Cataract Research Research Articles

Drugs associated with cataract formation represent an unmet need in cataract research.

Decreased light transmittance through the ocular lens, termed cataract, is a leading cause of low vision and blindness worldwide. Cataract causes significantly decreased quality of life, particularly in the elderly. Environmental risk factors, including aging, UV exposure, diabetes, smoking and some prescription drugs, are all contributors to cataract formation. In particular, drug-induced cataract represents a poorly-addressed source of cataract. To better understand the potential impact of prescription drugs on cataract, we analyzed publicly-available drug prescriptions data from the Australian Pharmaceutical Benefits Scheme. The data was analyzed for the 5-year period from July 2014 to June 2019. Analyses included the number of prescriptions for each drug, as well as the associated government and total prescription costs. The drugs chosen for analysis belonged to any of four broad categories—those with known, probable, possible or uncertain association with cataract in patients. The analyses revealed high prescription rates and costs for drugs in the Known category (e.g., steroids) and Possible category (e.g., psychotropic drugs). Collectively, these data provide valuable insights into specific prescription drugs that likely contribute to the increasing annual burden of new cataract cases. These data highlight the need—as well as new, stem cell-based opportunities—to elucidate molecular mechanisms of drug-induced cataract formation.

Investigation of the scattering and attenuation properties of cataracts formed in mouse eyes with 1060-nm and 1310-nm swept-source optical coherence tomography.

Cataracts are the leading cause of blindness worldwide. Here we propose optical coherence tomography (OCT) as a quantitative method for investigating cataracts. OCT provides volumetric and non-invasive access to the lens and makes it possible to rapidly observe the formation of opacifications in animal models such as mice. We compared the performance of two different wavelengths – 1060 nm and 1310 nm – for OCT imaging in cataract research. In addition, we present multi-contrast OCT capable of mapping depth-resolved scattering and average anterior cortical attenuation properties of the crystalline lens and quantitatively characterize induced cataract development in the mouse eye. Lastly, we also propose a novel method based on the retinal OCT projection image for quantifying and mapping opacifications in the lens, which showed a good correlation with scattering and attenuation characteristics simultaneously analyzed during the process of cataract formation in the lens.

Rasch Validation of the VF-14 Scale of Vision-Specific Functioning in Greek Patients

The Visual Functioning-14 (VF-14) scale is the most widely employed index of vision-related functional impairment and serves as a patient-reported outcome measure in vision-specific quality of life. The purpose of this study is to rigorously examine and validate the VF-14 scale on a Greek population of ophthalmic patients employing Rasch measurement techniques. Two cohorts of patients were sampled in two waves. The first cohort included 150 cataract patients and the second 150 patients with other ophthalmic diseases. The patients were sampled first while pending surgical or other corrective therapy and two months after receiving therapy. The original 14-item VF-14 demonstrated poor measurement precision and disordered response category thresholds. A revised eight-item version, the VF-8G (‘G’ for ‘Greek’), was tested and confirmed for validity in the cataract research population. No differential functioning was reported for gender, age, and underlying disorder. Improvement in the revised scale correlated with improvement in the mental and physical component of the general health scale SF-36. In conclusion, our findings support the use of the revised form of the VF-14 for assessment of vision-specific functioning and quality of life improvement in populations with cataracts and other visual diseases than cataracts, a result that has not been statistically confirmed previously.

5‑Nitro‑2‑(3‑phenylpropylamino) benzoic acid induces apoptosis of human lens epithelial cells via reactive oxygen species and endoplasmic reticulum stress through the mitochondrial apoptosis pathway.

Cataracts have a high incidence and prevalence rate worldwide, and they are the leading cause of blindness. Lens epithelial cell (LEC) apoptosis is often analysed in cataract research since it is the pathological basis of cataracts, except for congenital cataract. Chloride channels are present in ocular tissues, such as in trabecular cells, LECs and other cells. They serve an important role in apoptosis and participate in endoplasmic reticulum (ER) stress and oxidative stress. However, their role in the apoptosis of LECs has not been discussed. The present study examined the effects of the chloride channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) in human LECs (HLECs) to elucidate the role of NPPB in HLECs and investigate the role and mechanism of chloride channels in cataract formation. HLECs were exposed to NPPB. Cell survival rate was evaluated using Cell Counting Kit-8 assays. Oxidative stress was detected as reactive oxygen species (ROS) in cells by using a ROS assay kit. Apoptosis was examined by assessing mitochondrial membrane potential and using a JC-1 assay kit, and western blot analysis was performed to measure the expression levels of mitochondrial-dependent apoptosis pathway-associated proteins. ER stress was evaluated by determining the intracellular calcium ion fluorescence intensity, and western blot analysis was performed to measure ER stress-associated protein expression. The results revealed that NPPB treatment decreased the viability of HLECs and increased apoptosis. Additionally, NPPB increased intracellular ROS levels, as well as the number of JC-1 monomers and the protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X and cleaved caspase-3, and decreased Bcl-2 protein expression. NPPB increased intracellular calcium ions, the protein expression levels of activating transcription factor 6, JNK, C/EBP homologous protein and caspase-12, and the phosphorylation of protein kinase R-like endoplasmic reticulum kinase. N-acetylcysteine and 4-phenylbutyric acid inhibited NPPB-induced oxidative stress, ER stress and apoptosis. Therefore, NPPB treatment decreased cell viability and promoted apoptosis of HLECs via the promotion of oxidative and ER stress.

Recent Advances in Cataract Research Using D-Amino Acids as a Molecular Marker

Recent Advances in Cataract Research Using D-Amino Acids as a Molecular Marker

Increasing protected data accessibility for age-related cataract research using a semi-automated honest broker

Ophthalmology researchers are becoming increasingly reliant on protected data sets to find new trends and enhance patient care. However, there is an inherent lack of trust in the current healthcare community ecosystem between the data custodians (i.e., health care organizations and hospitals) and data consumers (i.e., researchers and clinicians). This typically results in a manual governance approach that causes slow data accessibility for researchers due to concerns such as ensuring auditability for any authorization of data consumers, and assurance to ensure compliance with health data security standards. In this paper, we address this issue of long-drawn data accessibility by proposing a semi-automated “honest broker” framework that can be implemented in an online health application. The framework establishes trust between the data consumers and the custodians by:
 1. improving the eiciency in compliance checking for data consumer requests using a risk assessment technique;
 2. incorporating auditability for consumers to access protected data by including a custodian-in-the-loop only when essential; and
 3. increasing the speed of large-volume data actions (such as view, copy, modify, and delete) using a popular common data model.
 Via an ophthalmology case study involving an age-related cataract research use case in a community cloud testbed, we demonstrate how our solution approach can be implemented in practice to improve timely data access and secure computation of protected data for ultimately achieving data-driven eye health insights.

Cataract Research for Ophthalmologists

Cataract Research for Ophthalmologists

Attenuation of oxygen fluctuation-induced endoplasmic reticulum stress in human lens epithelial cells.

Cataractogenic stresses are associated with the induction of endoplasmic reticulum (ER) stress. However, little is known about oxygen (O2)-induced ER stress in the lens. Cataract research has focused on elevated levels of O2 in lens epithelial cells (LECs). Excessive levels or a lack of O2 are known to induce ER stress whereas chronic ER stress activates the unfolded protein response (UPR). The present study investigated the hypothesis that the fluctuation of O2 levels induces a UPR, and may be controlled by maintaining human LECs (hLECs) in a specific concentration of O2. Human LECs were cultured in different atmospheric levels of O2. Hypoxic conditions were determined by the level of hypoxia-inducible factor (HIF)-1α. 2',7'-Dichlorodihydrofluorescein diacetate and ethidium homodimer-1 staining were conducted to detect reactive oxygen species (ROS) and cell death, respectively. Protein blot analyses were performed with antibodies specific to antioxidant and UPR-specific proteins. Reverse transcription-quantitatative polymerase chain reaction assays were performed to quantify the mRNA levels of activated NF-E2-related factor 2 (Nrf2) and kelch-like ECH-associated protein 1 (Keap1). The treatment of human LECs with 0 and 20% atmospheric O2 activated Nrf2/Keap1. The LECs shifted to 1% atmospheric O2 from 0, 4 or 20% for 24 h showed decreased levels of Keap1. By contrast, hLECs cultured in 1% atmospheric O2 for 24 h and then shifted to 0, 4 or 20% O2 exhibited a significant upregulation of Nrf2. These results suggest that oxidative stress proteins were not expressed in a 1% O2 environment. The O2 levels in the culture medium were equilibrated within 2 h in the cell culture plates. These results showed that an appropriate oxygen environment for the culture of LECs is ~1 % atmospheric O2. Either 0 or 20% of atmospheric O2 activated the UPR and the Nrf2/Keap1-mediated antioxidant system in LECs and chronic exposure to O2 fluctuation led to ROS production and cell death. This study revealed that O2 fluctuation-induced UPR/ER stress could be prevented by maintaining the cells in a 1% O2 environment.

Cataract research in India: A scientometric study of publications output, 2002-2011

Analyses the 1293 Indian publications in cataract research during 2002-2011, with a focus on contribution and citation impact of 15 most productive countries, India's overall contribution, its growth, citation impact, the share of international collaborative papers, identification of significant countries in India's international collaboration, different types of cataract research, analyses of research by sub-fields and different population age groups, productivity, and impact of leading Indian institutions and authors and pattern of communication of Indian output in most productive journals. The Scopus Citation Database has been used to retrieve the data for 10 years (2002-2011). Indian publications increased from 87 papers in 2002 to 195 papers in 2011, witnessing an annual average growth rate of 10.03%, registering an average citation impact per paper of 3.26 and international collaborative share of 21.58% during 2002-2011. Suggest that the government should encourage the decision makers and ophthalmologists and allied persons involved in ophthalmic services to make serious efforts in reducing the burden of cataract disease by increasing the R&D, strengthening of national and international collaboration and improve the existing training programs for ophthalmologic professionals.

The work and influence of the Raghudeep Eye Clinic, Ahmedabad, India

Interview by Tanya Stezhka, Commissioning EditorDr Abhay R Vasavada completed his FRCS in 1980 from the Royal College of Surgeons, England, and started Raghudeep Eye Clinic, as a cataract speciality clinic in 1984 in Ahmedabad, India. He has been instrumental in positioning cataract management as a subspeciality, and in raising the bar for management outcomes, be it the popularization of intraocular lens (IOLs) or establishing phacoemulsification as a standard of care, in the entire Asia-Pacific region. His expertise extends to managing the most complex and challenging cataracts in adults and children. He has made important contributions to the understanding and practise of cataract surgery like: emphasizing the role of balancing phaco fluidics (step-down technique); innovating a versatile chop technique (step-by-step chop in situ and lateral separation); defining paradigms for challenging cases like dense cataracts, small pupils and subluxated cataracts; devising the ‘inside-out delineation’ technique for posterior polar cataracts; recognizing the entity of ‘cortico-capsular adhesions’; and many more. He firmly believes that quality care should extend to all strata of society. He runs a center in a small town, Dholka, where the highest quality of eye care is provided to lesser privileged sections of society at nominal charges. Research is his passion right from his early days. He set up the Iladevi Cataract & IOL Research Center (ICIRC), a center providing basic research facility in 1991. Today, ICIRC is a Government of India recognized research laboratory dedicated to basic research and translational research pertaining to commonly prevalent eye conditions. He is a distinguished member of different ophthalmic bodies, including the International Council of Ophthalmology (ICO), American Academy of Ophthalmology (AAO), American Society of Cataract and Refractive Surgery (ASCRS), European Society of Cataract and Refractive Surgeons (ESCRS), Academia Ophthalmologica Internationalis (AOI), Asia Pacific Academy of Ophthalmology (APAO), Asia-Pacific Association of Cataract & Refractive Surgeons (APACRS) and others.His contribution to ophthalmology has been recognized worldwide. Some of the most prestigious awards he has received include the Binkhorst Medal lecture by the ASCRS.

Lens density tracking in mice by Scheimpflug imaging

Scheimpflug imaging has recently been established for in vivo imaging of the anterior eye segment and quantitative determination of lens transparency in the mouse. This enables more effective investigations of cataract formation with the mouse model, including longitudinal studies. In order to enable recognition of disease-associated irregularities, we performed Scheimpflug measurements with the common laboratory inbred lines C57BL/6J, C3HeB/FeJ, FVB/NCrl, BALB/cByJ, and 129/SvJ in a period between 2 and 12months of age. C57BL/6J mice showed lowest mean lens densities during the test period. Progressive cortical lens opacification was generally observed, with the earliest onset in C57BBL/6J, C3HeB/FeJ, and 129/SvJ, between 2 and 6months after birth. Moreover, lenses of these inbred lines developed nuclear opacities. Calculated mean lens density significantly increased between 6 and 12months of age in all inbred strains except 129/SvJ. Lens densities (and the corresponding standard deviations) of FVB/NCrl and 129/SvJ increased most likely because of differences in the genetic background. Albinism as confounder might be excluded since the albino Balb/cByJ mice are more similar to the C57BL/6J or C3Heb/FeJ mice. We further identified strain-specific anterior lens opacities (C57BL/6J) and cloudy corneal lesions (C57BL/6J, FVB/NCrl, and BALB/cByJ) at later stages. In conclusion, our results indicate that there are lifelong opacification processes in the mouse lens. The highest lens transparency and a dark coat color, which prevents interference from light reflections, make mice with the C57BL/6J background most suitable for cataract research by Scheimpflug imaging. We show that lens densitometry by Scheimpflug imaging in mouse eyes can resolve differences of less than 1%, making it possible to detect differences in cataract development in different mouse strains, even if they are small.

放射性白内障的研究进展

晶状体是人体内对辐射最为敏感的组织之一，少于2 Gy急性辐射剂量的低电离辐射和少于5 Gy的长期辐射能诱导白内障。尽管在这一领域已经进行了许多研究，放射性白内障形成的机制还没有完全明确。深入了解放射性白内障形成的机制及剂量阈值，将有助于理解放射性白内障的形成，在促进放射性白内障的研究及临床治疗中起到重要作用。 The lens of the eye is recognized as one of the most radiosensitive tissues in the human body, and it is known that cataracts can be induced by acute doses of less than 2 Gy of low-LET ionizing radiation and less than 5 Gy of pro- tracted radiation. Although much work has been carried out in this area, the exact mechanisms of radiation cataracto- genesis are still not fully understood. In-depth understanding of nuclear radiation cataract formation mechanism and dose threshold, will help to understand the whole process of radioactive nuclear cataract formation, and that will play an important role in promoting nuclear radiation cataract research and clinical treatment.

The progress of proteomics approaches in cataract research

Researches on lens proteomics are becoming prevalent in recent years. Characterized by their high resolution and efficiency, proteomics approaches provide reliable methodological support for lenses proteomic research, which demonstrates a new orientation for revealing the mechanism of cataractogenesis. This review outlines the separation, identification and some novel approaches of proteomic techniques applied in recent lenses proteomic research.

Cataract research using electronic health records

BackgroundThe eMERGE (electronic MEdical Records and Genomics) network, funded by the National Human Genome Research Institute, is a national consortium formed to develop, disseminate, and apply approaches to research that combine DNA biorepositories with electronic health record (EHR) systems for large-scale, high-throughput genetic research. Marshfield Clinic is one of five sites in the eMERGE network and primarily studied: 1) age-related cataract and 2) HDL-cholesterol levels. The purpose of this paper is to describe the approach to electronic evaluation of the epidemiology of cataract using the EHR for a large biobank and to assess previously identified epidemiologic risk factors in cases identified by electronic algorithms.MethodsElectronic algorithms were used to select individuals with cataracts in the Personalized Medicine Research Project database. These were analyzed for cataract prevalence, age at cataract, and previously identified risk factors.ResultsCataract diagnoses and surgeries, though not type of cataract, were successfully identified using electronic algorithms. Age specific prevalence of both cataract (22% compared to 17.2%) and cataract surgery (11% compared to 5.1%) were higher when compared to the Eye Diseases Prevalence Research Group. The risk factors of age, gender, diabetes, and steroid use were confirmed.ConclusionsUsing electronic health records can be a viable and efficient tool to identify cataracts for research. However, using retrospective data from this source can be confounded by historical limits on data availability, differences in the utilization of healthcare, and changes in exposures over time.

Mass spectrometry‐based proteomics approaches applied in cataract research

Cataract, the opacification of the eye lens, is the leading cause of blindness worldwide--it accounts for approximately 42% of all cases. The lens fibers have the highest protein content within the body, more than 35% of their wet weight. Given the eye lens pure composition of highly abundant structural proteins crystallins (up to 90%), it seems to be an ideal proteomic entity to study and might be also hypothesized to model the other protein conformational diseases. Crystallins are extremely long-lived, and there is virtually no protein turnover. This provides great opportunities for post-translational modifications (PTM) to occur and to predispose lens to the cataract formation. Despite recent progress in proteomics, the human lens proteome remains largely unknown. Mass spectrometry hold great promise to determine which crystallin modifications lead to a cataract. Quantitative analysis of PTMs at the peptide level with proteomics is a powerful bioanalytical tool for lens-tissue samples, and provides more comprehensive results. New mass spectrometry-based approaches that are being applied to lens research will be highlighted. Finally, the future directions of proteomics cataract research will be outlined.

Impact of iris pigment and pupil size in ultraviolet radiation cataract in rat

To investigate the effect of iris pigment and pupil size in ultraviolet radiation (UVR)-induced cataract. Brown-Norway rats (pigmented) and Fischer-344 rats (non-pigmented) were unilaterally exposed in vivo to 5 kJ/m(2) UVR. Each strain was split into two groups, each receiving either mydriatic (tropicamide) or miotic (pilocarpine) eye-drops. One week after exposure, the degree of ocular inflammation and damage in the anterior segment was determined. The lenses were extracted, photographed and the degree of forward light scattering (cataract) was quantified. The cataract types differed between the two strains. All Fischer rats developed macroscopically identifiable UVR cataract while only 41% of Brown-Norway rats did so. All groups except the miotic Brown-Norway developed significant light scattering. The Fischer rats developed 3-4-fold more lens light scattering than the Brown-Norway rats. The miotic Fischer group exhibited significantly more light scattering than the mydriatic Fischer group. There was no significant difference in light scattering between the two Brown-Norway groups. There was a correlation between ocular inflammation and degree of light scattering, with Brown-Norway rats exhibiting less inflammation and lens light scattering. Pigmented rats develop less UVR cataract and less ocular inflammation than non-pigmented rats. Pupil size plays a smaller role in UVR cataract development in pigmented rats than in non-pigmented. The role of UVR-induced ocular inflammation in cataract development is still ambiguous.

Genetic epidemiology in age‐related cataract research

Abstract Purpose Age‐related cataracts are the major cause of blindness worldwide. However, the contribution of genetics to their etiology is largely unknown. In contrast, the congenital and juvenile forms of cataracts are mainly caused by de‐novo or hereditary mutations leading to severe changes in the structure and/or function of the corresponding proteins – as it is obvious from the dominant mode of inheritance of most of the mutations. In addition to rare mutations, these cataract‐causing genes have also polymorphic sites in their regulatory and coding sequences (single nucleotide polymorphisms, SNPs); they might contribute to minor changes in the structure and/or function of the corresponding proteins. These alterations could be cataractogenic per se (in a mild form) or they might lead to an increased sensitivity of the proteins to environmental stress. Methods In a new population‐based study in Augsburg (Germany), which will be finished in summer 2008, ~3000 probands have been asked for cataracts; the answers are being validated and further specified by the treating ophthalmologists. Results 16 SNPs from known cataract causing genes (coding for crystallins, connexins and transcription factors) have been identified to be informative without violation of the Hardy‐Weinberg equilibrium. They will be tested with respect to their association with age‐related cataracts by logistic regression allowing for adjustment with respect to age, gender and other confounding effects. Conclusion The results will be presented and discussed.

Postnatal Biochemical Changes in Rat Lens: An Important Factor in Cataract Models

Purpose: Administration of several cataractogenic agents is effective during the first 21 days of rat lens development, a period of the highest sensitivity of the tissue. Thus, cataract formation and lens maturation affect the biochemical profile of rat lens simultaneously and might be difficult to evaluate separately. The purpose of this study was to use high-resolution magic angle spinning proton nuclear magnetic resonance (HR-MAS 1H NMR) to investigate exclusively the effect of maturation on the metabolic profile of rat lens. Methods: Albino Sprague-Dawley rats (n = 15) were divided into five groups of three animals and sacrificed at designated times (7, 14, 20, 30, and 60 days). The lenses were dissected, frozen, and thereafter analyzed with HR-MAS 1H NMR spectroscopy. Special grouping patterns among the tissue samples of different age and the relative percentage changes in particular metabolite concentrations were evaluated using appropriate statistical methods (principal components, one-way ANOVA). Results: Time-dependent alterations in the metabolic profile of the rat lens tissue were dominated by a significant increase in taurine, hypo-taurine, and myoinositol concentrations at the age of 30 days. Contents of the energy metabolites and amino acids were nearly constant between the ages of 14 and 30 days, showing a significant decrease in the 60-day-old rat lenses. Conclusions: HR-MAS 1H NMR spectroscopy showed its suitability to assess the natural alterations in the metabolic profile of maturing rat lens. The results can be used in future cataract research designed to evaluate the metabolic effect of different cataractogenic agents during this postnatal period.

External factors in the development of cataract

To provide an update on the risk factors for cataract development. Review of the literature. Age and heredity are the most important risk factors associated with the different types of cataract. While the hereditary component is self-explanatory, increasing age serves as a surrogate for a number of potential external risk factors, the effect of which is cumulative. Identification of the risk factors that have a causal effect on cataract development may provide means for cataract prevention. There are only a few risk factors that satisfy the criteria for causal effect: smoking, which results in the increased risk of nuclear cataract, excessive UV-B exposure and diabetes that increase the risk of cortical cataract, and steroidal treatment, diabetes and ionising radiation that lead to the formation of posterior subcapsular opacity. The effect of medications on cataract development requires further study, since the effect of the diseases should be distinguished from that of treatment. 'Stop Smoking' and 'UV-B protection' campaigns are gaining momentum as preventative measures, while the attempts to actively prevent cataract with antioxidants have not been successful. Cataract research has been facilitated lately by improvements of precision and standardisation in measuring lens opacities. However, measurement precision on its own cannot give us a solution to this problem. The major studies repeatedly measure the exposure to the traditional health hazards, while the missing parts in the equation are those risk factors that we do not know about and therefore do not measure. New approaches and new hypotheses are needed.

Lens regeneration in mice: implications in cataracts

Lens regeneration in adult mice is possible when the lens capsule is left behind after lentectomy. The lens is regenerated by the remaining adherent lens epithelial cells, which differentiate to form lens fibres within days, showing normal morphology and bow regions. Epithelial to mesenchymal cell transformation is also seen during the early stages. The mouse, therefore, can become an indispensable animal model for cataract research, surgery and therapy.