Home / Deep Research / Fuchs Endothelial Corneal Dystrophy

Fuchs Endothelial Corneal Dystrophy

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Fuchs Endothelial Corneal Dystrophy. Core disease mechanisms, molecular an...

2026-05-11
Asta MONDO:0005321 Model: Asta Scientific Corpus Retrieval 17 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Fuchs Endothelial Corneal Dystrophy. Core disease mechanisms, molecular an...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 17
  • Snippets retrieved: 20

Relevant Papers

[1] Genetic mutations and molecular mechanisms of Fuchs endothelial corneal dystrophy

  • Authors: Xue Liu, Tao Zheng, Chuchu Zhao, Yi Zhang, Hanruo Liu et al.
  • Year: 2021
  • Venue: Eye and Vision
  • URL: https://www.semanticscholar.org/paper/12e7cdcdc924d1fde2012ef77fd55d89c3d6957d
  • DOI: 10.1186/s40662-021-00246-2
  • PMID: 34130750
  • PMCID: 8204469
  • Citations: 25
  • Influential citations: 2
  • Summary: The mutations of COL8A2, TCF4 , TCF8 , SLC4A11 and AGBL1 genes in Fuchs endothelial corneal dystrophy are summarized and several potential treatments related to the pathogenesis of Fuchs vascular disease are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.837) > Background Fuchs endothelial corneal dystrophy is a hereditary disease and the most frequent cause of corneal transplantation in the worldwide. Its main clinical signs are an accelerated decrease in the number of endothelial cells, thickening of Descemet’s membrane and formation of guttae in the extracellular matrix. The cornea’s ability to maintain stromal dehydration is impaired, causing painful epithelial bullae and loss of vision at the point when the amount of corneal endothelial cells cannot be compensated. At present, apart from corneal transplantation, there is no other effective treatment that prevents blindness. Main text In this review, we first summarized the mutations of COL8A2 , TCF4 , TCF8 , SLC4A11 and AGBL1 genes in Fuchs endothelial corneal dystrophy. The molecular mechanisms associated with Fuchs endothelial corneal dystrophy, such as endoplasmic reticulum stress and unfolded protein response pathway, oxidative stress, mitochondrial dysregulation pathway, apoptosis pathway, mitophagy, epithelial-mesenchymal transition pathway, RNA toxicity and repeat-associated non-ATG translation, and other pathogenesis, were then explored. Finally, we discussed several potential treatments related to the pathogenesis of Fuchs endothelial corneal dystrophy, which may be the focus of future research. Conclusions The pathogenesis of Fuchs endothelial corneal dystrophy is very complicated. Currently, corneal transplantation is an important method in the treatment of Fuchs endothelial corneal dystrophy. It is necessary to continuously explore the pathogenesis of Fuchs endothelial corneal dystrophy and establish the scientific foundations for the development of next-generation corneal therapeutics.

[2] Fuchs endothelial corneal dystrophy: current perspectives

  • Authors: Gustavo Vedana, G. Villarreal, A. Jun
  • Year: 2016
  • Venue: Clinical Ophthalmology (Auckland, N.Z.)
  • URL: https://www.semanticscholar.org/paper/5e711677fe86955a62fc79446631a033649025dd
  • DOI: 10.2147/OPTH.S83467
  • PMID: 26937169
  • PMCID: 4762439
  • Citations: 120
  • Influential citations: 6
  • Summary: Advances that have been made in understanding FECD’s clinical features, pathophysiology, and genetics are highlighted and recent advances in endothelial keratoplasty are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.693) > Fuchs endothelial corneal dystrophy (FECD) is the most common corneal dystrophy and frequently results in vision loss. Hallmarks of the disease include loss of corneal endothelial cells and formation of excrescences of Descemet’s membrane. Later stages involve all layers of the cornea. Impairment of endothelial barrier and pump function and cell death from oxidative and unfolded protein stress contribute to disease progression. The genetic basis of FECD includes numerous genes and chromosomal loci, although alterations in the transcription factor 4 gene are associated with the majority of cases. Definitive treatment of FECD is corneal transplantation. In this paper, we highlight advances that have been made in understanding FECD’s clinical features, pathophysiology, and genetics. We also discuss recent advances in endothelial keratoplasty and potential future treatments.
  • Snippet 2 (score: 0.621) > Fuchs endothelial corneal dystrophy (FECD) was first described by Professor Ernst Fuchs as "Dystrophia epithelialis" more than 100 years ago, when he noticed a pattern of slowly progressive corneal clouding with greater involvement of the inferior cornea, reduced corneal sensation, and diurnal variation in symptoms affecting primarily the epithelium in elderly patients. 1 Six years later with the development of the slit lamp biomicroscope, Koeppe observed the classic finding of guttae in the corneal endothelium of patients with the corneal edema described by Fuchs. 2 Subsequent authors found different clinical signs associated with the dystrophy including progression of endothelial changes to corneal edema, 2 reduced corneal endothelial cell (CEC) density with abnormal size and shape, formation of a markedly thickened Descemet's membrane (DM) containing guttae excrescences, spindle-shaped bundles of wide-spaced collagen, and the hereditary nature of the disease. 2,3 During the past 100 years, studies of pathophysiology have increased our understanding of this disease, and improved treatments have been developed. The aim of this paper was to review relevant information about FECD and provide current perspectives on this disorder. endothelium Human corneal endothelium is in a postmitotic state and postnatal cell loss is permanent. In FECD, dying cells leave spaces that are filled through the expansion of adjacent cells resulting in loss of cellular hexagonal morphology (pleomorphism) and variation in cell size (polymegathism). Extracellular matrix excrescences (guttae) appear as round dark areas within the cellular monolayer on specular microscopy. 8,11,20 In early-onset FECD, endothelial cells were highly active in producing more COL8 protein than normal and displayed an abundant, unusual RER. In late-onset FECD, melanin was found intracellularly and extracellularly, together with expanded RER, dilated mitochondria, and epithelial markers. These findings suggest that endothelial cells undergo metaplasia becoming more similar to fibroblasts and epithelial cells in FECD

[3] Animal Models in Eye Research: Focus on Corneal Pathologies

  • Authors: Alexis Loiseau, Gabrielle Raîche-Marcoux, Cloé Maranda, Nicolas Bertrand, Élodie Boisselier
  • Year: 2023
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/57e3924f29f7e81714289adbb30fa31f98be3bc8
  • DOI: 10.3390/ijms242316661
  • PMID: 38068983
  • PMCID: 10706114
  • Citations: 45
  • Influential citations: 1
  • Summary: This review discusses current animal models associated with human corneal pathologies, their utility in understanding ocular disease mechanisms, and their role as translational models for patients.
  • Evidence snippets:
  • Snippet 1 (score: 0.687) > Vision loss is also the primary symptom in patients with endothelial corneal dystrophies due to fluid retention (swelling of the cornea), leading to corneal edema which results in progressive loss of corneal transparency [252,[254][255][256][257][258]. This type of corneal dystrophy accounts for approximately 60% of all types of corneal dystrophies [252]. The discovery of the genetic basis of corneal dystrophies is not complete, and the molecular mechanisms of the different mutations in the pathogenesis of each corneal dystrophy remain unclear. The development of gene therapy in the initial stages of corneal dystrophies is an important scientific challenge for the future. In contrast to retinal dystrophies, corneal dystrophies are more amenable to such therapy because of the anatomical accessibility of the cornea [254]. > Fuchs endothelial corneal dystrophy (FECD) is the most common corneal dystrophy, with a prevalence ranging from 3 to 11% depending on the age, ethnicity, and sex of the population [255][256][257][258][259]. This genetically heterogeneous disease is the most frequent cause of corneal transplantation worldwide. Two forms of FECD exist-the rare early-onset form and the more common late-onset form [252,255,257]. Although the primary cause of this disease is unknown [254,260], this bilateral disease of the corneal endothelium is characterized by accelerated loss of corneal endothelial cells and the formation of extracellular matrix excrescences in Descemet's membrane, called guttae [256][257][258][259]. Endothelial cell oxidative stress, apoptosis, loss of pump function, and deposition of abnormal extracellular matrix occur in the initial stages of the disease. These responses are manifested by endothelial cell loss, enlargement, and change in morphology associated with Descemet's membrane thickening and guttae formation, leading to corneal edema until vision is lost.

[4] Therapeutic Potential of Emricasan, a Pan-Caspase Inhibitor, in Reducing Cell Death and Extracellular Matrix Accumulation in Fuchs Endothelial Corneal Dystrophy

  • Authors: Sohya Fujimoto, Mako Endo, Shigehito Tonomura, Fuuga Tsuji, Hirotaka Haraguchi et al.
  • Year: 2025
  • Venue: Cells
  • URL: https://www.semanticscholar.org/paper/0b6bd849ac02058de9ae66c789e2582173e4689e
  • DOI: 10.3390/cells14070498
  • PMID: 40214452
  • PMCID: 11988121
  • Citations: 3
  • Summary: It is suggested that emricasan exerts dual protective effects by inhibiting caspase-7-mediated ECM accumulation and broadly suppressing apoptosis, highlighting its potential as a pharmacological therapy for FECD.
  • Evidence snippets:
  • Snippet 1 (score: 0.680) > Fuchs endothelial corneal dystrophy (FECD) is a progressive eye disease characterized by the formation of guttae, excrescences of Descemet membrane, and corneal endothelial cell degeneration [1][2][3]. The disease typically begins with the formation of central guttae, which, as they become more confluent, cause light scatter and consequent visual impairment [4,5]. As the disease progresses, corneal endothelial dysfunction advances until the remaining endothelial cells can no longer maintain corneal deturgescence, resulting in corneal edema and severe vision loss [1][2][3]. While corneal transplantation remains the standard treatment for FECD, several challenges persist, including a global donor cornea shortage (particularly outside the United States), immune rejection, and long-term graft failure due to continued endothelial cell loss [6][7][8][9][10]. These limitations underscore the urgent need for alternative therapeutic approaches, particularly pharmacological interventions. > Various molecular pathways contribute to FECD pathogenesis, with apoptotic cell death representing a central mechanism supported by substantial evidence [3]. Corneal endothelial cells (CECs) in FECD patients demonstrate enhanced vulnerability to apoptosis triggered by oxidative stress compared with endothelial cells from healthy controls [11,12]. This susceptibility stems from multiple factors, including accumulated oxidative damage to DNA (particularly affecting mitochondrial DNA) and compromised antioxidant defense systems [11]. Cell death in FECD is further promoted by chronic activation of the unfolded protein response pathway [13][14][15]. The disease progression is accelerated by dysfunctional mitochondria and defective mitophagy mechanisms [16]. Moreover, the characteristic guttae formations trigger apoptotic cascades in adjacent CECs, establishing a self-perpetuating cycle of cellular degeneration [17]. These insights into FECD pathogenesis, particularly the pivotal role of apoptosis in disease progression, suggest that targeting apoptotic pathways could offer a promising therapeutic approach for FECD.

[5] The Sociodemographic and Risk Factors for Fuchs’ Endothelial Dystrophy: A Nationwide, Matched Case–Control Study in Taiwan

  • Authors: Yuh-Shin Chang, Chung‐Han Ho, Jhi-Joung Wang, S. Tseng, Ren-Long Jan
  • Year: 2022
  • Venue: Journal of Personalized Medicine
  • URL: https://www.semanticscholar.org/paper/3aa8aeb16188d0d89b3d5083336df4ba1c705bb7
  • DOI: 10.3390/jpm12020305
  • PMID: 35207793
  • PMCID: 8877330
  • Citations: 2
  • Summary: It is found that more than half of the FED patients in Taiwan were aged ≥45 years old, there was an equal female-to-male ratio (1.06:1), and patients with a lower income and living in northern Taiwan had higher odds of developing FED.
  • Evidence snippets:
  • Snippet 1 (score: 0.670) > Fuchs' corneal endothelial dystrophy (FED), the most common form of corneal dystrophy, affects the endothelium, which is the innermost layer of the cornea. FED is characterized by endothelial cell density reduction with endothelium cell morphology alterations including variation in cell shape, known as cellular pleomorphism, and variation in the cell size, known as polymegathism [1]. FED usually presents in the fifth decade of life and progresses over the next two to three decades with continued endothelium cell loss and dysfunction. Some FED patients may be asymptomatic in the early stages of the disease, but patients may have glare or reduced visual acuity, severe pain due to the corneal edema progression to stromal thickness, increased bulla formation, or even long-standing corneal vascularization [2]. > FED is a multifactorial disorder caused by a complex combination of genetic, biochemistry, biology, and environmental factors. The pathophysiology of FED remains unknown, although several proposed mechanisms have been reported [1,[3][4][5]. Channelopathy, related to mutations in the genes of the ion channels in the corneal endothelium appears to be an important pathogenetic factor in the development of FED [3,4]. Elevation of oxidative stress and reactive oxygen species accumulation could lead to apoptosis of endothelial cells and is also regarded as one major cause of the development of FED [1,4]. The epithelialmesenchymal transition, in which fibroblastic or epithelial cell phenotypes transform from endothelial cells, could result in the secretion of extracellular matrix proteins leading to abnormal deposition, is thought to be involved in the pathogenesis of FED [1,4,5]. > The estimated incidence and prevalence of FED varies greatly worldwide, with a higher prevalence in Europe and the USA and lower rates in Asia, possibly because of different genetic or environmental factors and a difference in clinical definitions of FED [6,7]. Being older than 40 years of age is a major risk factor for FED development [4,5,8].

[6] Towards Clinical Trials in Fuchs Endothelial Corneal Dystrophy: Classification and Outcome Measures—The Bowman Club Lecture 2019

  • Authors: Sanjay V. Patel
  • Year: 2019
  • Venue: BMJ Open Ophthalmology
  • URL: https://www.semanticscholar.org/paper/fdd57258229919cdb109d3ca9a65407ef3533fb4
  • DOI: 10.1136/bmjophth-2019-000321
  • PMID: 31414054
  • PMCID: 6668606
  • Citations: 25
  • Summary: Standardising the approach for defining FECD and careful thought about the outcomes of intervention that are reported will help make the results of future trials for FECD applicable in clinical practice.
  • Evidence snippets:
  • Snippet 1 (score: 0.633) > The surgical treatment of Fuchs endothelial corneal dystrophy (FECD) has advanced dramatically over the last two decades. Penetrating keratoplasty has been superseded by various iterations of endothelial keratoplasty, and currently, surgical removal of host Descemet membrane without keratoplasty is being investigated. These surgical advances have been accompanied by significant improvement of our understanding of the underlying disease mechanisms, not least the discovery that FECD in western populations is predominantly an intronic trinucleotide repeat expansion disorder in the transcription factor 4 gene that results in RNA toxicity and mis-splicing. Understanding the disease mechanisms augurs well for developing targeted molecular medical therapies, which will require careful clinical investigation through trials to prove their efficacy and safety. As the field advances towards clinical trials, investigators should carefully define the disease state being treated and consider the options for outcome measures relevant to the type of intervention. FECD, and the outcomes of interventions to treat the disease, can be measured in terms of corneal morphology, corneal function and clinical impact. Standardising the approach for defining FECD and careful thought about the outcomes of intervention that are reported will help make the results of future trials for FECD applicable in clinical practice.
  • Snippet 2 (score: 0.633) > The surgical treatment of Fuchs endothelial corneal dystrophy (FECD) has advanced dramatically over the last two decades. Penetrating keratoplasty has been superseded by various iterations of endothelial keratoplasty, and currently, surgical removal of host Descemet membrane without keratoplasty is being investigated. These surgical advances have been accompanied by significant improvement of our understanding of the underlying disease mechanisms, not least the discovery that FECD in western populations is predominantly an intronic trinucleotide repeat expansion disorder in the transcription factor 4 gene that results in RNA toxicity and mis-splicing. Understanding the disease mechanisms augurs well for developing targeted molecular medical therapies, which will require careful clinical investigation through trials to prove their efficacy and safety. As the field advances towards clinical trials, investigators should carefully define the disease state being treated and consider the options for outcome measures relevant to the type of intervention. FECD, and the outcomes of interventions to treat the disease, can be measured in terms of corneal morphology, corneal function and clinical impact. Standardising the approach for defining FECD and careful thought about the outcomes of intervention that are reported will help make the results of future trials for FECD applicable in clinical practice.

[7] Characterisation of the role played by ELMO1, GPR141 and the intergenic polymorphism rs918980 in Fuchs' dystrophy in the Indian population

  • Authors: Susmita Sharma, S. K. Basak, Sujata Das, D. P. Alone
  • Year: 2025
  • Venue: FEBS Open Bio
  • URL: https://www.semanticscholar.org/paper/214fe9d2f1a4e46ec64aca4291e02f3b0d6d7f43
  • DOI: 10.1002/2211-5463.70006
  • PMID: 39967558
  • PMCID: 12051025
  • Citations: 1
  • Summary: The results suggest that ELMO1 and GPR141 might play a significant role in FECD progression, however, further studies are required to better characterize the possible role of rs918980 and its nearby region in the regulation of ELMO1 and GPR141.
  • Evidence snippets:
  • Snippet 1 (score: 0.629) > The innermost part of the human cornea, the corneal endothelium (CE), plays a vital role in vision and is present on the Descemet membrane [1]. CE consists of corneal endothelial cells (CECs), which are enriched with Na + -K + ATPase, aquaporin and other channel proteins that regulate the water and ions exchange between the corneal stroma and aqueous humor, keeping the avascular cornea in a hydrated condition and maintains corneal clarity [2,3]. Dysregulation of these proteins leads to water retention in the corneal stroma, resulting in thickened Descemet's membrane, increased extracellular matrix (ECM) protein deposition, CECs loss, guttae formation, painful epithelial bullae leading to Fuchs' endothelial corneal dystrophy (FECD) [4][5][6][7]. Cellular and molecular mechanisms such as endothelial pump dysfunction, endothelial-mesenchymal transition (EndoMT), RNA toxicity, oxidative stress, apoptosis, mitophagy and unfolded protein response pathway dysregulation contribute to the disease [8]. FECD, the most common type of primary corneal dystrophy, was Abbreviations CE, corneal endothelium; CEC, corneal endothelial cell; DSEK, Descemet stripping endothelial keratoplasty; ECM, extracellular matrix; EMT, epithelial-mesenchymal transition; EndoMT, endothelial-mesenchymal transition; FECD, Fuchs endothelial corneal dystrophy; IL, interleukin; LVPEI, LV Prasad Eye Institute; NFκB, nuclear factor kappa B; qRT-PCR, quantitative real-time PCR; SNP, single nucleotide polymorphism; TF, transcription factor; TGF, transforming growth factor; UVA, ultraviolet A. > first reported by Ernst Fuchs in 1910 and follows an autosomal dominant inheritance pattern in families.

[8] Update on the genetics of corneal endothelial dystrophies

  • Authors: C. Kannabiran, S. Chaurasia, Muralidhar Ramappa, V. Mootha
  • Year: 2022
  • Venue: Indian Journal of Ophthalmology
  • URL: https://www.semanticscholar.org/paper/3080a90259e7d8e711648196c9dbb44611bdc589
  • DOI: 10.4103/ijo.IJO_992_22
  • PMID: 35791103
  • PMCID: 9426112
  • Citations: 17
  • Summary: Knowledge of the genetics of corneal endothelial dystrophies has considerably advanced within the last decade and has contributed to better diagnosis of these dystrophic diseases as well as opened up the possibility of novel therapeutic approaches based on the molecular mechanisms involved.
  • Evidence snippets:
  • Snippet 1 (score: 0.626) > Corneal endothelial dystrophies are a heterogeneous group of diseases with different modes of inheritance and genetic basis for each dystrophy. The genes associated with these diseases encode transcription factors, structural components of the stroma and Descemet membrane, cell transport proteins, and others. Congenital hereditary endothelial dystrophy (CHED) is associated with mutations in two genes, OVOL2 and SLC4A11, for dominant and recessive forms of CHED, respectively. Mutations in three genes are known to cause posterior polymorphous corneal dystrophy (PPCD). They are OVOL2 (PPCD1), ZEB1 (PPCD3), and GRHL1 (PPCD4). The PPCD2 locus involving the collagen gene COL8A2 on chromosome 1 is disputed due to insufficient evidence. Mutations in the COL8A2 gene are associated with early-onset Fuchs' endothelial corneal dystrophy (FECD). Several genes have been associated with the more common, late-onset FECD. Alterations in each of these genes occur in a fraction of patients, and the most prevalent genetic alteration in FECD patients across the world is a triplet repeat expansion in the TCF4 gene. Knowledge of the genetics of corneal endothelial dystrophies has considerably advanced within the last decade and has contributed to better diagnosis of these dystrophies as well as opened up the possibility of novel therapeutic approaches based on the molecular mechanisms involved. The functions of genes identified to date provide insights into the pathogenic mechanisms involved in each disorder.
  • Snippet 2 (score: 0.622) > Many recent advances in the genetics of corneal endothelial dystrophies have brought to light pathways and mechanisms underlying the development of these diseases and pointed to correlations between genotype and phenotype. Despite a high degree of genetic heterogeneity, particularly for PPCD and FECD, the prevalence of mutations in the existing genes are rapidly being defined in patients from different regions. The application of genome sequencing may further facilitate the identification of new loci or novel types of pathogenic changes in existing genes in the near future and enhance our understanding of the underlying genetics of these diseases. A significant corollary of the new developments in the field lies in the possibility of developing suitable new therapies for these disorders based on their known genetic and molecular mechanisms. Proof of concept has already been obtained for using specific approaches to inhibit the triplet repeat expansionmediated disease pathways in FECD. Genetic screening may aid in establishing a genotype-phenotype correlation for patients. In a majority of cases, a meticulous slit-lamp examination and histological analysis wherever available help in determining the exact nature of the endothelial disease, although a diagnosis in patients with unusual manifestations can be supported by genetic testing. In familial forms of PPCD, knowing the mutation can aid in early screening and detection of affected but asymptomatic individuals. Developments in genetics have improved our knowledge of the corneal endothelial dystrophies and reduced the inaccuracies in their nomenclature. An accurate diagnosis of the specific type of endothelial dystrophy assists in planning the most appropriate management strategy and prognostication of the clinical condition. Furthermore, with the advent of alternatives such as pharmacotherapy and targeted molecular therapy in the management of endothelial dystrophies, a precise diagnosis of the clinical phenotype has become increasingly paramount.

[9] Oxidative Stress and Cellular Protein Accumulation Are Present in Keratoconus, Macular Corneal Dystrophy, and Fuchs Endothelial Corneal Dystrophy

  • Authors: Linda Vottonen, A. Koskela, S. Felszeghy, Adam Wylęgała, Katarzyna Kryszan et al.
  • Year: 2023
  • Venue: Journal of Clinical Medicine
  • URL: https://www.semanticscholar.org/paper/c903728f6001fc361af98b67b3b9288d27a17eb9
  • DOI: 10.3390/jcm12134332
  • PMID: 37445366
  • PMCID: 10342758
  • Citations: 13
  • Summary: Results suggest that oxidative stress has a role in KC, MCD, and FECD at the cellular level as a secondary outcome, and antioxidant- and autophagy-targeted therapies could be included as supporting care when treating KC or corneal dystrophies.
  • Evidence snippets:
  • Snippet 1 (score: 0.624) > The main function of the endothelium is to maintain a healthy stroma by regulating stromal hydration and nutrition as the cornea lacks its own blood supply [8]. The nutrients for the endothelium and stromal cells must be derived from the aqueous humor located at the more posterior side. > Due to its important role as a refractive interface, corneal diseases, such as corneal dystrophies and keratoconus, threaten normal vision and affect patients' quality of life. Corneal dystrophies can be classified as epithelial and subepithelial, epithelial-stromal, stromal, and endothelial dystrophies [9]. However, these dystrophies are not restricted to a certain layer and can also influence acellular layers [4]. Corneal dystrophies are often inherited and noninflammatory conditions without systemic manifestations. Gradual progression is also a common nominator of corneal dystrophies. Despite the clear link between inheritance and disease prevalence, little is known about the pathological and molecular mechanisms involved in disease onset and progression. > Oxidative stress has been linked to keratoconus (KC), macular corneal dystrophy (MCD), and Fuchs endothelial corneal dystrophy (FECD) [10,11]. Other known corneal conditions to which oxidative stress is associated are pterygium, trauma, and chemical injury [12]. KC is a corneal disease affecting the epithelium, Bowman's layer, and stroma. It usually begins in puberty and is progressive until 30-40 years of age [13]. KC is the most common primary ectasia, which results in irregular astigmatism, myopia, and reduced visual acuity [14]. MCD is a stromal dystrophy in which the deposition of abnormal proteoglycans leads to loss of corneal transparency and decreased vision [15]. The disease usually begins between 10 and 30 years of age and is recognized throughout the world. The prevalence seems to be higher in communities where consanguinity is common.

[10] Mitophagy: An Emerging Target in Ocular Pathology

  • Authors: Jessica M. Skeie, D. Nishimura, Cheryl L. Wang, Gregory A. Schmidt, B. T. Aldrich et al.
  • Year: 2021
  • Venue: Investigative Ophthalmology & Visual Science
  • URL: https://www.semanticscholar.org/paper/0fce0ac8cdf8590910e18cd3f74c86e96461e919
  • DOI: 10.1167/iovs.62.3.22
  • PMID: 33724294
  • PMCID: 7980050
  • Citations: 47
  • Summary: It is imperative that mitophagy be investigated as a targetable mechanism in developing therapies for ocular diseases characterized by oxidative stress and mitochondrial dysfunction, as this review indicates.
  • Evidence snippets:
  • Snippet 1 (score: 0.614) > anterior chamber, 79 have high rates of mitochondrial activity as they utilize active ion pumping mechanisms to counteract the passive leak of aqueous humor into the stroma, and do not proliferate in response to injury. With the emergence of single-layer endothelial cell transplant techniques (Descemet membrane endothelial keratoplasty and Descemet stripping automated endothelial keratoplasty [DSAEK]), it has become imperative to understand these cells in more detail in order to maximize the success of surgical outcomes. Two common diseases that feature impaired CEC function, Fuchs endothelial corneal dystrophy (FECD) and diabetes mellitus, demonstrate the effects of altered mitophagy on disease progression, as discussed below. Fuchs Endothelial Corneal Dystrophy. FECD, the most prevalent indication for endothelial keratoplasty in the United States, 80 manifests as a result of genetic mutations (spontaneous and familial), as well as non-heritable risk factors including gender (female predominance) and smoking. The clinical hallmarks of FECD include cell death and extracellular matrix deposition, resulting in corneal edema and characteristic excrescences observable on the posterior cornea (guttae). 81 Cellular and ultracellular characteristics of FECD include channel protein dysfunction, mitochondrial dysfunction, ROS accumulation, ER stress, DNA alterations, unfolded protein response, and endothelial cell apoptosis/dropout. 81,82 Although FECD is a complex disease with several different primary mechanisms involved, secondary mitochondrial dysfunction and mitophagy play a central role in the decline of endothelial cell viability during the progression of this disease. > Halilovic et al. 83 showed that corneas from FECD patients have increased mtDNA damage, and expanded ex vivo FECD cells have decreased ATP production as a result of oxidative stress. These findings indicate that reduced mitochondrial respiratory capacity and reduced mitochondrial protein expression are central features of the FECD cellular disease phenotype. Importantly, ATP production deficits were rescued with the antioxidant N-acetylcysteine (NAC), indicating the importance of maintaining proper redox balance in CEC function. Furthermore, Ben

[11] Looking to the Future of Viral Vectors in Ocular Gene Therapy: Clinical Review

  • Authors: Chulpan B Kharisova, K. Kitaeva, V. Solovyeva, A. A. Sufianov, G. Z. Sufianova et al.
  • Year: 2025
  • Venue: Biomedicines
  • URL: https://www.semanticscholar.org/paper/9b18df124d45c5161f6ab2880a2a419186682de7
  • DOI: 10.3390/biomedicines13020365
  • PMID: 40002778
  • PMCID: 11852528
  • Citations: 14
  • Influential citations: 2
  • Summary: A review examines the concept of gene therapy and its application in the field of ocular pathologies, emphasizing the most recent scientific advances and their potential impacts on visual function status.
  • Evidence snippets:
  • Snippet 1 (score: 0.613) > Corneal dystrophies are a heterogeneous group of inherited diseases of the cornea accompanied by corneal damage. This pathology is classified depending on the affected corneal layer: epithelial and subepithelial dystrophies, Bowman's membrane dystrophies, and endothelial dystrophies. Each of these conditions exhibits a unique set of clinical features, variable patterns of inheritance, a distinct age of onset, and varying rates of progression. Corneal dystrophies can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner [106]. Various corneal dystrophies are caused by mutations in the CHST6 and KRT genes, KRT3 and KRT12, PIP5K3, SLC4A11, TACSTD2, TGFBI, and UBIAD1 [107]. Mutations in three genes are known to cause posterior polymorphic corneal dystrophy: OVOL2, ZEB1, and GRHL [108]. Some of the most common diseases of this group are Fuchs' corneal endothelial dystrophy (FECD) and keratoconus, which will be described in this section.

[12] Exosomes and autophagy in ocular surface and retinal diseases: new insights into pathophysiology and treatment

  • Authors: Shisi Ma, Xiao Liu, Jiayang Yin, Lili Hao, Yuyao Diao et al.
  • Year: 2022
  • Venue: Stem Cell Research & Therapy
  • URL: https://www.semanticscholar.org/paper/0b2f71753b36ab64128e70e6ec7e092664090601
  • DOI: 10.1186/s13287-022-02854-8
  • PMID: 35505403
  • PMCID: 9066793
  • Citations: 14
  • Summary: The relationship between exosomes and autophagy is mostly focused on fundus diseases, while a deeper understanding of them will provide new directions for the pathological mechanism, diagnosis, and treatment of ocular surface and retinal diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.612) > Corneal dystrophy (CD) with the abnormal deposition of substances in the cornea, is sub-classified by the anatomic location affected: epithelial/subepithelial, epithelial-stromal, stromal, and endothelial dystrophies [77]. Corneal endothelial cells are attached to the descemet membrane, results in vision impairment and corneal edema when damage or loss [78,79]. Previous study indicates that mesenchymal stem cell-derived extracellular vesicles down-regulate the endoplasmic reticulum stressrelated genes, up-regulate the Akt pathway to inhibit the levels of apoptosis related caspase-3 activation in human corneal endothelial cells in vitro model, suggesting a potential therapeutic effect on corneal endothelial dystrophy [80]. > Fuchs endothelial corneal dystrophy (FECD) is the most common corneal endothelial dystrophy, which is a genetically complex, heterogenous, age-related degenerative disease of corneal endothelial cells with a higher incidence in females. The activation of PINK1-Parkinmediated mitophagy could degrade mitochondrial quality control proteins in FECD [81]. Lattice corneal dystrophy (LCD) is a degenerative disorder that causes loss of corneal transparency and eventually leads to loss of vision, and the reversion of the defective autophagic process in macrophages might be a therapeutic strategy for patients. The impairment of autophagic degradation of mutant transforming growth factor-β-induced protein (Mu TGFBIp) as a result of incomplete autophagy flux in macrophages, which prevented the further phagocytic activation and lead to LCD [82]. Thiel-Behnke corneal dystrophy (TBCD) caused by mutations of TGFB is an epithelial-stromal dystrophy and will be treated by the activation of autophagic flux and the amelioration of lysosomal function [83].

[13] Methylation in cornea and corneal diseases: a systematic review

  • Authors: Yutong Xia, Kuangqi Chen, Qianjie Yang, Zhitong Chen, Le Jin et al.
  • Year: 2024
  • Venue: Cell Death Discovery
  • URL: https://www.semanticscholar.org/paper/b662dc58df9e68e05829396ae03dbc2a4cb98ed3
  • DOI: 10.1038/s41420-024-01935-2
  • PMID: 38589350
  • PMCID: 11002037
  • Citations: 11
  • Summary: The major alterations of methylation and demethylation at the DNA, RNA, and protein levels in corneal diseases and how these dynamics contribute to the pathogenesis of corneal diseases are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.607) > Corneal dystrophies are rare genetic disorders that impact both eyes. They occur due to the accumulation of specific substances produced in various layers of the cornea. There are different classifications of corneal dystrophies depending on anatomical structure, clinical manifestations, and inherence patterns [183,184]. Currently, methylation studies on corneal dystrophies are mainly conducted in Fuchs endothelial cell dystrophy (FECD), with a few in Granular corneal dystrophy type 2 (GCD2) [185][186][187]. > The most prevalent corneal endothelial dystrophy, FECD, is a significant indicator and the leading cause of corneal transplant surgeries among patients worldwide [188,189]. FECD is a highly prevalent, progressively bilateral disease [190]. Generally, the gradual and persistent loss and dysfunction of endothelial cells in both structures and function eventually result in corneal edema [142,191]. The corneal endothelial cells (CEnCs) are derived from the neural crest and are in a specialized extracellular mesenchyme. Many diseases that impact CEnCs can compromise corneal function and visual acuity. Therefore, it is crucial to maintain a specific physiological range of stromal hydration for clear vision [192]. FECD is linked to several spontaneous and inherited mutations, characterized by abnormal accumulation of extracellular mesenchyme, but the underlying molecular pathogenesis of it is unknown [187,193]. DNA methylation has recently been suggested to affect corneal endothelial metabolism, cytoskeletal structure, and ion transport [186]. Some investigators have speculated that DNA methylation patterns may contribute to corneal edema and the resulting loss of corneal transparency in FECD [12]. Besides, miRNA gene promoters are often affected by abnormal DNA methylation in FECD. miRNAs, which are tiny noncoding RNAs that have undergone extensive evolutionary conservation, regulate not only fundamental biological processes including development, stress, and metabolism but also the entire course of disease development [194,195]. The extracellular matrix (ECM) inducible genes snail and ZEB1 are highly expressed in FECD [119].

[14] The application of high-throughput sequencing technology in corneal diseases

  • Authors: Jing Zhao, Yu xi He, Meiliang Wu, Rui Wang
  • Year: 2024
  • Venue: International Ophthalmology
  • URL: https://www.semanticscholar.org/paper/9b03ca82ba8d22d7ae326bab2ab4d8956aa5b636
  • DOI: 10.1007/s10792-024-03049-1
  • PMID: 38340174
  • PMCID: 10858842
  • Citations: 2
  • Summary: The application progress of high-throughput sequencing technology in corneal diseases is introduced, which will help to understand the application of this technology in various corneal diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.606) > Corneal dystrophy is a progressive keratopathy that is primarily inherited within families. Abnormal genes regulate cells in normal corneal tissue, leading to gradual damage to the structure and function of the cornea. According to the location of the disease, it can be divided into the following three categories: (1) Anterior corneal dystrophy, involving the epithelium and Bowman membrane; (2) Stromal corneal dystrophy involving the stroma or central layer of the cornea; (3) Posterior corneal dystrophy involving Descemet membranes and endodermis. Corneal dystrophy is typically inherited in an autosomal pattern. Due to the specific pathogenic gene and chromosome localization of different subtypes, patients with the same gene mutation may exhibit varying clinical manifestations (Table 2). > At present, the clinical diagnosis of corneal dystrophy needs to be combined with a detailed eye examination, including the examination of the anterior chamber Angle, lens and posterior segment of the eye. Imaging techniques, such as photography, red reflection photographs, optical coherence tomography, mirror microscopy, and living corneal confocal microscopy can be used to provide a comprehensive view of the condition [26]. > However, a definitive diagnosis requires genetic testing. High-throughput sequencing was performed on genes associated with corneal dystrophy to screen out mutant genes, supplemented by molecular karyotype analysis in order to clarify the typing and genetic pattern, and thus achieve precise treatment. Riazuddin et al. [27] used high-throughput sequencing technology to carry out whole gene scanning and found that missense mutation C.2969 g > C in AGBL1. This mutation affects the encoding of AGBL1, a cytoplasmic glutamate decarboxylase, and reduces its interaction with TCF4. The authors suggest that TCF4 may be an enzymatic target of AGBL1 and this interaction could potentially explain development of Fuchs endothelial corneal dystrophy (FECD). Zhang et al. [28] performed TRIa-based whole exome sequencing on a patient with congenital hereditary endothelial dystrophy (CHED) and their parents.

[15] Emerging Innovations in the Treatment of Fuchs Endothelial Corneal Dystrophy: A Narrative Review

  • Authors: Magdalena Niestrata, James Jackson, Shehnaz Bazeer, M. Gong, Zahra Ashena
  • Year: 2025
  • Venue: Medical Sciences
  • URL: https://www.semanticscholar.org/paper/95d19820ef24391851b19ca62c2e8cab4a4ae2d4
  • DOI: 10.3390/medsci13040238
  • PMID: 41283239
  • PMCID: 12642020
  • Summary: This narrative review summarises current and emerging therapeutic strategies for FECD and outlines future directions that are likely to combine advanced surgical techniques with cell-based and biomaterial solutions to deliver accessible, long-term restoration of vision for patients with FECD.
  • Evidence snippets:
  • Snippet 1 (score: 0.600) > Fuchs endothelial corneal dystrophy (FECD) is a degenerative eye disorder characterised by the progressive loss of endothelial cells in the cornea, which are crucial for maintaining corneal clarity by regulating fluid balance. As these cells deteriorate, fluid accumulates within the cornea, resulting in corneal oedema, clouding, and subsequent vision loss. This condition, although genetic, often manifests later in life making it more common in older adults. > Contemporary global meta-analysis estimates that approximately 7.33% of adults over 30 years of age are affected by Fuchs' endothelial corneal dystrophy, with prevalence projected to rise from around 300 million in 2020 to 415 million by 2050 [1]. > Recent research has shed more light on FECD's complex pathophysiology. Notably, the common late-onset form of FECD is associated with a non-coding trinucleotide repeat expansion in the TCF4 gene, leading to toxic RNA aggregates and oxidative stress in endothelial cells [2]. This results in the hallmark formation of guttae (focal collagen excrescences on Descemet's membrane) and accelerates endothelial cell loss. Early-onset familial FECD, in contrast, often stems from missense mutations (e.g., in COL8A2), causing more aggressive endothelial failure [2]. Ultimately, as endothelial pump function declines, corneal hydration increases and oedema worsens, triggering the visual decline observed in FECD. Understanding these disease mechanisms underscores the development of effective treatment modalities. > With the global population ageing, the incidence of FECD is expected to rise, leading to an increase in cases of corneal decompensation, particularly after common procedures like cataract surgery. This decompensation occurs when the already compromised endothelial cells are unable to recover from the stress of surgery, exacerbating the condition and accelerating the need for intervention. > Currently, the gold standard treatment for FECD is Descemet membrane endothelial keratoplasty (DMEK). This advanced surgical procedure involves replacing the diseased endothelial layer with healthy donor tissue.

[16] A family of fuchs endothelial corneal dystrophy and anterior polar cataract with an analysis of whole exome sequencing

  • Authors: Xue Jiang, Xin Jin, N. Zhang, Hong Zhang
  • Year: 2020
  • Venue: Ophthalmic Genetics
  • URL: https://www.semanticscholar.org/paper/81553fa52037540bf35082f7b1423c6ee23a9135
  • DOI: 10.1080/13816810.2020.1759109
  • PMID: 32367751
  • Citations: 2
  • Influential citations: 1
  • Summary: A family of FECD with APC is introduced, with no known causative gene found by WES, inferring that there may be a novel gene-locus in the non-coding regions of genome, which needs further study by WGS.
  • Evidence snippets:
  • Snippet 1 (score: 0.597) > Fuchs endothelial corneal dystrophy (FECD, OMIM:136800) is the most common form of corneal dystrophy, first documented by Ernst Fuchs in 1910 (1). FECD is a bilateral, slowly progressive corneal disease. It is characterized by deterioration of endothelial cells and development of guttae excrescences of Descemet's membrane (1)(2)(3)(4), which may eventually lead to corneal edema and reduced vision (4,5). The pathophysiology of FECD involves several proposed mechanisms involving channelopathies, oxidative stress, apoptosis, and the epithelial-mesenchymal transition. The underlying pathophysiology remains unknown (6,7).The prevalence of FECD in people over 50 years old is 4%-9%, varing by regions (5,6,8). In contrast to Caucasians with much higher FECD prevalence, fewer cases of FECD occur in the Asian population (7). > Age and gender are important factors influencing the development of FECD. People over 40 and female have a higher risk, with a female-to-male ratio of 2.5-3:1 (1,5,6). FECD displays in an autosomal dominant inheritance with incomplete penetrance, about 50% of the patients have a positive family history (6,9). Clinically, FECD can be divided into early-onset FECD and late-onset FECD. Early-onset FECD, which began in the first decade of life, shows similar progress to classic phenotypes. The initial clinical manifestation of late-onset form of FECD (corneal guttae) usually occurs in the fourth decade of life (1,6,10). Usually, patients do not need intervention until the sixth or seventh decades (1,6). > FECD is genetically complex and several genetic variations are known to be related to it (5). Mutations in COL8A2 (OMIM: 120252) is associated with the rare early-onset FECD.

[17] Pathological molecular mechanism of symptomatic late-onset Fuchs endothelial corneal dystrophy by bioinformatic analysis

  • Authors: Zekai Cui, Qiaolang Zeng, Yonglong Guo, Shiwei Liu, Peiyuan Wang et al.
  • Year: 2018
  • Venue: PLoS ONE
  • URL: https://www.semanticscholar.org/paper/701c4f26f1761f8156b9e9d7f991a1310f152a7d
  • DOI: 10.1371/journal.pone.0197750
  • PMID: 29787599
  • PMCID: 5963778
  • Citations: 25
  • Influential citations: 1
  • Summary: It is revealed that down-regulated IL-6, enhanced NF-κB activity and a suite of orchestrated chemokine responses induce fibrocyte differentiation from monocyte to dendritic cell maturation, and PI3K plays a key role in the molecular mechanism of symptomatic late-onset FECD.
  • Evidence snippets:
  • Snippet 1 (score: 0.592) > Fuchs endothelial corneal dystrophy (FECD) is a degenerative disease characterized by corneal endothelial decompensation. FECD causes corneal stromal and epithelial edema and progressively develops into bullous keratopathy, which can eventually lead to blindness. However, the exact pathogenesis is unknown. In this study, we performed an in-depth bioinformatic analysis of the dataset GSE74123 to determine the differentially expressed genes (DEGs) of symptomatic late-onset FECD compared with a normal control. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the pathological molecular mechanism of FECD. We found that cell senescence, reactive oxygen species (ROS), the extracellular matrix (ECM), epithelial-mesenchymal transition (EMT) and immune response-related genes play an important role in the pathological development of symptomatic late-onset FECD. In addition, we revealed that down-regulated IL-6, enhanced NF-κB activity and a suite of orchestrated chemokine responses induce fibrocyte differentiation from monocyte to dendritic cell maturation. PI3K plays a key role in the molecular mechanism of symptomatic late-onset FECD. This study enhances our understanding of the molecular mechanism of FECD pathogenesis and will improve the diagnostics and therapy of FECD patients in the future.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.