Jingyong Li , Ya Dan , Wei Su , Mingjun Zhao , Zhiguo Chen , Zhuyang Zhao
{"title":"Immune-related biomarkers in the neuromyelitis optica spectrum disorder; pathogenesis and therapeutic approaches","authors":"Jingyong Li , Ya Dan , Wei Su , Mingjun Zhao , Zhiguo Chen , Zhuyang Zhao","doi":"10.1016/j.exer.2025.110395","DOIUrl":"10.1016/j.exer.2025.110395","url":null,"abstract":"<div><div>Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system that mostly affects the optic nerves and spinal cord. About eighty percent of patients have antibodies that are directed against the water channel aquaporin-4 (AQP4)-IgG, which is expressed on astrocytes. This protein was shown to be both a biomarker and a pathogenic cause of NMOSD. Researchers have discovered that antibodies against myelin oligodendrocyte glycoprotein (MOG) IgG can serve as a biomarker for a distinct condition known as MOG antibody-associated disease (MOGAD). This condition shares some similarities with AQP4-IgG-positive NMOSD, but it has distinct differences in terms of its underlying causes, clinical characteristics, response to treatment, and prognosis. Identifying AQP4 antibodies in the blood serum confirms the diagnosis of seropositive NMOSD. Nevertheless, it remains uncertain if there is a correlation between AQP4-IgG levels and disease activity, severity, responsiveness to medication, or long-term effects. Furthermore, there is still a need to establish and confirm biomarkers specifically for patients diagnosed with seronegative NMOSD. This study primarily examines the immunological aspects of NMOSD, which might have significant consequences for clinical practice. These implications include the possible use of new biomarkers to aid in the early and correct diagnosis of NMOSD, as well as the development of current treatment options to enhance the long-term prognosis of NMOSD patients.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110395"},"PeriodicalIF":3.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916689","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":"TCF4 expansion–associated loss of FN1 intron retention drives extracellular matrix accumulation in Fuchs endothelial corneal dystrophy","authors":"Soichiro Inagaki , Taichi Yuasa , Theofilos Tourtas , Ursula Schlötzer-Schrehardt , Friedrich Kruse , Noriko Koizumi , Naoki Okumura","doi":"10.1016/j.exer.2025.110398","DOIUrl":"10.1016/j.exer.2025.110398","url":null,"abstract":"<div><div>Fuchs endothelial corneal dystrophy (FECD), which is characterized by excessive extracellular matrix (ECM) accumulation and corneal endothelial cell degeneration, has trinucleotide repeat expansion in <em>TCF4</em> as a major genetic risk factor. While aberrant splicing has been implicated in FECD pathogenesis, the mechanistic link between splicing abnormalities and disease-specific features remains unclear. Here, we investigated the intron retention (IR) patterns in corneal endothelial cells from FECD patients with <em>TCF4</em> expansion. Initial RNA-Seq analysis using rMATS identified 486 upregulated and 89 downregulated IR events in expansion-positive FECD compared to controls. Subsequent analysis with the more stringent IRFinder algorithm revealed 10 upregulated IR events distributed across nine genes and, notably, 6 downregulated events exclusively localized within <em>FN1</em>, a major component of corneal guttae. While DEXSeq analysis showed reduced expression across <em>FN1</em> gene regions in FECD samples, subsequent qPCR validation in an independent cohort demonstrated significantly elevated <em>FN1</em> expression in both expansion-positive and expansion-negative FECD samples compared to controls. This paradoxical finding suggests that the loss of normal IR-mediated regulation may contribute to pathological <em>FN1</em> overexpression in FECD. Gene ontology analysis of IR-associated genes revealed enrichment in RNA splicing and ECM-related pathways, supporting a role for IR in disease pathogenesis. Our findings reveal an association between <em>TCF4</em> expansion and reduced <em>FN1</em> intron retention, which correlates with ECM accumulation, suggesting a potential link between RNA processing alterations and hallmark features of FECD. These results suggest that targeting IR-mediated regulation could represent a therapeutic strategy for preventing disease progression.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110398"},"PeriodicalIF":3.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859824","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}
Yong Lin , Tianyi Xu , Qiuruo Jiang, Jialu Chen, Hua Zhang, Peter Sol Reinach, Dongsheng Yan, Jia Qu, Shihao Chen
{"title":"Fluorometholone inhibits corneal epithelial proliferation, migration via targeting Rho GTPases: RhoA, Rac1, and Cdc42","authors":"Yong Lin , Tianyi Xu , Qiuruo Jiang, Jialu Chen, Hua Zhang, Peter Sol Reinach, Dongsheng Yan, Jia Qu, Shihao Chen","doi":"10.1016/j.exer.2025.110397","DOIUrl":"10.1016/j.exer.2025.110397","url":null,"abstract":"<div><div>Abnormal corneal epithelial hyperplasia is a common complication following refractive surgery. 0.1 % fluorometholone (FML) eye drops are commonly used for treatment. However, their efficacy varies among patients, potentially attributed to differences in the patient's microenvironment. The underlying reason remains incompletely understood. This study aimed to elucidate the molecular mechanisms of FML's action on corneal epithelial cells (CECs). The effects of FML on the cell viability, proliferation, cell cycle, and migration of human corneal epithelial cells (HCECs) were evaluated using MTS assay, EdU staining, flow cytometry, and scratch assay, respectively. Mouse corneal sections were immunofluorescently stained to assess cell proliferation. A corneal wound model, monitored by slit-lamp photography, was utilized to evaluate the impact of FML on wound healing. Gene expression alterations were detected via RNA sequencing. RT-qPCR and Western blot were employed to validate gene and protein expression in HCECs and mouse corneal epithelia. Proteomic analysis was conducted on tear samples from patients. FML treatment significantly inhibited CEC proliferation, migration, and wound healing. At the molecular level, FML treatment led to a remarkable downregulation of RhoA, Rac1, and Cdc42. Correspondingly, reductions in the downstream Erk and NF-κB signaling pathways were observed in both HCECs and mouse corneal epithelia. Moreover, these pathways were similarly downregulated in tear samples from clinical patients. In conclusion, FML inhibits CEC proliferation and migration by modulating the Rho GTPase signaling network, especially through RhoA/Rac1/Cdc42, thereby suppressing the Erk/NF-κB pathway.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110397"},"PeriodicalIF":3.0,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881442","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}
Yibin Tian , Zipei Luo , Dajiang Lu , Cheng Liu , Christine Wildsoet
{"title":"Reconstruction of highly and extremely aberrated wavefront for ocular Shack-Hartmann sensor using multi-task Attention-UNet","authors":"Yibin Tian , Zipei Luo , Dajiang Lu , Cheng Liu , Christine Wildsoet","doi":"10.1016/j.exer.2025.110394","DOIUrl":"10.1016/j.exer.2025.110394","url":null,"abstract":"<div><div>In certain ocular conditions, such as in eyes with keratoconus or after corneal laser surgery, Higher Order Aberrations (HOAs) may be dramatically elevated. Accurately recording interpretable wavefronts in such highly aberrated eyes using Shack-Hartmann sensor is a challenging task. While there are studies that have applied deep neural networks to Shack-Hartmann wavefront reconstructions, they have been limited to low resolution and small dynamic range cases. In this study, we introduce a multi-task learning scheme for High-Resolution and High Dynamic Range Shack-Hartmann wavefront reconstruction using a modified attention-UNet (HR-HDR-SHUNet), which outputs a wavefront map along with Zernike coefficients simultaneously. The HR-HDR-SHUNet was evaluated on three large datasets with different levels of HOAs (regularly, highly, and extremely aberrated), with successful reconstruction of all aberrated wavefronts, at the same time achieving significantly higher accuracy than both traditional methods and other deep learning networks; it is also computationally more efficient than the latter.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110394"},"PeriodicalIF":3.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143870473","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}
Renhao Zhong , Lihua Kang , Wenjing Geng, Linhui Xu, Pengfei Li, Miaomiao Wu, Guowei Zhang, Mengying Zhou, Kai Zhang, Min Ji, Huaijin Guan
{"title":"APEX1 attenuates ERS-induced paraptosis by inhibiting the P53 pathway in LECs","authors":"Renhao Zhong , Lihua Kang , Wenjing Geng, Linhui Xu, Pengfei Li, Miaomiao Wu, Guowei Zhang, Mengying Zhou, Kai Zhang, Min Ji, Huaijin Guan","doi":"10.1016/j.exer.2025.110393","DOIUrl":"10.1016/j.exer.2025.110393","url":null,"abstract":"<div><div>Age-related cortical cataract (ARCC) is a prominent subtype of cataract, characterized by the presence of vacuoles and spoke-like opacity. Previous studies have suggested that paraptosis is involved in the onset of early ARCC vacuolar degeneration. In this experiment, hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced SRA01/04 cells were used to establish a paraptosis-like cell model, and the function and underlying mechanism of APEX1 in this cell model were explored. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western Blot analyses were conducted to assess the expression of pertinent genes in SRA01/04. Confocal fluorescence microscopy, using ER-tracker kits, was applied to clarify the relationship between the endoplasmic reticulum and intracellular vacuoles. The co-IP assay was used to verify the interaction between APEX1 and P53. The GTRD database was employed to predict the putative target genes combined with P53, and CUT&RUN assay was employed to confirm the enrichment of the P53 and ATF6 promoters following APEX1 overexpression. Firstly, the pathological sections of the vacuolar degeneration zone in the lens cortex of ARCC patients exhibited fiber disarray and vacuole development. Meanwhile, the protein expression of Alix, a specific paraptosis inhibitor, was decreased in low-concentration H<sub>2</sub>O<sub>2</sub>-treated SRA01/04 cells. Secondly, we discovered that 4-PBA suppressed the expression of ATF6 and PERK. Moreover, overexpression of APEX1 in SRA01/04 cells improved endoplasmic reticulum morphology, inhibited the interaction between P53 and ATF6, and attenuated paraptosis in SRA01/04. APEX1 regulated P53 and then mediated ATF6 to affect the endoplasmic reticulum stress and paraptosis in H<sub>2</sub>O<sub>2</sub>-induced SRA01/04 cells.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110393"},"PeriodicalIF":3.0,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859823","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}
Mehmet Gurdal , Kemal Baysal , Ismet Durak , Ozlem Barut Selver
{"title":"Limbal explant cultures on amniotic membrane: The effects of passaging the explants on cell phenotype","authors":"Mehmet Gurdal , Kemal Baysal , Ismet Durak , Ozlem Barut Selver","doi":"10.1016/j.exer.2025.110392","DOIUrl":"10.1016/j.exer.2025.110392","url":null,"abstract":"<div><div><em>In vitro</em> expansion of limbal epithelial stem cells (LESCs) while maintaining their characteristics has the potential to address the urgent need in ophthalmology clinics for the treatment of limbal stem cell deficiency (LSCD). Herein, we investigated the impact of explant passaging on the phenotype of LESCs cultured on human amniotic membrane (hAM). Following initial coverage of the hAM surface by cells (passage 0), the rabbit limbal explants underwent two additional passages. Expanded cells were then counted using a hemocytometer and examined by immunocytochemistry and RT-qPCR to assess markers associated with LESCs (ABCG2, P63, CK14, CXCR4, BMI-1, and vimentin) and differentiated LESCs (CK3 and connexin 43). The cell yield of passage 1 was the highest among all passages. Immunocytochemistry analysis revealed that the number of CK14-positive cells was similar across all passages; vimentin-positive cells were the lowest in passage 0, while vimentin-positive cells were the highest in passage 1; and CK3-positive cells were the highest in passage 0. RT-qPCR analysis revealed that CK3 and connexin 43 expression was significantly higher in passage 0 cells than in passage 2 cells; and CXCR4 and BMI-1 expressions were significantly higher in passage 1 cells than in passage 0 cells. Our data highlight that the passaging of limbal explant on hAM results in varying cell characteristics. The decrease in CK3 and increase in ABCG2 expression in cells obtained by passaging the limbal explant suggest that passaging could potentially enhance the stem cell population within the <em>in vitro</em> limbal explant culture on hAM.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110392"},"PeriodicalIF":3.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843749","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}
Chao Cheng , Yan Zong , Fang Duan , Ziyan Chen , Xiuping Liu , Kaili Wu
{"title":"Identification of herpes simplex virus type 1 infection by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry","authors":"Chao Cheng , Yan Zong , Fang Duan , Ziyan Chen , Xiuping Liu , Kaili Wu","doi":"10.1016/j.exer.2025.110391","DOIUrl":"10.1016/j.exer.2025.110391","url":null,"abstract":"<div><div>This study aimed to investigate whether Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) could identify Herpes simplex virus type 1 (HSV1) infection in samples <em>in vitro</em> and <em>in vivo</em>. MS spectra of supernatants and suspensions from infected human cornea epithelial (HCE) cell culture samples and infected samples of BALB/c mouse corneas were obtained by a VITEK® mass spectrometer. The discriminating peaks between infected and non-infected samples were used to establish discriminating superspectra (DSPc for cells and DSPm for corneas) by SARAMIS™ software. Another infected cells with two viral titers and infected cornea samples were used for blind testing against two DSPs. The results showed that automatic matching by the SARAMIS system revealed 28 discriminating peaks in HSV1-infected cells and 17 discriminating peaks in HSV1 keratitis, generating two discriminating superspectra (DSPs). Blind testing of virus-infected samples demonstrated a high positive identification rate for both <em>in vitro</em> and <em>in vivo</em> DSPs. The positive identification rate varied with viral titers, with cell suspensions exhibiting significantly higher rates compared to supernatants. Cluster analysis based on MS spectra revealed that there were more obvious differences between <em>in vivo</em> and <em>in vitro</em> samples compared to the differences between infected and non-infected samples. These findings suggest that MALDI-TOF MS can directly identify HSV1 <em>in vitro</em> or <em>in vivo</em> infected specimens, with higher positivity rates achieved when using cellular suspensions directly. This is an attempt on the method of virus detection, which shows potential for using MS to detect HSV1 infection or other virus infection in humans.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110391"},"PeriodicalIF":3.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850357","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}
Xiaoyang Xue , Xiaochuan Duan , Mengyuan Qin , Shoukuan Liu , Lin Su , Xin Cao , Hongquan Duan , Boshi Liu , Tianwen Ni , Xiaorong Li
{"title":"Topical application of Cap-loaded hydrogels inhibits corneal neovascularization","authors":"Xiaoyang Xue , Xiaochuan Duan , Mengyuan Qin , Shoukuan Liu , Lin Su , Xin Cao , Hongquan Duan , Boshi Liu , Tianwen Ni , Xiaorong Li","doi":"10.1016/j.exer.2025.110390","DOIUrl":"10.1016/j.exer.2025.110390","url":null,"abstract":"<div><div>Corneal neovascularization (CNV) is a significant risk factor for visual impairment. The efficiency and side effects of current CNV treatments, such as steroids and antivascular endothelial growth factor agents, are still debated. In addition, the bioavailability of topical drugs is usually hindered by tears, blinking, and the corneal anatomy. Therefore, finding a new therapeutic strategy is important. This study aimed to examine the function of the new therapeutic agent capmatinib (Cap), a highly selective inhibitor of MET that plays an important role in angiogenesis, in treating CNV. In this study, we first investigated the role of the HGF/c-MET axis in CNV and the therapeutic effect of Cap in a corneal alkali burn model. We synthesised a genipin-crosslinked gelatine-based hydrogel containing Cap (Cap-Gel). We observed a more significant therapeutic effect with the Cap-Gel than with Cap alone, as well as the alleviation of inflammatory infiltration and fibrosis. On day 14, the Cap-Gel group showed the most significant inhibition of corneal neovascularization, with the shortest neovessel length (0.48 ± 0.13 mm), smallest CNV area (3.77 ± 0.78 mm<sup>2</sup>), and lowest clinical assessment score (3.33 ± 0.52). Taken together, our results suggest that Cap-Gel could be a promising drug candidate for treating CNV.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110390"},"PeriodicalIF":3.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859822","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}
Rong Zhang , Ning Li , Yuanfu Fan , Dai Qing , Sijie Zhao , Xiaohui Ren , Aiqin Wang , Ziqing Gao , Yuchen Fan
{"title":"A multi-omics study reveals molecular characteristics and therapeutic targets of salidroside in reducing TGF-β2-induced ECM expression","authors":"Rong Zhang , Ning Li , Yuanfu Fan , Dai Qing , Sijie Zhao , Xiaohui Ren , Aiqin Wang , Ziqing Gao , Yuchen Fan","doi":"10.1016/j.exer.2025.110386","DOIUrl":"10.1016/j.exer.2025.110386","url":null,"abstract":"<div><div>Primary open-angle glaucoma (POAG) is a leading cause of irreversible blindness worldwide, driven by elevated intraocular pressure (IOP) due to trabecular meshwork (TM) fibrosis, extracellular matrix (ECM) accumulation, and increased aqueous humor outflow resistance. Transforming growth factor-beta 2 (TGF-β2) promotes the expression of fibrosis-related genes, exacerbating these effects. Salidroside, a bioactive compound, has been shown to inhibit TGF-β2-induced ECM expression and alleviate ocular hypertension. However, its underlying molecular mechanisms remain unclear. This study explores the transcriptional, proteomic, and metabolic changes in human TM cells treated with TGF-β2 and salidroside. Human TM cells were treated with TGF-β2 (5 ng/mL) for 48 h, followed by salidroside (30 μM) for 24 h. Multi-omics analyses, including transcriptomics, label-free proteomics, and non-targeted metabolomics, were performed to identify differentially expressed genes (DEGs), proteins (DEPs), and metabolites. The results revealed that TGF-β2 inhibited HTM cell metabolism, affecting pathways like the TCA cycle. Salidroside restores balance by regulating 15 key biomolecules, including MELTF and SLC25A10, through dual-level and post-translation mechanisms. ROC and docking analyses highlight salidroside's role in enhancing metabolic transport and energy activity, with SLC25A10 also linked to RNA processing, showcasing its therapeutic potential. These findings provide valuable insights into POAG pathogenesis and the therapeutic potential of salidroside, offering a foundation for the future development of novel treatment strategies targeting transcriptional, translational, and metabolic dysregulation in POAG.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"256 ","pages":"Article 110386"},"PeriodicalIF":3.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876932","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}
Timur Mavlyutov, Samer E. Bilal, Justin J. Myrah, Kelsey M. Mathers, Taylor Y. Lee, Colleen M. McDowell
{"title":"TGFβ2 alters segmental outflow and ECM ultrastructure in the trabecular meshwork","authors":"Timur Mavlyutov, Samer E. Bilal, Justin J. Myrah, Kelsey M. Mathers, Taylor Y. Lee, Colleen M. McDowell","doi":"10.1016/j.exer.2025.110377","DOIUrl":"10.1016/j.exer.2025.110377","url":null,"abstract":"<div><div>TGFβ2 is a well-known contributor to extracellular matrix (ECM) changes in the trabecular meshwork (TM). TGFβ2 is increased in the aqueous humor (AH) of primary open angle glaucoma patients and the addition of TGFβ2 to primary human TM cells in culture induces pathogenic changes similar to what is seen in the TM of ocular hypertensive and glaucomatous eyes. Overexpression of a bioactivated form of TGFβ2 using adenovirus 5 (Ad5.TGFβ2) in the TM has previously been described as an inducible mouse model of ocular hypertension and has been utilized for multiple studies to help understand the pathogenies of TGFβ2-induced TM damage and elevated intraocular pressure (IOP). Ad5.TGFβ2 is known to elevate IOP, decrease outflow facility, and increase expression of ECM proteins in the TM. Here, we further analyze the effects of overexpression of TGFβ2 by Ad5 in the TM. We found Ad5.TGFβ2 increases expression of macrophage marker Iba1 and increases expression of ECM proteins fibronectin and collagen 1 compared to Ad5.Null injected controls. In addition, overexpression of TGFβ2 by Ad5 led to a decrease in segmental AH flow regions compared to Ad5.Null control eyes. Ultrastructure analysis of the Ad5.TGFβ2 injected eyes also show significantly more areas occupied by ECM material as well as the development of more smaller giant vacuoles compared to Ad5.Null injected eyes. These data in combination with prior research using Ad5.TGFβ2, establish the use of intraocular injection of Ad5.TGFβ2 as an appropriate mouse model of ocular hypertension to study aqueous humor outflow and its mechanisms.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"255 ","pages":"Article 110377"},"PeriodicalIF":3.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143824195","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}