Experimental eye research最新文献

{"title":"Profiling lipidomic variations in primary open-angle and angle-closure glaucoma patients","authors":"Lakshminarayanan Gowtham ,&nbsp;Nabanita Halder ,&nbsp;Dewang Angmo ,&nbsp;Sundararajan Baskar Singh ,&nbsp;Rama Jayasundar ,&nbsp;Tanuj Dada ,&nbsp;Thirumurthy Velpandian","doi":"10.1016/j.exer.2025.110655","DOIUrl":"10.1016/j.exer.2025.110655","url":null,"abstract":"<div><div>Retinal ganglion cell death in glaucoma leads to progressive and irreversible vision loss. Investigating lipidomic profiles of aqueous humor and plasma from primary glaucoma patients may reveal novel lipid signaling pathways and biomarkers. Plasma lipidomics was included to assess systemic alterations, enabling comparison with ocular changes and explore accessible, minimally invasive biomarker sources. This study included patients with primary open-angle glaucoma (POAG), angle-closure glaucoma (PACG), and cataract controls (n = 20 in each group). Serum lipid screening was conducted via biochemical analyzer. Aqueous humor and plasma samples were collected, and lipids were extracted and analyzed using high-resolution mass spectrometry (HRMS). Spectral identification and relative quantification of lipid species were performed with LipidSearch™ver_4.1. The percentage of altered species within each lipid class was analyzed with a log₂fold change (FC) threshold ≥1/≤-1. Data normalization and multivariate statistical analyses were conducted using MetaboAnalyst 5.0 with significance criteria (log₂ FC ≥ 1/≤−1, p &lt; 0.05 and variable importance in projection (VIP) &gt; 1). No significant changes were observed in routine serum lipid profiles of glaucoma patients versus controls. In aqueous humor, phosphatidylcholines and lysophosphatidylcholines (&gt;50 %) were elevated in aqueous humor of both glaucoma groups, while sphingomyelins (&gt;85 %) and ceramides (18.75 %) were specifically elevated in PACG. Of 301 lipid species identified in aqueous humor, 51 met significance (POAG: 24, PACG: 27). In plasma, diglycerides (&gt;20 %), triglycerides and cholesterol esters (&gt;10 %, log₂FC ≤ −1) were declined in both glaucoma groups than controls. Of 1762 plasma lipids identified, 100 met significance (POAG: 47, PACG: 53). Sphingomyelin and ceramide alterations in PACG aqueous humor suggested disrupted mechanosignaling mechanisms. Altered phosphatidylcholines, lysophosphatidylcholines and glycerides linked with retinal-degeneration and apoptosis in both glaucomatous conditions.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110655"},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148337","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":"Microglia activation and migration in retina during acute high-altitude exposure","authors":"Yuting Li ,&nbsp;Cong Han ,&nbsp;Jianping Zhang ,&nbsp;Songjian Huang ,&nbsp;Xin Zhao ,&nbsp;Jiarui Zhu ,&nbsp;Qian Niu ,&nbsp;Yi Yang ,&nbsp;Wenfang Zhang","doi":"10.1016/j.exer.2025.110653","DOIUrl":"10.1016/j.exer.2025.110653","url":null,"abstract":"<div><div>High-altitude retinopathy (HAR), caused by hypobaric hypoxia, leads to retinal dysfunction. However, its pathogenic mechanism remains elusive. Microglia, the resident immune cells of the retina, play crucial roles in various retinal disorders. Here, we investigated the functional alterations and underlying mechanisms of microglial activation in mouse models exposed to high-altitude (5000m HAE). Hematoxylin and eosin (H&amp;E) staining showed edema in the entire, inner, and outer retinal layers after high-altitude exposure (HAE). Electroretinogram (ERG) testing revealed impaired retinal function under hypobaric hypoxia. Immunofluorescence staining confirmed a time-dependent increase in microglial numbers within the retina following HAE, with activated microglia migrating during persistent hypoxic injury. Furthermore, these activated microglia predominantly differentiated into pro-inflammatory subtypes under acute high-altitude conditions. Notably, Connexin43 (Cx43) immunoreactivity increased, while interleukin-1β (IL-1β) levels were markedly elevated at different time points after HAE. In this study, we confirmed that microglia activation and migration are involved in retinal edema and functional injury induced by hypobaric hypoxia. Additionally, the dynamic changes in Cx43 and up-regulation of IL-1β might be related to the inflammatory activation of microglia under acute HAE.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110653"},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120009","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":"Corrigendum to “Immune-related biomarkers in the neuromyelitis optica spectrum disorder; pathogenesis and therapeutic approaches” [Experim. Eye Res. 256 110395]","authors":"Jingyong Li ,&nbsp;Ya Dan ,&nbsp;Wei Su ,&nbsp;Mingjun Zhao ,&nbsp;Zhiguo Chen ,&nbsp;Zhuyang Zhao","doi":"10.1016/j.exer.2025.110637","DOIUrl":"10.1016/j.exer.2025.110637","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"260 ","pages":"Article 110637"},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137038","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":"Characterisation of vitreous derived small extracellular vesicles in diabetic retinopathy.","authors":"Henry H Louie, Ilva D Rupenthal, Julie C Lim, Lawrence W Chamley, Odunayo O Mugisho","doi":"10.1016/j.exer.2025.110654","DOIUrl":"10.1016/j.exer.2025.110654","url":null,"abstract":"<p><p>Diabetic retinopathy (DR) is a progressive retinal disease driven by microvascular dysfunction and inflammation, ultimately leading to vision loss. Early detection is essential for preventing irreversible damage; however, the asymptomatic nature of early-stage DR limits the effectiveness of current screening methods. Emerging evidence indicates that inflammatory processes, particularly activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome, precede clinical manifestations. Small extracellular vesicles (sEVs), which mediate intercellular communication, may serve as biomarkers by carrying NLRP3-associated proteins. This study aims to investigate the role of sEVs in DR-related inflammation. Post-mortem vitreous was obtained from donors with a confirmed DR diagnosis and compared to samples from donors with no known ocular pathology. Additionally, vitrectomy samples from DR patients were compared to samples from donors who had undergone vitrectomy for macular holes or epiretinal membranes. The concentration and size of sEVs as well as the expression of EV- and inflammasome-associated cargo markers were evaluated in both sample types using nanoparticle tracking analysis and western blotting, respectively. The results showed that the sEV concentration was higher in post-mortem and vitrectomy samples from DR patients/donors compared to controls. Furthermore, DR sEVs contained higher levels of inflammasome-related proteins than controls, indicative of increased NLRP3 inflammasome activation. Finally, we demonstrated that vitreous sEVs contained RPE-65, a protein of retinal origin, suggesting that vitreous sEVs may be derived from the retina. These findings contribute to the growing knowledge of the role of sEVs in chronic diseases and suggest that they could serve as viable biomarkers for DR.</p>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":" ","pages":"110654"},"PeriodicalIF":2.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137098","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":"YAP1 aggravates hyperglycemia-induced retinal capillary endothelial cells injury via ferroptosis and inflammation regulation","authors":"Jingying Liu ,&nbsp;Yu Cai ,&nbsp;Shijing Peng,&nbsp;Hua Zou,&nbsp;Kangcheng Liu,&nbsp;Huimin Fan,&nbsp;Zhipeng You","doi":"10.1016/j.exer.2025.110656","DOIUrl":"10.1016/j.exer.2025.110656","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is a severe vascular complication that causes blindness. Retinal capillary endothelial cells are the primary targets of DR, with ferroptosis and inflammation playing critical roles. YAP1, a downstream effector of the Hippo pathway, was recently shown to regulate ferroptosis and inflammation; however, its mechanisms in DR is not fully understood. Herein, we investigated the role of YAP1 in ferroptosis and inflammation in DR and hyperglycemia-induced human retinal capillary endothelial cells (HRCECs). The expression levels, including markers of ferroptosis and inflammation, and the nuclear localization of YAP1 were increased in diabetic retinal tissues and high glucose-treated HRCECs. YAP1 regulated ferroptosis and inflammation <em>in vitro</em>. Moreover, silencing YAP1 inhibited the high glucose-induced elevation of ACSL4, TFRC, IL-6, and TNF-α levels and the decline in GPX4 levels in HRCECs, protecting them from ferroptosis, inflammation, and oxidative stress. Conversely, YAP1 overexpression had the opposite effect. Additionally, under high glucose conditions, the ferroptosis inducer RSL3 diminished the protective effects of YAP1 silencing, while the ferroptosis inhibitor ferrostatin-1 rescued HRCECs from YAP1 overexpression-induced injury. Collectively, our results demonstrate that YAP1 is involved in DR development and mediates ferroptosis and inflammation in HRCECs under high glucose environments, providing a potential therapeutic target in DR.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110656"},"PeriodicalIF":2.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137033","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":"Comprehensive characterization of the rat magnetic microbead model using longitudinal monitoring of structural and functional parameters","authors":"Kernius Mickevičius ,&nbsp;Tomas Paulauskas ,&nbsp;Robertas Čėsna ,&nbsp;Simas Bijeikis ,&nbsp;Marius Dragašius ,&nbsp;Justina Urbanavičiūtė ,&nbsp;Symantas Ragauskas ,&nbsp;Giedrius Kalesnykas","doi":"10.1016/j.exer.2025.110651","DOIUrl":"10.1016/j.exer.2025.110651","url":null,"abstract":"<div><div>Glaucoma remains a major cause of irreversible blindness worldwide, driving the need for preclinical models that accurately replicate human disease and support the development of novel treatment methods. Intracameral microbead injection is a widely used method to induce ocular hypertension and mimic the pathophysiology of glaucoma. Most studies using this model focus on retinal ganglion cell (RGC) loss and occasionally pattern electroretinography (pERG) for functional assessment of RGC. In our study, we broaden model characterization by incorporating behavioral, functional, and morphological assessments using <em>in vivo</em> monitoring. In addition, we explored how behavioral, functional, and morphological read-outs correlated with intraocular pressure (IOP) in this model. Spectral-domain optical coherence tomography (SD-OCT) was used for quantitative evaluation of inner retinal layer (IRL) thickness. PERG was recorded to assess RGC function. Optomotor tracking was performed to evaluate visual acuity (VA) and contrast sensitivity (CS). After 4 weeks, the animals were euthanized, and retinal wholemounts with optic nerves were collected for RGC quantification and axon assessment. As expected, we found a significant thinning of IRL as confirmed by SD-OCT imaging. Additionally, pERG recordings revealed diminished RGC function, evidenced by reduced amplitude, whereas optomotor testing detected significant declines in VA and CS. Significant correlations were found between IOP and all parameters. The magnetic microbead-induced ocular hypertension model successfully mimicked structural and functional damage of RGCs, with early visual function declines linked to elevated IOP. Strong correlations between structural and functional parameters enhanced the translational relevance of this model in exploring new neuroprotective and regenerative therapies.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110651"},"PeriodicalIF":2.7,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145120008","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":"Enrichment analysis of polymorphic protein-coding loci associated with risk of traumatic cataract","authors":"Mostafa Saadat","doi":"10.1016/j.exer.2025.110650","DOIUrl":"10.1016/j.exer.2025.110650","url":null,"abstract":"","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110650"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102893","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":"Why brains behave differently: Insights from eye movement disorders","authors":"Aasef G. Shaikh ,&nbsp;David S. Zee","doi":"10.1016/j.exer.2025.110643","DOIUrl":"10.1016/j.exer.2025.110643","url":null,"abstract":"<div><div>The variability in the evolution, phenomenology, and response to treatment of diseases, even among patients with the same genetic mutation or identical structural or metabolic insults, is a common challenge in contemporary neurology and neuroscience. Why does the human brain react so differently to the same disease or treatment? Genetic variability among individuals might be part of the answer. Epigenetics, how the activity of genes changes with changes in the environment also contributes to the variability. Genes determine the expression profile of molecules within and on the surface of neurons, such as ion channels. This profile influences membrane physiology, which in turn affects the behavior (or misbehavior) of neural circuits and thus the disease phenomenology. The physiology of circuit behavior is extremely complex. In this context, studying eye movements is valuable because normal ocular motor physiology is better understood, the structural correlates of ocular motor disorders are clearer, and the behavioral outcomes of these disorders can be precisely measured and interpreted with mathematical models. Here, we review three disorders characterized by unwanted oscillations of the eyes. While their structural correlates are relatively well defined, the phenomenology and response to treatment of these disorders are surprisingly variable. Mathematical models suggest that the mechanisms for the diverse phenomenology of these three diseases are centered on genetically determined variability in the physiology of neuronal membranes and the internal connections of neural circuits.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110643"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100216","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":"Overexpression of cholesterol 24-hydroxylase CYP46A1 attenuates retinal dysfunction and ganglion cell loss via regulating the Nrf2 pathway in optic nerve crush injury","authors":"Zhenli Long ,&nbsp;Jun Zhang ,&nbsp;Jiazhen Feng,&nbsp;Tao He","doi":"10.1016/j.exer.2025.110649","DOIUrl":"10.1016/j.exer.2025.110649","url":null,"abstract":"<div><div>Cholesterol 24-hydroxylase CYP46A1 (CYP46A1) has been confirmed to be correlated with the processes of multiple neurological disorders, but its role in neurodegenerative optic diseases remains unclear. This article aimed to evaluate the neuroprotective effects of CYP46A1 on mouse retinal ganglion cells (RGCs) and retinal function. Mice were subjected to optic nerve crush (ONC) injury after intravitreal injection of rAAVs. RGCs' survival was quantified by immunofluorescence staining of retinal flat mounts. Retinal electrophysiological function and visual acuity were quantitatively assessed using electroretinography (ERG) and optomotor response (OMR). The TdT-mediated dUTP nick-end labeling (TUNEL) staining was employed to quantify the apoptosis of RGCs. The protein expression level of CYP46A1, B-cell lymphoma 2 (Bcl-2), BCL-2-associated X protein (Bax), Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor (Nrf2), and heme oxygenase 1 (HO1) were validated by Western blot. After ONC injury, CYP46A1 expression increased, while RGCs’ survival rate, the amplitude of photopic negative response (PhNR), and visual acuity decreased; there were no significant changes in the a-wave and b-wave. Western blotting and retinal cryosection staining confirmed that intravitreal injection of rAAV-CYP46A1-EGFP upregulated CYP46A1 expression. CYP46A1 overexpression mitigated ONC-induced RGCs loss and retinal electrophysiological dysfunction. The overexpression of CYP46A1 could significantly inhibit RGCs apoptosis, reduce Bax expression and increase Bcl-2 expression. Additionally, the upregulation of CYP46A1 led to decreased Keap1 expression and increased Nrf2 and HO-1 levels. In conclusion, our results demonstrated that the overexpression of CYP46A1 could prevent the loss of RGCs and protect the electrophysiological function by activating Nrf2 signaling pathway.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110649"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100215","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":"Rethinking the pathogenesis of meibomian gland dysfunction: Ductal-centric vs. meibocyte-centric hypothesis","authors":"Woojin Kim ,&nbsp;Dong Hyun Kim ,&nbsp;Youngsub Eom ,&nbsp;Jong Suk Song","doi":"10.1016/j.exer.2025.110646","DOIUrl":"10.1016/j.exer.2025.110646","url":null,"abstract":"<div><div>Meibomian gland dysfunction (MGD) has traditionally been explained by the ductal-centric hypothesis, which attributes disease progression to ductal obstruction and secondary acinar atrophy. However, this model does not fully account for all clinical and pathological features. Recognizing these limitations, the meibocyte-centric hypothesis has emerged, proposing that intrinsic meibocyte dysfunction and acinar degeneration may play a primary role. In this context, this narrative review incorporates selected original data from animal models to contrast the ductal-centric and meibocyte-centric hypotheses, and synthesizes current concepts of MGD pathogenesis through a comprehensive literature review. In particular, two models illustrated how ductal blockage and meibocyte injury differentially affect gland morphology. Experimental findings supporting the ductal-centric hypothesis include ductal obstruction and orifice blockage leading to secondary acinar degeneration. Observations such as gland dropout without obstruction and lid margin dimpling are not fully explained by this model. In contrast, experimental studies demonstrate that meibocyte damage leads to gland dysfunction without ductal dilatation, highlighting intrinsic cellular pathology as a complementary driver to the traditional obstruction model. In addition, immune-mediated processes are increasingly recognized as a distinct pathogenic axis that interacts with both ductal and acinar pathways. This evolving perspective carries important therapeutic implications, as current ductal-focused treatments may be insufficient to address acinar pathology. Future approaches should target both ductal and acinar compartments, with emphasis on restoring meibocyte function, modulating immune pathways, and promoting glandular regeneration.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110646"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099381","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}