Lenses with clinical diagnosis of senile, traumatic
and diabetic cataract were used to run the study. Material was
homogenized and processed to quantify the total amount proteins.
Dilutions were made in order to obtain the same amount of total
proteins in each sample and ELISA was used for TNFRSF1A
quantification. To analyze the data distribution and for group
comparison the D’Agostino & Pearson and the Kruskall Wallis test
were used respectively.
Results: An average concentration of TNRF of 172.7±124.5 pg/ml in
senile cataracts was found. In traumatic cataracts, the TNFR average
was 409.8±124.5pg/ml and in diabetic cataracts 457.9±212.1 pg/ml.
A statistically significant difference between senile and traumatic
cataract (p=0.0051) and between senile and diabetic cataract
(p=0.0067) was found. There was no statistical difference between
traumatic and diabetic cataract (p=0.454).
Conclusions: Differential expression in TNFR levels was found in
senile cataracts as compared with traumatic and diabetic cataracts.
This overexpression in TNFR could be associated with increased
levels of TNF which would imply an inflammatory mechanism in
the development of traumatic and diabetic cataracts. This could also
imply a role of apoptosis in the events that lead to the development of
this pathology.
Commercial Relationships: Eduardo S. Arellano Arias, None;
Atzin Robles-Contreras, None
Abnormal anterior lens epithelium in retinitis pigmentosarelated cataract – scanning and transmission electron microscopy
study Hawlina M, MD, PhD 1, Drašlar K, PhD 2, Hvala A, PhD
3
, Andjelic S, PhD1 1Eye Hospital, University Medical Centre,
Ljubljana, Slovenia 2Department of Biology, Biotechnical Faculty,
University of Ljubljana, Ljubljana, Slovenia 3Department of
Pathology, Medical Faculty, University of Ljubljana, Ljubljana,
Slovenia
Marko Hawlina. Eye Hospital, University Medical Centre Ljubljana,
Ljubljana, Slovenia.
Purpose: In retinitis pigmentosa (RP) patients, lens opacity usually
develops in the posterior pole and may cause disproportionate
functional symptoms requiring cataract operation. The reason
of development of this peculiar type of cataract is at present
unknown. To investigate possible structural reasons, we studied the
ultrastructure of the lens epithelium of RP patients.
Methods: Seven anterior lens capsules from five patients patients
with sporadic RP (aLC: basement membrane and associated lens
epithelial cells, LECs) were obtained from cataract surgery and
prepared for both scanning and transmission electron microscopy
(SEM and TEM).
Results: Both SEM and TEM show a number of abnormal features
in the anterior lens epithelium of cataract patients with RP. The
abnormalities appear mainly as holes, thinning and degradation of the
epithelium, with the dimensions up to 50 um (Fig. 1). Another type
of abnormalities such as cracks at the cell border (Fig. 2) were seen
between adjacent LECs where lateral connections are absent, with
dimensions 0.1-2 um x up to 10 um.
Conclusions: Abnormal structural features in the anterior lens
epithelium were found in RP-associated cataract. This may affect
the patency and transport function of the lens epithelium and cause
water influx and clouding along the water clefts leading towards the
posterior pole. We suggest that the lens epithelium has a role in the
development of the cataract in RP patients.
Commercial Relationships: Marko Hawlina, None
Support: ARRS P3-0333
Imaging of crystalline lens using a new anterior segment optical
coherence tomography
Haruhiro Mori, Yuta Ueno, Akari Terauchi, Takahiro Hiraoka,
Tetsuro Oshika. University of Tsukuba, Tuskuba, Japan.
Purpose: Anterior segment optical coherence tomography (ASOCT) is widely used to image anterior segments of the eye, such as
cornea, anterior chamber, angle, and filtering bleb after glaucoma
surgery. However, it is difficult to obtain a clear image of the whole
crystalline lens using conventional AS-OCT due to narrow imaging
depth. A newly developed AS-OCT (SS-2000, Tomey) has a larger
imaging depth, allowing an entire image of anterior segment from
anterior surface of the cornea to posterior surface of the crystalline
lens to be simultaneously obtained. In this study, we examined
patients with cataract using SS-2000 and Scheimpflug camera (EAS1000, NIDEK), and compared their images of the crystalline lens.
Methods: Seventy-nine eyes of 41 patients (15 men and 26 women)
with cataract ranging in age from 47 to 89 years (71.0 ± 8.2, mean ±
standard deviation) were examined. Various types of cataract, such
as nuclear, cortical, posterior subcapsular, and mature cataract were
included. Tomographic images of crystalline lens were obtained using
SS-2000 and EAS-1000 under pupillary dilatation. Two systems were
compared in terms of the image quality of lens opacity and detection
rate of the posterior capsule.
Results: The measurement results of lens nucleus intensity was
generally lower with SS-2000 than with EAS-1000. Cortical and
posterior subscapular opacities appeared as high intensity areas
both with SS-2000 and EAS-1000, but there were less halation and
backward shadow seen in SS-2000 images especially in eyes with
calcification of the anterior capsule. The detection rate of posterior
capsule was significantly higher with SS-2000 (77 eyes, 97.5%) than
with EAS-1000 (21 eyes, 28.4%) (P < 0.05).
Conclusions: The SS-2000 AS-OCT system was very useful for
obtaining an entire image of the crystalline lens, and appeared more
beneficial in the evaluation of cortical and posterior subcapsular opacities
than the EAS-1000 camera system. However, the intensity of nuclear
opacities tended to be lower with SS-2000 than with EAS-1000.
Commercial Relationships: haruhiro mori; Yuta Ueno,
Tomey corporation (F); Akari Terauchi, Tomey corporation (F);
Takahiro Hiraoka, Tomey corporation (F); Tetsuro Oshika, Tomey
corporation (F)
Support: Tomey corporation
Evaluation of waterclefts by anterior segment OCT
Hisanori Miyashita, Hiromi Osada, Eri Shibuya, Naoki Tanimura,
Teppei Shibata, Kazuyuki Sasaki, Eri Kubo, Hiroshi Sasaki.
Kanazawa Medical University, Kahoku, Japan.
Purpose: Waterclefts (WC), which develop by cleavage at the
Y suture and deteriorate visual function, are sometimes difficult
to detect by transillumination image. In this study, we compared
the detection rate between anterior segment optical coherence
tomography (OCT) and Scheimpflug slit image.
Methods: Of participants of Monzen Eye Study, an epidemiological
study for ocular disease in residents of Monzen town, Ishikawa, 134
eyes of 70 subjects (67.8±10.3 yrs.) were examined under maximum
mydriasis in November 2015. Using slit lamp examination, cataracts
were classified by one doctor. Lens images were obtained by both
anterior segment OCT (CASIA2, Tomey) and anterior segment
analysis system (EAS-1000, Nidek), and WC were diagnosed from
vertical/horizontal sectional views in the central 3-mm diameter area
of the pupil. The rate of cases where it was possible to image the
posterior capsule was included too. Eyes with an intraocular lens
were excluded. Statistical analysis was performed using chisquare test.
Results: WC were present in 48 of the 134 eyes (35.8%).
The detection rate of WC with CASIA2, 41 eyes (85.4%) was
significantly higher than that with EAS-1000, 28 eyes (58.3%)
(p<0.01). The posterior capsule were observed in 134 eyes (100%) by
using CASIA2, significantly higher than in 60 eyes (44.8%) by using
EAS-1000 (p<0.001).
Conclusions: Objective evaluation of WC, a lenticular change that
affects visual function, is highly important. By using anterior segment
OCT CASIA2, it is possible to image the posterior segment of the
lens, which is effective to clearly detect and diagnose WC.
Commercial Relationships: Hisanori Miyashita, None;
Hiromi Osada; Eri Shibuya, None; Naoki Tanimura, None;
Teppei Shibata, None; Kazuyuki Sasaki, None; Eri Kubo, None;
Hiroshi Sasaki, None
A comparative study of optical coherence tomography and slitlamp based grading of cataract
Aman-Deep S. Mahil, Kathryn Saunders, Patrick Richardson,
Julie-Anne Little. Biomedical Sciences Research Institute, Ulster
University, Coleraine, United Kingdom.
Purpose: Established methods of grading cataract are susceptible
to error due to their subjective nature as well as variation in slit-
lamp settings during assessment. Furthermore, grading systems
such as the Lens Opacities Classification System III (LOCS III)
are only applicable to age-related forms of the condition. Optical
coherence tomography (OCT) offers the potential to provide an
objective method of imaging and grading all forms of cataract. An
observational clinical study was performed to compare anterior
segment OCT imaging with traditional, slit-lamp based grading.
Methods: Crystalline lens images of 60 eyes from 38 adults aged 50
to 79 years (mean 62.97+/-9.99) were captured using a Nikon FS-3
slit-lamp photo-biomicroscope and a Zeiss Visante anterior segment
OCT. Prior to imaging, participants were assessed for habitual
visual acuity (logMAR), contrast sensitivity (Pelli-Robson) and
straylight scatter (Oculus C-Quant). Pupils were then dilated with 1%
tropicamide to obtain optimum images of the crystalline lens. The
slit-lamp images were graded for age-related cataract (nuclear colour
and opalescence) using the LOCS III. Raw OCT data were analysed
in MATLAB to determine a pixel intensity ratio for the nucleus of
each crystalline lens (see figure). Linear regression compared LOCS
III nuclear opalescence and nuclear colour scores to OCT pixel
intensity ratios.
Results: Age-related nuclear cataract was the predominant cataract
type, with LOCS III mean scores of 2.04+/-0.63 for nuclear
opalescence and 1.65+/-0.71 for nuclear colour. Cortical and
posterior subcapsular cataract were present at low levels (0.32+/0.51; 0.12+/-0.12 respectively). Mean OCT nuclear pixel intensity
ratio was 1.077+/-0.04. Regression analyses revealed significant
relations between pixel intensity ratio and nuclear opalescence
(F(1,58)=8.24, p<0.006) as well as pixel intensity ratio and nuclear
colour (F(1,58)=4.37, p<0.041).
Conclusions: OCT can provide an objective method of imaging and
grading the severity of cataract. OCT may be an effective means of
profiling cataract in populations who do not exhibit typical agerelated forms of crystalline lens opacities.
Panel A. Raw OCT image of the anterior crystalline lens. Panels
B-E. Images depicting the selection of the anterior chamber and
nucleus. The pixel intensity ratio is the quotient of mean nuclear pixel
intensity (E) divided by mean anterior chamber pixel intensity (C).
Commercial Relationships: Aman-Deep S. Mahil, None;
Kathryn Saunders, None; Patrick Richardson, None; JulieAnne Little, None
Support: Department for Employment & Learning, Northern Ireland,
UK
Dual wavelength TD-PCI-system for Cataract Classification of
Intraocular Lenses
Haroun Al-Mohamedi, Theo Oltrup, Guido Mieskes, Ismael Kelly,
Martin. Leitritz, Thomas Bende. Dept. of Ophthalmology, University
Eye Hospital, Tuebingen, Tuebingen, Germany.
Purpose: To measure and characterize the size and density of
particles inside an intraocular lens(IOL) using a Human Model Eye.
Methods: A time domain partial coherence interferometry system
(TD-PCI) based on two light sources at 820 nm ,673 nm and a
piezoelectric motor (PI-type M-663 Compact LinearTranslation) with
a spatial accuracy of up to 0.1 μm.
A SLD (type EXS8310, λ = 820 nm, Exalos, Switzerland) und a SLD
(type SLD-261-MP1, λ = 673 nm, Superlum, Ireland) were used as
light sources. With a fiber coupler both light sources coming into the
measurement system, so that an equal profile for both light sources
was achieved.
As a model for cataract inside the IOL, microparticles of 1 and 3
microns, are randomly distributed with different densities (0-800.000
beads/IOL) were by Human Optics AG prepared.
For detecting the transmitted scattered light of the IOL a CCD camera
is used. the point-spread functions (PSF’s) are analyzed.
Influence of density of particles site on Refractive indices inside the
IOL is evaluated by the signal processing of the TD-PCI-system.
Results: The Analysis of the obtained PSF’s shows that the PSF is
influenced by the size and density of the particles. For 3 microns
particles both radial profiles of PSF’s have in our setup a crossing
point between radial profiles at 1.5 mm from the center. the crossing
point of the clear intraocular lens was at 5,5mm from the center.
The density of the particles is linearly correlated with the amplitude
of the TD-PCI-signal.
High densities of particles inside the IOL had to a change further
focus length.
For the highest density of the 3 microns particles an increase of the
focal length of 30µm was found.
Conclusions: The combined setup of the two wavelengths TDPCI-system shows a significant improvement for detecting size and
density of particles inside an IOL of Human Eye. This may be used
for an objective classification of cataract.
Commercial Relationships: Haroun Al-Mohamedi, None;
Theo Oltrup, None; Guido Mieskes, None; Ismael Kelly, None;
Martin. Leitritz, None; Thomas Bende, None
Visual function of eyes with waterclefts
Naoki Tanimura, Eri Shibuya, Mai Kita, Ayako Okamoto,
Norihiro Mita, Natsuko Hatsusaka, Teppei Shibata, Shinsuke Shibata,
Eri Kubo, Hiroshi Sasaki. Ophthalmology, Kanazawa Medical
University Hospital, Kahoku, Japan.
Purpose: To examine the impact of waterclefts (WC) on visual
function.
Methods: We studied 42 eyes of 30 patients (age 69.4±7.5 yrs) with
WC cataract and no other eye disease among patients of Kanazawa
Medical University Hospital, October 2013 through July 2015. One
examiner classified cataracts by KMU classification as WC central
type (any WC in the central 3-mm diameter) and WC peripheral
type (WC outside the 3-mm diameter) and compared these eyes
with 42 transparent lens eyes of participants of Monzen Eye Study
in 2013 as controls (age 57.2±8.7 yrs). We measured best-corrected
visual acuity (BCVA), 25％ contrast visual acuity (CVA) under 4
illumination conditions (DAY, DAY+G, EVE, EVE+G), total higher
order aberration (tHOA) in 4 mm and 6mm entrance pupils with KR9000W (TOPCON), and forward light scattering (FLS) with C-Quant
(OCULUS), back light scattering (BLS) as peak height of anterior
embryonal nucleus with EAS-1000 (NIDEK).
Results: BCVA in WC eyes (0.13±0.22logMAR) was significantly
lower than in control eyes (-0.13±0.07logMAR) (p<0.001). CVA in
WC eyes was significantly lower than in control eyes under the 4
illumination conditions (p<0.001), and CVA in WC central type eyes
was significantly lower than in WC peripheral type. FLS in WC eyes
was significantly higher than in control eyes, and significantly higher
in WC central than in WC peripheral type. tHOA was significantly
increased in WC eyes (p<0.05) with that in WC central significantly
greater than that in WC peripheral type eyes (p<0.05). There was
no difference in BLS among three groups. In multiple regression
analysis of WC eyes, BCVA showed significant correlations with
tHOA, FLS, BLS (r=0.4658, p<0.05) showing the most significant
correlation with tHOA.
Conclusions: Waterclefts have a significant impact on visual function
due to increase in tHOA, FLS and BLS, especially by increasing
tHOA.
Commercial Relationships: Naoki Tanimura, None;
Eri Shibuya, None; Mai Kita, None; Ayako Okamoto, None;
Norihiro Mita; Natsuko Hatsusaka, None; Teppei Shibata, None;
Shinsuke Shibata, None; Eri Kubo, None; Hiroshi Sasaki, None
Influence of age on visual function of eyes with cataract
Hiroshi Sasaki1, Mai Kita1, Hisanori Miyashita1, Naoki Tanimura1,
Hiromi Osada1, 2, Teppei Shibata1, Yoriko Takahashi1,
Shinsuke Shibata1, Eri Kubo1. 1Department of Ophthalmology,
Kanazawa Medical University, Kahoku, Japan; 2Ophthalmology,
Anamizu General Hospital, Anamizu, Japan.
Purpose: To investigate a correlation between visual function and
age in eyes with cataracts per opacity type.
Methods: Of participants of Monzen Eye Study, an epidemiological
study of ocular disease in residents of Monzen town, Ishikawa,
and patients for cataract surgery at Kanazawa Medical University
Hospital from 2006 to 2013, 1008 eyes of 886 subjects were
examined for cortical cataract with central opacity (COR(CEN+)),
cortical cataract without central opacity (COR(CEN-)), nuclear
cataract (NUC), posterior sub-capsular cataract (PSC), retrodots
(RD), waterclefts in the central area (WC(CEN+)), and the peripheral
area (WC(CEN-)). Cases with ocular disease except for refractive
error were excluded. Contrast visual acuity (CA) was measured by
CAT2000 (NEITZ) under 25% contrast of day and evening light.
Ocular total higher-order aberration (HOA) and spherical aberration
were examined by Wavefront Analyzer (KR-9000PW: TOPCON),
and axial length by IOL-Master (ZEISS). One examiner classified
COR, NUC and PSC by WHO system and RD and WC by Kanazawa
Medical University system with maximum pupil dilatation.
Results: CA under 25% daylight was decreased with age in eyes with
COR(CEN-), Grade 1-2 COR(CEN+), and Grade 1-2 RD (p<0.05).
CA under 25% evening light in younger- was worse than that in
elderly-age eyes with Grade 1 NUC (p<0.05). In eyes with Grade 1
NUC, there were a positive correlation between age and spherical
aberration and a negative correlation between age and axial length,
both significantly (p<0.05). In PSC and both of WC(CEN-/+), there
was no significant correlation between age and CA under 25% day/
evening light. With aging, CA under 25% daylight decreased most in
eyes with Grade 1 RD.
Conclusions: Visual function was decreased with aging in eyes with
the same grade of COR and RD, and was worse in younger age with
NUC. It is necessary to consider the influence of age for indication of
cataract surgery.
Commercial Relationships: Hiroshi Sasaki; Mai Kita, None;
Hisanori Miyashita, None; Naoki Tanimura, None; Hiromi Osada,
None; Teppei Shibata, None; Yoriko Takahashi, None;
Shinsuke Shibata, None; Eri Kubo, None
A study of the dynamics of the relationship of the lens with blood
glucose levels and HbA1c in patients with insulin dependent
Diabetes Mellitus type 2
Lydia A. Mineeva1, Irina G. Slezkina2, Leonid Balashevich3,
Leonid Shubin4, Andrei Kabanov5. 1Department of Ophthalmology,
Yaroslavl State Medical University, Yaroslavl, Russian Federation;
2
Ophthalmology Section, Yaroslavl Regional Hospital, Yaroslavl,
Russian Federation; 3Eye Microsurgery Complex named by S.
Fyodorov, St.Petersburg, Russian Federation; 4Anatomopathology,
Yaroslavl State Medical University, Yaroslavl, Russian Federation;
5
Clinical Pharmacology, Yaroslavl State Medical University,
Yaroslavl, Russian Federation.
Purpose: We have previously shown that the normalization of blood
glucose, in the development of diabetic cataract, may improve the
lens NO but does not change the NC and P and does not stop the
existing changes C. HbA1c is a more sensitive indicator than blood
glucose, but eye structures react to it differently. The aim of this work
is to study the dynamics of the relationship of the lens with blood
glucose levels and HbA1c in patients with insulin dependent Diabetes
Mellitus (DM) type 2 in a subcompensation phase.
Methods: Ophthalmologic monitoring lasted 3 years and insulin
therapy for 6 years. A group consists of 32 patients (64 eyes):
84.4% females and 15.6% males with DM type 2 without severe
complications and concomitant eye pathology at age of 60.4±5.3.
The lens was estimated by LOCS III. Blood glucose level was
significantly decreased, and HbA1c levels remained almost constant.
Results: A significant negative correlation (Spearman R=-0.31;
p=0.018) between glucose and NO was found only on 4th visit. With
HbA1c and the lens components (nuclear opalescence (NO), nuclear
color (NC), cortical cataract (C), posterior subcapsular cataract
(P)), a significant correlation was found in all 4 visits. On the first
visit a positive correlation was between HbA1c and C OD (R=0.27;
p=0.013) and P OS (R=0.32; p=0.007) i.e. a decrease in HbA1c lead
to a higher clarity of C and P. At 4-th visit a negative correlation
was for NO OD (R=-0.3; p=0.021) and C OS (R=-0.33; p=0.014);
reducing of HbA1c lead to a lower clarity of NO and C.
Conclusions: HbA1c is a marker and a trigger of possible changes
in the lens in patients with DM type 2 with prolonged insulin
therapy. HbA1c is more effective indicator to track changes in the
eye dynamics in these patients. Changing of a positive correlation
between HbA1c and C at the beginning of the study to a negative
one at the end indicates to disruption of the lens compensation and
does not stop the negative changes in the index C of the lens even at
reducing of HbA1c.
Commercial Relationships: Lydia A. Mineeva, None;
Irina G. Slezkina, None; Leonid Balashevich, None;
Leonid Shubin, None; Andrei Kabanov, None

Session 277 Cataractogenesis

Transcription

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