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Annual Review of Vision Science Sep 2019Cataract, the clinical correlate of opacity or light scattering in the eye lens, is usually caused by the presence of high-molecular-weight (HMW) protein aggregates or... (Review)
Review
Cataract, the clinical correlate of opacity or light scattering in the eye lens, is usually caused by the presence of high-molecular-weight (HMW) protein aggregates or disruption of the lens microarchitecture. In general, genes involved in inherited cataracts reflect important processes and pathways in the lens including lens crystallins, connexins, growth factors, membrane proteins, intermediate filament proteins, and chaperones. Usually, mutations causing severe damage to proteins cause congenital cataracts, while milder variants increasing susceptibility to environmental insults are associated with age-related cataracts. These may have different pathogenic mechanisms: Congenital cataracts induce the unfolded protein response and apoptosis. By contrast, denatured crystallins in age-related cataracts are bound by α-crystallin and form light-scattering HMW aggregates. New therapeutic approaches to age-related cataracts use chemical chaperones to solubilize HMW aggregates, while attempts are being made to regenerate lenses using endogenous stem cells to treat congenital cataracts.
Topics: Apoptosis; Cataract; Crystallins; Eye Diseases, Hereditary; Humans; Stem Cell Transplantation
PubMed: 31525139
DOI: 10.1146/annurev-vision-091517-034346 -
Progress in Retinal and Eye Research May 2021The Zonule of Zinn, or ciliary zonule, is the elaborate system of extracellular fibers that centers the lens in the eye. In humans, the fibers transmit forces that... (Review)
Review
The Zonule of Zinn, or ciliary zonule, is the elaborate system of extracellular fibers that centers the lens in the eye. In humans, the fibers transmit forces that flatten the lens during the process of disaccommodation, thereby bringing distant objects into focus. Zonular fibers are composed almost entirely of 10-12 nm-wide microfibrils, of which polymerized fibrillin is the most abundant component. The thickest fibers have a fascicular organization, where hundreds or thousands of microfibrils are gathered into micrometer-wide bundles. Many such bundles are aggregated to form a fiber. Dozens of proteins comprise the zonule. Most are derived from cells of the non-pigmented ciliary epithelium in the pars plana region, although some are probably contributed by the lens and perhaps other tissues of the anterior segment. Zonular fibers are viscoelastic cables but their component microfibrils are rather stiff structures. Thus, the elastic properties of the fibers likely stem from lateral interactions between microfibrils. Rupture of zonular fibers and subsequent lens dislocation (ectopia lentis) can result from blunt force trauma or be a sequela of other eye diseases, notably exfoliation syndrome. Ectopia lentis is also a feature of syndromic conditions caused typically by mutations in microfibril-associated genes. The resulting ocular phenotypes raise the possibility that the zonule regulates lens size and shape, globe size, and even corneal topology, in addition to its well-recognized role in accommodation.
Topics: Ciliary Body; Ectopia Lentis; Fibrillins; Humans; Lens, Crystalline; Microfibrils
PubMed: 32980533
DOI: 10.1016/j.preteyeres.2020.100902 -
Indian Journal of Ophthalmology Jul 2022Microspherophakia is a rare developmental abnormality of the crystalline lens with a myriad of ocular and systemic associations. Glaucoma is a serious complication... (Review)
Review
Microspherophakia is a rare developmental abnormality of the crystalline lens with a myriad of ocular and systemic associations. Glaucoma is a serious complication associated with this disorder. Early identification of the disease, timely visual rehabilitation, and appropriate management of the lens and glaucoma can help us prevent blindness from this condition. Multidisciplinary care with lifelong follow-up is recommended, as this typically affects the younger population. Current treatment protocols for this condition are mainly based on case reports and retrospective studies with shorter follow-up. Due to the rarity of this disease, designing a large randomized controlled trial to identify the merits and demerits of each management strategy is challenging. With cataract, glaucoma, and vitreoretinal specialists, each having their preferred way of managing microspherophakic lenses, we decided to do a comprehensive review of the existing literature to devise an integrated approach toward effective management of these patients. This review will collate all evidence and provide a very practical decision-making tree for its management.
Topics: Corneal Diseases; Ectopia Lentis; Glaucoma; Humans; Iris; Randomized Controlled Trials as Topic; Retrospective Studies; Visual Acuity
PubMed: 35791105
DOI: 10.4103/ijo.IJO_2888_21 -
IEEE Journal of Translational... 2021Cataract, which is the clouding of the crystalline lens, is the most prevalent eye disease accounting for 51% of all eye diseases in the U.S. Cataract is a progressive...
OBJECTIVE
Cataract, which is the clouding of the crystalline lens, is the most prevalent eye disease accounting for 51% of all eye diseases in the U.S. Cataract is a progressive disease, and its early detection is critical for preventing blindness. In this paper, an efficient approach to identify cataract disease by adopting luminance features using a smartphone is proposed.
METHODS
Initially, eye images captured by a smartphone were cropped to extract the lens, and the images were preprocessed to remove irrelevant background and noise by utilizing median filter and watershed transformation. Then, a novel luminance transformation from pixel brightness algorithm was introduced to extract lens image features. The luminance and texture features of different types of cataract disease images could be obtained accurately in this stage. Finally, by adopting support vector machines (SVM) as the classification method, cataract eyes were identified.
RESULTS
From all the images that we fed into our system, our method could diagnose diseased eyes with 96.6% accuracy, 93.4% specificity, and 93.75% sensitivity.
CONCLUSION
The proposed method provides an affordable, rapid, easy-to-use, and versatile method for detecting cataracts by using smartphones without the use of bulky and expensive imaging devices. This methodcan be used for bedside telemedicine applications or in remote areas that have medical shortages. Previous smartphone-based cataract detection methods include texture feature analysis with 95 % accuracy, Gray Level Co-occurrence Matrix (GLCM) method with 89% accuracy, red reflex measurement method, and RGB color feature extraction method using cascade classifier with 90% accuracy. The accuracy of cataract detection in these studies is subject to changes in smartphone models and/or environmental conditions. However, our novel luminance-based method copes with different smartphone camera sensors and chroma variations, while operating independently from sensors' color characteristics and changes in distances and camera angle. Clinical and Translational Impact-This study is an early/pre-clinical research proposing a novel luminance-based method of detecting cataract using smartphones for remote/at-home monitoring and telemedicine application.
Topics: Algorithms; Cataract; Humans; Smartphone; Support Vector Machine; Telemedicine
PubMed: 34786216
DOI: 10.1109/JTEHM.2021.3074597 -
Turkish Journal of Ophthalmology Aug 2023Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular... (Review)
Review
Pseudoexfoliation syndrome (PES) is one of the most common causes of open-angle glaucoma, with a higher risk of vision loss, a higher maximum and mean intraocular pressure (IOP) at diagnosis, and a wider range of IOP fluctuation compared to primary open-angle glaucoma. Patients with this syndrome have a ten-fold higher risk of developing glaucoma than the normal population. A definite diagnosis can be made by the observation of pseudoexfoliation material (PEM) on the anterior lens surface, ciliary processes, zonules, and iris. PEM deposits on the zonules may explain the clinically observed zonular weakness and lens subluxation or dislocation. An increased incidence of cataract development is also associated with PES. There is growing evidence for systemic associations of PES with peripheral, cardiovascular, and cerebrovascular system diseases, Alzheimer's disease, hearing loss, and increased plasma homocysteine levels. Indications for surgery are markedly more common in patients with pseudoexfoliation glaucoma than primary open-angle glaucoma. The goal of this article is to review the latest perspectives on the clinical features, therapy, and systemic associations of this clinically and biologically challenging disease.
Topics: Humans; Cataract; Exfoliation Syndrome; Glaucoma; Glaucoma, Open-Angle; Lens Subluxation
PubMed: 37602651
DOI: 10.4274/tjo.galenos.2023.76300 -
Experimental Eye Research Feb 2009Integrins are the major cell surface receptors for proteins in the extracellular matrix. These receptors form major cell signaling centers that are bidirectional,... (Review)
Review
Integrins are the major cell surface receptors for proteins in the extracellular matrix. These receptors form major cell signaling centers that are bidirectional, communicating messages between the cell and its environment. They are a large receptor family, with members well-known to regulate cellular processes essential to both development and disease. In this review we examine the literature regarding integrins in the lens. Here we cover integrin function in lens cell differentiation, in the development of the lens and in protection of the lens epithelial cell phenotype. In addition, we analyze the role of integrins in the progression of lens fibrotic diseases, focusing particularly on integrin regulation of TGFbeta signaling pathways in posterior capsule opacification (PCO) and anterior subcapsular cataract (ASC).
Topics: Animals; Embryonic Development; Female; Fibrosis; Humans; Integrins; Lens Diseases; Lens, Crystalline; Pregnancy; Signal Transduction
PubMed: 18671967
DOI: 10.1016/j.exer.2008.06.020 -
Developmental Dynamics : An Official... May 2020Ocular lens clouding is termed as cataract, which depending on the onset, is classified as congenital or age-related. Developing new cataract treatments requires new...
BACKGROUND
Ocular lens clouding is termed as cataract, which depending on the onset, is classified as congenital or age-related. Developing new cataract treatments requires new models. Thus far, Xenopus embryos have not been evaluated as a system for studying cataract.
RESULTS
We characterized the developmental process of lens formation in Xenopus laevis tailbuds and tadpoles, and we disrupted the orthologues of three mammalian cataract-linked genes in F0 by CRISPR/Cas9. We assessed the consequences of gene inactivation by combining external examination with histochemical analyses and functional vision assays. Inactivating the key metazoan eye development transcription factor gene pax6 produces a strong eye phenotype including an absence of eye tissue. Inactivating the genes for gap-junction protein and a nuclease, gja8 and dnase2b, produces lens defects that share several features of human cataracts, including impaired vision acuity, nuclei retention in lens fiber cells, and actin fibers disorganization. We tested the potential improvement of the visual acuity of gja8 crispant tadpoles upon treatment with the molecular chaperone 4-phenylbutyrate.
CONCLUSION
Xenopus is a valuable model organism to understand the molecular pathology of congenital eye defects, including cataracts, and to screen molecules with a potential to prevent or reverse cataracts.
Topics: Animals; Cataract; Clustered Regularly Interspaced Short Palindromic Repeats; Humans; Lens, Crystalline; Xenopus laevis
PubMed: 31872467
DOI: 10.1002/dvdy.147 -
Experimental Eye Research Aug 2022Neuropathological hallmarks of Alzheimer's disease (AD) include pathogenic accumulation of amyloid-β (Aβ) peptides and age-dependent formation of amyloid plaques in...
Neuropathological hallmarks of Alzheimer's disease (AD) include pathogenic accumulation of amyloid-β (Aβ) peptides and age-dependent formation of amyloid plaques in the brain. AD-associated Aβ neuropathology begins decades before onset of cognitive symptoms and slowly progresses over the course of the disease. We previously reported discovery of Aβ deposition, β-amyloidopathy, and co-localizing supranuclear cataracts (SNC) in lenses from people with AD, but not other neurodegenerative disorders or normal aging. We confirmed AD-associated Aβ molecular pathology in the lens by immunohistopathology, amyloid histochemistry, immunoblot analysis, epitope mapping, immunogold electron microscopy, quantitative immunoassays, and tryptic digest mass spectrometry peptide sequencing. Ultrastructural analysis revealed that AD-associated Aβ deposits in AD lenses localize as electron-dense microaggregates in the cytoplasm of supranuclear (deep cortex) fiber cells. These Aβ microaggregates also contain αB-crystallin and scatter light, thus linking Aβ pathology and SNC phenotype expression in the lenses of people with AD. Subsequent research identified Aβ lens pathology as the molecular origin of the distinctive cataracts associated with Down syndrome (DS, trisomy 21), a chromosomal disorder invariantly associated with early-onset Aβ accumulation and Aβ amyloidopathy in the brain. Investigation of 1249 participants in the Framingham Eye Study found that AD-associated quantitative traits in brain and lens are co-heritable. Moreover, AD-associated lens traits preceded MRI brain traits and cognitive deficits by a decade or more and predicted future AD. A genome-wide association study of bivariate outcomes in the same subjects identified a new AD risk factor locus in the CTNND2 gene encoding δ-catenin, a protein that modulates Aβ production in brain and lens. Here we report identification of AD-related human Aβ (hAβ) lens pathology and age-dependent SNC phenotype expression in the Tg2576 transgenic mouse model of AD. Tg2576 mice express Swedish mutant human amyloid precursor protein (APP-Swe), accumulate hAβ peptides and amyloid pathology in the brain, and exhibit cognitive deficits that slowly progress with increasing age. We found that Tg2576 trangenic (Tg) mice, but not non-transgenic (Tg) control mice, also express human APP, accumulate hAβ peptides, and develop hAβ molecular and ultrastructural pathologies in the lens. Tg2576 Tg mice exhibit age-dependent Aβ supranuclear lens opacification that recapitulates lens pathology and SNC phenotype expression in human AD. In addition, we detected hAβ in conditioned medium from lens explant cultures prepared from Tg mice, but not Tg control mice, a finding consistent with constitutive hAβ generation in the lens. In vitro studies showed that hAβ promoted mouse lens protein aggregation detected by quasi-elastic light scattering (QLS) spectroscopy. These results support mechanistic (genotype-phenotype) linkage between Aβ pathology and AD-related phenotypes in lens and brain. Collectively, our findings identify Aβ pathology as the shared molecular etiology of two age-dependent AD-related cataracts associated with two human diseases (AD, DS) and homologous murine cataracts in the Tg2576 transgenic mouse model of AD. These results represent the first evidence of AD-related Aβ pathology outside the brain and point to lens Aβ as an optically-accessible AD biomarker for early detection and longitudinal monitoring of this devastating neurodegenerative disease.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Animals; Brain; Cataract; Disease Models, Animal; Genome-Wide Association Study; Humans; Mice; Mice, Transgenic; Neurodegenerative Diseases
PubMed: 35202705
DOI: 10.1016/j.exer.2022.108974 -
Philosophical Transactions of the Royal... Apr 2011Millions are rendered blind or exhibit visual impairment due to pathologies of the lens of the eye. Lens research therefore addresses the direct need to gain insights...
Millions are rendered blind or exhibit visual impairment due to pathologies of the lens of the eye. Lens research therefore addresses the direct need to gain insights into the cellular and molecular basis of disease, but, moreover, serves as a valuable experimental system to answer fundamental biological questions. This themed issue showcases the scientific knowledge of the processes involved in the development, structure, ultrastructure, physiology and pathology of the lens and how this information has the potential to significantly further knowledge in various fields of research. The issue is divided into three main areas. Firstly, the lens is discussed as a developmental model for embryonic induction, as an elegant system for studying the role of growth factors in development, and for analysis of the molecular control and cellular basis of cellular differentiation. The genetic basis of disorders of lens development, including paediatric cataract (lens opacity), are also discussed in this section. Secondly, adult lens structure and ultrastructure are covered, as well as the lens as a model for homeostasis and solute exchange. Finally, the papers in the latter part of the special issue review lens pathology, including the lens as a model for normal and pathological ageing, vitreoretinal influences on lens function and cataract and the lens as a model for fibrotic disease. Overall, the articles highlight the lens as a continuing, very important and attractive model system for biologists working in many different research areas.
Topics: Aging; Embryonic Induction; Homeostasis; Humans; Lens Diseases; Lens, Crystalline
PubMed: 21402579
DOI: 10.1098/rstb.2010.0377 -
Journal of Radiation Research Sep 2014In 2011, the International Commission on Radiological Protection issued a statement on tissue reactions (formerly termed non-stochastic or deterministic effects) to... (Review)
Review
In 2011, the International Commission on Radiological Protection issued a statement on tissue reactions (formerly termed non-stochastic or deterministic effects) to recommend lowering the threshold for cataracts and the occupational equivalent dose limit for the crystalline lens of the eye. Furthermore, this statement was the first to list circulatory disease (cardiovascular and cerebrovascular disease) as a health hazard of radiation exposure and to assign its threshold for the heart and brain. These changes have stimulated various discussions and may have impacts on some radiation workers, such as those in the medical sector. This paper considers emerging issues associated with cataracts and cardiovascular disease. For cataracts, topics dealt with herein include (i) the progressive nature, stochastic nature, target cells and trigger events of lens opacification, (ii) roles of lens protein denaturation, oxidative stress, calcium ions, tumor suppressors and DNA repair factors in cataractogenesis, (iii) dose rate effect, radiation weighting factor, and classification systems for cataracts, and (iv) estimation of the lens dose in clinical settings. Topics for cardiovascular disease include experimental animal models, relevant surrogate markers, latency period, target tissues, and roles of inflammation and cellular senescence. Future research needs are also discussed.
Topics: Animals; Cardiovascular Diseases; Cataract; Dose-Response Relationship, Radiation; Environmental Exposure; Humans; Prevalence; Radiation Dosage; Radiation Injuries; Radiation Protection; Risk Assessment; Risk Factors
PubMed: 24824673
DOI: 10.1093/jrr/rru036