Experimental eye research最新文献

{"title":"The influence of polyacrylamide gel substrate elasticity on primary cultures of rat retinal ganglion cells","authors":"Matthias Strake ,&nbsp;Charlotte V. Fischer-Wedi ,&nbsp;Mohammed H. Khattab ,&nbsp;Peer Lauermann ,&nbsp;Carina Wollnik ,&nbsp;Christina Stanischa ,&nbsp;Hans Hoerauf ,&nbsp;Florian Rehfeldt ,&nbsp;Christian van Oterendorp","doi":"10.1016/j.exer.2024.110116","DOIUrl":"10.1016/j.exer.2024.110116","url":null,"abstract":"<div><div>In vitro primary cell culture models of retinal ganglion cells (RGC) are widely used to study pathomechanisms of diseases such as glaucoma. The biomechanic interaction with the culture substrate is known to influence core cellular functions. RGC cultures, however, are usually grown on rigid plastic or glass substrates. We hypothesized that soft polyacrylamide gel substrates may alter survival and neurite outgrowth of primary cultured RGC.</div><div>Primary retinal cultures from postnatal (day 1–6) Wistar rats were grown on glass coverslips or polyacrylamide (PA) gel substrate with different Young's elastic moduli (0.75, 10 or 30 kPa). Substrates were coated with Poly-l-lysine and/or laminin. RGC were immunostained with anti-beta-III-tubulin. Total neurite length, growth cone morphology, RGC density, mitochondrial morphology and transport as well as pro-survival pathways (Erk1/2, Akt, CREB) were assessed.</div><div>PA gel substrates of E = 10 kPa significantly increased the total neurite length by factor 1.5 compared to glass (p = 0.02). The growth cone area was significantly larger by factor 5.3 on 30 kPa gels (p = 0.01). The presence of a substrate coating was more important for neurite outgrowth and RGC survival on PA gels (poly-l-lysine &gt; laminin) than on glass. Neither mitochondrial morphology and motility nor the activation of pro-survival pathways significantly differed between the four substrates.</div><div>PA gel substrates significantly enhanced RGC neurite outgrowth. The signaling cascades mediating this effect remain to be determined.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"249 ","pages":"Article 110116"},"PeriodicalIF":3.0,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142389211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Schlemm's canal-selective Tie2/TEK knockdown induces sustained ocular hypertension in adult mice","authors":"Joon Schwakopf ,&nbsp;Cesar O. Romero ,&nbsp;Navita N. Lopez ,&nbsp;J. Cameron Millar ,&nbsp;Monica L. Vetter ,&nbsp;Alejandra Bosco","doi":"10.1016/j.exer.2024.110114","DOIUrl":"10.1016/j.exer.2024.110114","url":null,"abstract":"<div><div>Deficient Angiopoietin-Tie2 signaling is linked to ocular hypertension in glaucoma. Receptor Tie2/TEK expression and signaling at Schlemm's canal (SC) is indispensable for canal integrity and homeostatic regulation of aqueous humor outflow (AHO) and intraocular pressure (IOP), as validated by conditional deletion of <em>Tie2</em>, its ligands (<em>Angpt1, Angpt2 and Angpt3/4</em>) or regulators (<em>Tie1 and PTPRB/VE-PTP</em>). However, these <em>Tie2/TEK</em> knockouts and conditional knockouts are global or endothelial, preventing separation of systemic and ocular vascular defects that impact retinal or renal integrity. To develop a more targeted model of ocular hypertension induced by selective knockdown of <em>Tie2/TEK</em> expressed in SC, we combined the use of viral vectors to target the canal, and two distinct gene-editing strategies to disrupt the <em>Tie2</em> gene. Adeno-associated virus (AAV2) is known to transduce rodent SC when delivered into the anterior chamber by intracameral injection. First, delivery of Cre recombinase via AAV2.Cre into <em>R26</em> ^{<em>tdTomato/+</em>} reporter mice confirmed preferential and stable transduction in SC endothelium. Next, to disrupt <em>Tie2</em> expression in SC, we injected AAV2.Cre into homozygous floxed <em>Tie2</em> (<em>Tie2</em>^{<em>FL/FL</em>}) mice. This led to attenuated Tie2 protein expression along the SC inner wall, decreased SC area and reduced trabecular meshwork (TM) cellularity. Functionally, IOP was significantly and steadily elevated, whereas AHO facility was reduced. In contrast, hemizygous <em>Tie2</em>^{<em>FL/+</em>} mice responded to AAV2.Cre with inconsistent and low IOP elevation, corroborating the dose-dependency of ocular hypertension on Tie2 expression/activation. In a second model using CRISPR/SaCas9 genome editing, wild-type C57BL/6 J mice injected with AAV2.saCas9-sgTie2 showed similar selective SC transduction and comparable IOP elevation in course and magnitude to that induced by AAV2.Cre in <em>Tie2</em>^{<em>FL/FL</em>} mice. Together, our findings, demonstrate that selective <em>Tie2</em> knockdown in SC is a targeted strategy that reliably induces chronic ocular hypertension and reproduces glaucomatous damage to the conventional outflow pathway, providing novel models of SC-Tie2 signaling loss valuable for preclinical studies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110114"},"PeriodicalIF":3.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the persistence of large choroidal hypertransmission defects using SS-OCT imaging","authors":"Sara Beqiri ,&nbsp;Gissel Herrera ,&nbsp;Jeremy Liu ,&nbsp;Mengxi Shen ,&nbsp;Alessandro Berni ,&nbsp;Omar S. El-Mulki ,&nbsp;Yuxuan Cheng ,&nbsp;Omer Trivizki ,&nbsp;James Kastner ,&nbsp;Robert C. O'Brien ,&nbsp;Giovanni Gregori ,&nbsp;Ruikang K. Wang ,&nbsp;Philip J. Rosenfeld","doi":"10.1016/j.exer.2024.110117","DOIUrl":"10.1016/j.exer.2024.110117","url":null,"abstract":"<div><div>In age-related macular degeneration (AMD), large choroidal hypertransmission defects (hyperTDs) are identified on <em>en face</em> optical coherence tomography (OCT) images as bright lesions measuring at least 250 μm in greatest linear dimension (GLD). These choroidal hyperTDs arise from focal attenuation or loss of the retinal pigment epithelium (RPE). We previously reported that once large hyperTDs formed, they were likely to persist compared with smaller lesions that were more likely to be transient. Due to their relative persistence, these large persistent choroidal hyperTDs are a point-of-no-return in the progression of intermediate AMD to the late stage of atrophic AMD. Moreover, the onset of these large choroidal hyperTDs can serve as a clinical trial endpoint when studying therapies that might slow disease progression from intermediate AMD to late atrophic AMD. To confirm the persistence of these large choroidal hyperTDs, we studied an independent dataset of AMD eyes enrolled in an ongoing prospective swept-source OCT (SS-OCT) natural history study to determine their overall persistence. We identified a total of 202 eyes with large choroidal hyperTDs containing 1725 hyperTDs followed for an average of 46.6 months. Of the 1725 large hyperTDs, we found that 1718 (99.6%) persisted while only 7 hyperTDs (0.4%) were non-persistent. Of the 7 non-persistent large hyperTDs in 6 eyes, their average GLD at baseline was 385 μm. Of the large hyperTDs ranging in size between 250 and 300 μm when first detected, only one was not persistent with a baseline GLD of 283 μm. In 6 of the non-persistent hyperTDs, the loss of a detectable large hyperTD was due to the accumulation of hyperreflective material along the retinal pigment epithelium (RPE) and in the retina over the area where the hyperTD was located. This hyperreflective material is thought to represent the migration and aggregation of RPE cells into this focal region where the choroidal hyperTD arose due to attenuated or lost RPE.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110117"},"PeriodicalIF":3.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurement of absolute abundance of crystallins in human and αA N101D transgenic mouse lenses using 15N-labeled crystallin standards","authors":"Kate A. Halverson-Kolkind ,&nbsp;Nicholas Caputo ,&nbsp;Kirsten J. Lampi ,&nbsp;Om Srivastava ,&nbsp;Larry L. David","doi":"10.1016/j.exer.2024.110115","DOIUrl":"10.1016/j.exer.2024.110115","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Stable isotope labeled standards of all major human lens crystallins were created to measure the abundance of lens endogenous crystallins from birth to adulthood. All major human crystallins (αA, αB, βA2, βA3/A1, βA4, βB1, βB2, βB3, γA, γB, γC, γD, γS) were cloned with N-terminal 6 x His tagged SUMO for ease of purification and the ability to generate natural N-termini by SUMO protease cleavage when producing crystallins for structure/function studies. They were then expressed in &lt;sup&gt;15&lt;/sup&gt;N-enriched media, quantified by mass spectrometry, and mixed in proportions found in young human lens to act as an artificial lens standard. The absolute quantification method was tested using soluble protein from 5-day, 23-day, 18-month, and 18-year-old human lenses spiked with the &lt;sup&gt;15&lt;/sup&gt;N artificial lens standard. Proteins were trypsinized, relative ratios of light and heavy labeled peptides determined using high-resolution precursor and data independent MS2 scans, and data analysis performed using Skyline software. Crystallin abundances were measured in both human donor lenses and in transgenic mouse αA N101D cataract lenses. Technical replicates of human crystallin abundance measurements were performed with average coefficients of variation of approximately 2% across all 13 crystallins. αA crystallin comprised 27% of the soluble protein of 5-day-old lens and decreased to 16% by 18-years of age. Over this time period αB increased from 6% to 9% and the αA/αB ratio decreased from 4.5/1 to 2/1. γS-crystallin also increased nearly 2-fold from 7% to 12%, becoming the 3rd most abundant protein in adult lens, while βB1 increased from 14% to 20%, becoming the most abundant crystallin of adult lens. Minor crystallins βA2, βB3, and γA comprised only about 1% each of the newborn lens soluble protein, and their abundance dropped precipitously by adulthood. While 9 of the SUMO tagged crystallins were useful for purification of crystallins for structural studies, γA, γB, γC, and γD were resistant to cleavage by SUMO protease. The abundance of WT and N101D human αA in transgenic mouse lenses was approximately 40-fold lower than endogenous mouse αA, but the deamidation mimic human αA N101D was less soluble than human WT αA. The high content of αA and the transient abundance of βA2, βB3, and γA in young lens suggest these crystallins play a role in early lens development and growth. βB1 becoming the most abundant crystallin may result from its role in promoting higher order β-crystallin oligomerization in mature lens. The full set of human crystallin expression vectors in the Addgene repository should be a useful resource for future crystallin studies. &lt;sup&gt;15&lt;/sup&gt;N labeling of these crystallins will be useful to accurately quantify crystallins in lens anatomic regions, as well as measure the composition of insoluble light scattering crystallin aggregates. The standards will also be useful to measure the abundance of crystallins expressed in transgenic a","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110115"},"PeriodicalIF":3.0,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diminished light sensitivities of ON alpha retinal ganglion cells observed in a mouse model of hyperglycemia","authors":"Qin Wang ,&nbsp;Chunghim So ,&nbsp;Chunting Qiu ,&nbsp;Ting Zhang ,&nbsp;Kangyi Yang ,&nbsp;Feng Pan","doi":"10.1016/j.exer.2024.110113","DOIUrl":"10.1016/j.exer.2024.110113","url":null,"abstract":"<div><div>This study aimed to investigate potential functional changes in retinal ganglion cells (RGCs) in a mouse model of hyperglycemia and explore possible therapeutic approaches. Hyperglycemia resembling type 1 diabetes mellitus (DM) was induced in C57BL/6 mice through intraperitoneal injection of streptozotocin (STZ). Blood glucose levels were confirmed to be elevated after 1 week and 4 weeks of injection. Mice with blood glucose levels above 350 mg/mL after 4 weeks of one-dose STZ injection were considered hyperglycemic. The light sensitivity of ON alpha (α) retinal ganglion cells (RGCs), not OFF αRGCs, was reduced in the hyperglycemic mouse model. The number of apoptotic cells, RGCs, and amacrine cells (ACs) remained unaffected at this stage. Similarly, the eletroretinogram (ERG) and optokinetic test results showed no significant differences. The application of picrotoxin (PTX) to block GABA receptors could increase the light sensitivity of ON αRGCs by 1 log unit in hyperglycemic mice. The results show that ON αRGCs may be more susceptible to microenvironmental changes caused by hyperglycemia than OFF αRGCs. This decline in light sensitivity may occur before cell apoptosis during the early stages of the hyperglycemic mouse model but has the potential to be reversed.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110113"},"PeriodicalIF":3.0,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of NF-κB on inflammatory and angiogenic processes in age-related macular degeneration","authors":"Waleed Hassan Almalki ,&nbsp;Salem Salman Almujri","doi":"10.1016/j.exer.2024.110111","DOIUrl":"10.1016/j.exer.2024.110111","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) is a prominent cause of vision loss, characterized by two different types, dry (atrophic) and wet (neovascular). Dry AMD is distinguished by the progressive deterioration of retinal cells, which ultimately causes a decline in vision. In contrast, wet AMD is defined by the abnormal development of blood vessels underneath the retina, leading to a sudden and severe vision impairment. The course of AMD is primarily driven by chronic inflammation and pathological angiogenesis, in which the NF-κB signaling pathway plays a crucial role. The activation of NF-κB results in the generation of pro-inflammatory cytokines, chemokines, and angiogenic factors like VEGF, which contribute to inflammation and the formation of new blood vessels in AMD. This review analyzes the intricate relationship between NF-κB signaling, inflammation, and angiogenesis in AMD and assesses the possibility of using NF-κB as a target for therapy. The evaluation involves a comprehensive examination of preclinical and clinical evidence that substantiates the effectiveness of NF-κB inhibitors in treating AMD by diminishing inflammation and pathological angiogenesis.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110111"},"PeriodicalIF":3.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct activation of M1 and M2 macrophages in the primary pterygium lymphangiogenesis","authors":"Soo Jin Lee ,&nbsp;Ahra Koh ,&nbsp;Seung Hyeun Lee ,&nbsp;Kyoung Woo Kim","doi":"10.1016/j.exer.2024.110108","DOIUrl":"10.1016/j.exer.2024.110108","url":null,"abstract":"<div><div>The precise role and innate immunological mechanisms underlying lymphangiogenesis in pterygium remain unclear. This study aimed to investigate the presence of M1 and M2 macrophages and their correlation with pro-lymphangiogenic activation and lymphatic endothelial expression in human pterygium stromal tissues. We analyzed human pterygium and subject-matched normal conjunctival tissues for the expression of these factors and conducted <em>in vitro</em> experiments to assess interactions between macrophages and pterygium fibroblasts. Myeloid and M1 macrophage markers were upregulated in pterygium. M1 macrophages were associated with the upregulation of pro-lymphangiogenic vascular endothelial growth factor C (<em>Vegfc</em>) in pterygium tissues and induced inflammatory signals in pterygium fibroblasts. In contrast, lymphatic vessel endothelial hyaluronan receptor 1 (<em>Lyve1</em>) expression was associated with M2 markers but not with M1 markers. Notably, the clinical severity of pterygium was inversely correlated with the expression of the M2 marker <em>Cd163</em>. These findings suggest that M1 and M2 macrophages play distinct roles in the pathogenesis of pterygium, with M1 macrophages enhancing lymphangiogenic stimulation and inflammatory responses, while M2 macrophages are associated with <em>Lyve1</em> expression and reduced severity of pterygium. Understanding these mechanisms may advance our current understanding of lymphatic biology in pterygium.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110108"},"PeriodicalIF":3.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the connection between HLA class I and class II genotypes and diabetic retinopathy: A comprehensive review of experimental evidence","authors":"Zahra Souri ,&nbsp;Hamid Ahmadieh","doi":"10.1016/j.exer.2024.110112","DOIUrl":"10.1016/j.exer.2024.110112","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is a microvascular complication associated with diabetes mellitus (DM). During the course of the disease, high blood glucose levels induce damage to the vasculature of the retina and promote neovascularization. Although numerous environmental risk factors have been associated with the emergence of DR, the role of genetics should not be underestimated. The human leukocyte antigen (HLA) plays a significant role in the regulation of the immune system. DR exhibits significant heterogeneity among patients, with differences in how the disease presents and progresses over time. The HLA gene, characterized by its extensive genetic variation, largely contributes to this diverse spectrum. Differences in HLA allele frequencies among healthy people, diabetic patients without retinopathy, and diabetic patients with different stages of retinopathy highlight the need for proper management of the disease. This comprehensive review outlines the current understanding of the relationship between HLA class I and class II variants and DR, shedding light on their potential significance as early onset indicators, prognostic indicators, and important risk factors for the development of this retinal condition.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110112"},"PeriodicalIF":3.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current insights on mitochondria-associated endoplasmic reticulum membranes (MAMs) and their significance in the pathophysiology of ocular disorders","authors":"Xin-Yu Zhang ,&nbsp;Cheng Han ,&nbsp;Yong Yao ,&nbsp;Ting-Ting Wei","doi":"10.1016/j.exer.2024.110110","DOIUrl":"10.1016/j.exer.2024.110110","url":null,"abstract":"<div><div>The intricate interaction network necessary for essential physiological functions underscores the interdependence among eukaryotic cells. Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs), specialized junctions between mitochondria and the ER, were recently discovered. These junctions participate in various cellular processes, including calcium level regulation, lipid metabolism, mitochondrial integrity maintenance, autophagy, and inflammatory responses via modulating the structure and molecular composition of various cellular components. Therefore, MAMs contribute to the pathophysiology of numerous ocular disorders, including Diabetic Retinopathy (DR), Age-related Macular Degeneration (AMD) and glaucoma. In addition to providing a concise overview of the architectural and functional aspects of MAMs, this review explores the key pathogenetic pathways involving MAMs in the development of several ocular disorders.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110110"},"PeriodicalIF":3.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trio-based whole-exome sequencing of 200 Chinese patients with keratoconus","authors":"Xingyong Li ,&nbsp;Yinghao Yao ,&nbsp;Shilai Xing ,&nbsp;Yi-Han Zheng ,&nbsp;Yang Zhou ,&nbsp;Xiaoguang Yu ,&nbsp;Jianzhong Su ,&nbsp;Shihao Chen ,&nbsp;Zi-Bing Jin","doi":"10.1016/j.exer.2024.110109","DOIUrl":"10.1016/j.exer.2024.110109","url":null,"abstract":"<div><div>Keratoconus (KC) is a complex corneal disorder with a well-recognized genetic component. In this study, we aimed to expand the genetic spectrum of 200 Chinese patients with keratoconus and their unaffected parents. Trio-based whole-exome sequencing was performed in 200 patients with sporadic keratoconus and their unaffected parents. The variants identified in candidate genes for keratoconus were analyzed using multiple bioinformatics tools. Finally, we identified 7 variants in 5 candidate genes for keratoconus in 5 patients. The c.T464C variant in the <em>IMPDH1</em> gene was defined as likely pathogenic according to the guidelines of the American College of Medical Genetics and Genomics, and the remaining variants in candidate genes (<em>TRANK1</em>, <em>SLC4A11</em>, <em>CERKL</em>, <em>IFT172</em>) were defined as uncertain significance. Our results expand the genetic spectrum in KC, highlight the genetic heterogeneity of this disease and provide important clues for future functional validation.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"248 ","pages":"Article 110109"},"PeriodicalIF":3.0,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}