Experimental eye research最新文献

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Diabetic retinopathy as a sentinel of systemic vascular dysfunction: Shared molecular mechanisms with cardiovascular disease 糖尿病视网膜病变作为全身血管功能障碍的前哨:与心血管疾病共享的分子机制。
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-18 DOI: 10.1016/j.exer.2025.110644
Ting Wang, Hongyu Li, Chuyao Wang, Xiuyun Li, Aijun Deng, Xinwei Jiao
{"title":"Diabetic retinopathy as a sentinel of systemic vascular dysfunction: Shared molecular mechanisms with cardiovascular disease","authors":"Ting Wang,&nbsp;Hongyu Li,&nbsp;Chuyao Wang,&nbsp;Xiuyun Li,&nbsp;Aijun Deng,&nbsp;Xinwei Jiao","doi":"10.1016/j.exer.2025.110644","DOIUrl":"10.1016/j.exer.2025.110644","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) and cardiovascular disease (CVD) represent interconnected complications of diabetes, bound by overlapping pathophysiological processes and epidemiological correlations. This review explores their interplay, highlighting hyperglycemia-driven oxidative stress, chronic inflammation, endothelial dysfunction, and advanced glycation end-products (AGEs)-receptor for AGEs (RAGE) axis activation, which contribute to retinal microvascular damage and systemic atherosclerosis. Severe DR markedly increases CVD risk, positioning it as a marker of vascular pathology. Therapies targeting these pathways, including intensive glycemic control, glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), fenofibrate, and renin-angiotensin-aldosterone system (RAAS) inhibitors, offer dual benefits, slowing DR progression and reducing CVD events. Multidisciplinary strategies integrating retinal screening with CVD risk management enhance patient care. Challenges include clarifying causality and improving risk tools. Future research should prioritize causal mechanisms, biomarkers, and personalized treatments to prevent vision loss and cardiovascular morbidity in diabetes.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110644"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091630","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}
引用次数: 0
OcuMDNet: A lightweight CNN for robust multi-disease retinal diagnosis with cross-dataset reliability OcuMDNet:一种轻量级的神经网络,用于鲁棒多疾病视网膜诊断,具有跨数据集可靠性。
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-18 DOI: 10.1016/j.exer.2025.110642
Qianjie Yang , Vijay Govindarajan , Qiyuan Li , Heding Zhou , Zaffar Ahmed Shaikh , Amel Ksibi , Jing Yang , Lip Yee Por
{"title":"OcuMDNet: A lightweight CNN for robust multi-disease retinal diagnosis with cross-dataset reliability","authors":"Qianjie Yang ,&nbsp;Vijay Govindarajan ,&nbsp;Qiyuan Li ,&nbsp;Heding Zhou ,&nbsp;Zaffar Ahmed Shaikh ,&nbsp;Amel Ksibi ,&nbsp;Jing Yang ,&nbsp;Lip Yee Por","doi":"10.1016/j.exer.2025.110642","DOIUrl":"10.1016/j.exer.2025.110642","url":null,"abstract":"<div><div>This study aims to develop a lightweight convolutional network for the classification of multiple retinal diseases using fundus images and to evaluate cross-dataset generalization under strict label alignment. We introduce OcuMDNet (Ocular Multi-Disease Net), a compact convolutional neural network (CNN) specifically designed for fundus imagery, incorporating batch normalization and dropout for regularization. A standardized processing pipeline is employed, which includes cropping and resizing images to 224 × 224 pixels, applying contrast-limited adaptive histogram equalization (CLAHE), and performing per-channel normalization. The training process utilizes the AdamW optimizer and incorporates early stopping to enhance model performance. We propose a label-aligned evaluation protocol: (i) assesses 4-class performance (Normal, diabetic retinopathy (DR), Glaucoma, age-related macular degeneration (AMD)) on a combined dataset assembled from public sources; (ii) reports disease-specific results based on the native labels of each dataset (DR: EyePACS, Messidor; Glaucoma: ORIGA; AMD: AREDS); and (iii) evaluates cross-dataset transfer for DR (training on EyePACS and testing on Messidor). Patient-level splits are implemented to prevent data leakage, and class counts are reported for each split. Performance metrics such as accuracy, macro-F1 score, and one-vs-rest ROC-AUC are calculated with 95 % confidence intervals using stratified bootstrap (n = 1000). Paired comparisons are conducted using McNemar's test for accuracy and DeLong's method for AUC, with multiplicity control applied. The OcuMDNet demonstrates strong performance on both combined and disease-specific benchmarks, maintaining robust discrimination in cross-dataset evaluations for DR while ensuring computational efficiency suitable for large-scale screening applications. Ablation studies confirm the significance of preprocessing steps and architectural choices. In conjunction with a label-aligned protocol, the OcuMDNet provides an accurate and efficient baseline for multi-disease fundus analysis, facilitating a transparent assessment of cross-dataset reliability. The code, scripts, and trained weights will be made available to support reproducibility.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110642"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102908","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}
引用次数: 0
Examining murine eye length asymmetry with spectral domain optical coherence tomography 用光谱域光学相干断层扫描检测小鼠眼长不对称性。
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-18 DOI: 10.1016/j.exer.2025.110648
Linjiang Lou , Katelyn M. Hall , Machelle T. Pardue
{"title":"Examining murine eye length asymmetry with spectral domain optical coherence tomography","authors":"Linjiang Lou ,&nbsp;Katelyn M. Hall ,&nbsp;Machelle T. Pardue","doi":"10.1016/j.exer.2025.110648","DOIUrl":"10.1016/j.exer.2025.110648","url":null,"abstract":"<div><div>The mouse is an increasingly popular model for examining refractive development, however measuring axial length in the small mouse eye is challenging. We measured ocular axial dimensions with spectral domain optical coherence tomography (SD-OCT) and examined how ocular dimensions vary with alignment of the SD-OCT system in a mouse model of lens-induced myopia. Refractive error, corneal radius of curvature, and ocular dimensions were measured in C57BL/6J mice from P25 to P46. Mice received monocular lens treatment with either a −10D (n = 14) or −30D lens (n = 13) at P28 or had no lens treatment (n = 14). OCT images were taken at different eccentricities in the temporal, nasal, inferior, and superior quadrants of the eye. Axial length, vitreous chamber depth (VCD), and anterior chamber depth decreased with increasing eccentricity (P &lt; 0.001), whereas lens thickness increased with greater eccentricity (P &lt; 0.001). Axial length and VCD were longer in the superior and temporal quadrants compared to the nasal and inferior quadrants (P &lt; 0.001). The −30D lens induced a greater myopic shift compared to the −10D lens (P &lt; 0.001). Both lenses induced a steeper corneal curvature compared to the contralateral eye (P &lt; 0.01). There were no significant differences in ocular dimensions between lens treatment groups, quadrants, or eccentricities (P &gt; 0.05). Changes in corneal radius of curvature could predict the myopic shift observed with lens treatment. Findings suggest that there are significant differences in axial length measurements depending on the alignment of the OCT system. Thus, consistent alignment to the same region is important for accurate comparison of axial length in mouse eyes with experimental myopia.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110648"},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102891","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}
引用次数: 0
How sleep disturbance promotes myopia: A perspective on potential biological mechanisms 睡眠障碍如何促进近视:潜在生物学机制的视角。
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-17 DOI: 10.1016/j.exer.2025.110645
Siyang Liu , Xingtao Zhou , Jing Zhao
{"title":"How sleep disturbance promotes myopia: A perspective on potential biological mechanisms","authors":"Siyang Liu ,&nbsp;Xingtao Zhou ,&nbsp;Jing Zhao","doi":"10.1016/j.exer.2025.110645","DOIUrl":"10.1016/j.exer.2025.110645","url":null,"abstract":"<div><div>Myopia is an urgent public health concern. However, its pathogenesis remains unclear. Sleep disturbance is a potential environmental risk factor for myopia; however, the underlying mechanisms linking sleep and myopia remain largely unexplored. This review outlines three pathways through which sleep disturbance may contribute to the onset and progression of myopia. First, disruption of the circadian rhythm associated with sleep disturbance alters retinal dopamine dynamics and the balance between dopamine receptor subtypes, ultimately promoting myopia, with melatonin and intrinsically photosensitive retinal ganglion cells likely mediating this effect. Second, reduced choroidal blood flow caused by increased sympathetic tone during sleep disturbance may induce scleral hypoxia and myopic changes. Third, ocular inflammation triggered by sleep disturbance may further accelerate myopia progression. Elucidating these mechanisms could guide the development of targeted preventive and therapeutic strategies. Future studies should use well-designed animal models with sleep interventions to elucidate these mechanisms.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110645"},"PeriodicalIF":2.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091650","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}
引用次数: 0
Panoramic view of retinal and choroidal circulation and structures in vivo based on ultra-widefield OCT/OCTA: from animal to human 基于超宽视场OCT/OCTA的视网膜和脉络膜循环和体内结构全景图:从动物到人类。
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-17 DOI: 10.1016/j.exer.2025.110641
Chen Chen , Jinlian Zhan , Tong Wang , Yunyi Liu , Lanqi Du , Yaoyang He , Mary Ho , Marten E. Brelen , Lin Lu , Shida Chen
{"title":"Panoramic view of retinal and choroidal circulation and structures in vivo based on ultra-widefield OCT/OCTA: from animal to human","authors":"Chen Chen ,&nbsp;Jinlian Zhan ,&nbsp;Tong Wang ,&nbsp;Yunyi Liu ,&nbsp;Lanqi Du ,&nbsp;Yaoyang He ,&nbsp;Mary Ho ,&nbsp;Marten E. Brelen ,&nbsp;Lin Lu ,&nbsp;Shida Chen","doi":"10.1016/j.exer.2025.110641","DOIUrl":"10.1016/j.exer.2025.110641","url":null,"abstract":"<div><div>This study aimed to compare retinal and choroidal circulation and structural parameters between humans and five commonly used experimental animals (rats, mice, guinea pigs, rabbits, and monkeys) using ultra-widefield swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA). The study found that the six species exhibited unique patterns in retinal and choroidal vessel flow distribution. Rats and mice demonstrated significantly higher retinal and choroidal vessel flow density (VFD) compared to humans, while retinal vessels in rabbits are confined to a broad horizontal band, and in guinea pigs are restricted to the peripapillary area. Monkeys displayed retinal vessel flow patterns highly similar to humans, but with a higher vessel flow density in the deep capillary plexus (DCP) within the central region. Retinal and choroidal thicknesses were consistently thinner in rodents and rabbits than in humans, and monkeys displayed a thinner inner retinal layer (IRL) and choroid in the central region. Regarding optic nerve head parameters, both monkeys and rabbits showed smaller optic cup area and rim area compared to humans. However, no significant difference in the cup-to-disc ratio (CDR) was observed between humans and monkeys, whereas rabbits exhibited a significantly higher CDR. These results demonstrate significant interspecies variations in retinal and choroidal circulation, thickness, and optic nerve head structure. The findings provide a reference framework for the careful selection of animal models in ophthalmic research, facilitating a better understanding and application of these models to simulate human ocular diseases.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110641"},"PeriodicalIF":2.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091206","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}
引用次数: 0
Phytic acid protects corneal endothelium from UVA induced ferroptosis 植酸保护UVA诱导的角膜内皮细胞铁下垂。
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-17 DOI: 10.1016/j.exer.2025.110647
Meng Zhou , Weijie Zhang , Chunlei Zhang , Yao Fu , Hao Sun
{"title":"Phytic acid protects corneal endothelium from UVA induced ferroptosis","authors":"Meng Zhou ,&nbsp;Weijie Zhang ,&nbsp;Chunlei Zhang ,&nbsp;Yao Fu ,&nbsp;Hao Sun","doi":"10.1016/j.exer.2025.110647","DOIUrl":"10.1016/j.exer.2025.110647","url":null,"abstract":"<div><div>Corneal endothelial decompensation is a common vision-threatening disease, with a diverse range of pathogenic factors, ultimately necessitating corneal transplantation. Corneal endothelial cells (CECs) act as a barrier between the aqueous humor and stroma, and are non-proliferative <em>in vivo</em>. CECs are susceptible to oxidative stress damage due to their lifelong high metabolic state, which enables them to constantly pump liquid to maintain the dehydrated status of the cornea. Consequently, CECs are subjected to the accumulation of oxidative stress over time, which can result in cell death in the form of apoptosis. In this study, we identified ferroptosis of CECs as a nonapoptotic pathological process in the ultraviolet A (UVA)-mediated corneal endothelial decompensation, confirmed by the production of lipid peroxidation and the observed morphological changes in the mitochondria. The process was mediated by the promotion of nuclear export of nuclear erythroid 2-related factor 2 (Nrf-2). In addition, we identified for the first time that a natural iron chelator, phytic acid (PA), could protect CEC from UVA-mediated ferroptosis and helped to maintain the function of corneal endothelium. Our findings suggest that PA has the potential as a therapeutic agent for the treatment of corneal endothelial decompensation.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110647"},"PeriodicalIF":2.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091267","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}
引用次数: 0
SPG302 protects retinal ganglion cells and preserves visual function by preserving synaptic activity in a mouse model of glaucoma SPG302通过维持青光眼小鼠模型的突触活性来保护视网膜神经节细胞和视觉功能。
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-16 DOI: 10.1016/j.exer.2025.110640
Tonking Bastola , Seunghwan Choi , Ziyao Shen , Keun-Young Kim , Peter W. Vanderklish , Stella T. Sarraf , Jiun L. Do , Alex S. Huang , Robert N. Weinreb , Won-Kyu Ju
{"title":"SPG302 protects retinal ganglion cells and preserves visual function by preserving synaptic activity in a mouse model of glaucoma","authors":"Tonking Bastola ,&nbsp;Seunghwan Choi ,&nbsp;Ziyao Shen ,&nbsp;Keun-Young Kim ,&nbsp;Peter W. Vanderklish ,&nbsp;Stella T. Sarraf ,&nbsp;Jiun L. Do ,&nbsp;Alex S. Huang ,&nbsp;Robert N. Weinreb ,&nbsp;Won-Kyu Ju","doi":"10.1016/j.exer.2025.110640","DOIUrl":"10.1016/j.exer.2025.110640","url":null,"abstract":"<div><div>Glaucoma, a leading cause of irreversible vision loss worldwide, is an optic neuropathy characterized by optic nerve degeneration and retinal ganglion cell (RGC) death. Early glaucomatous damage is often associated with dendritic and synaptic abnormalities in RGCs, yet the mechanisms linking these synaptic alterations to RGC death remain unclear. In a mouse model of glaucoma, treatment with the clinical-stage, synaptogenic small molecule SPG302, a pegylated benzothiazole derivative, demonstrated neuroprotective effects, protecting RGCs and their axons in the glaucomatous retina and also improving retinal function as assessed by pattern electroretinogram testing. Elevated intraocular pressure disrupted synapses, as evidenced by reduced synaptophysin expression and homeostatic increases in Bassoon and PSD95 levels in the inner plexiform layer. SPG302 treatment effectively preserved synaptic integrity by reversing these changes. These findings highlight the therapeutic potential of SPG302 for protecting RGCs and preserving vision by modulating synaptic activity in glaucomatous neurodegeneration.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110640"},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085493","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}
引用次数: 0
Remodelling of smooth endoplasmic reticulum of Müller cells in aged human retina 老龄人视网膜上皮细胞光滑内质网的重构。
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-12 DOI: 10.1016/j.exer.2025.110634
Tapas C. Nag
{"title":"Remodelling of smooth endoplasmic reticulum of Müller cells in aged human retina","authors":"Tapas C. Nag","doi":"10.1016/j.exer.2025.110634","DOIUrl":"10.1016/j.exer.2025.110634","url":null,"abstract":"<div><div>The smooth endoplasmic reticulum (SER) is a system of interconnected cytoplasmic tubules with various subdomains, which can remodel in response to certain stimuli, as in the retinal pigment epithelium. Earlier studies reported Müller cells (MC) to contain the SER tubules as the main subdomain. A routine examination of postmortem human retinas (54–94 years; N = 8) revealed diverse SER subdomains in aged MC. Besides the presence of tubules with a distinct lumen, MC possessed tubules that were rather compressed, with partial to fully obliterated lumen. The other SER subdomains detected were lamellar and whorl that assembled near the endfeet plasma membrane. The compressed SER were quite longer, often curved and detected in MC endfeet and outer processes in Henle's fiber layer of aged macula (&gt;80 years). No such features were detected in any cells of the peripheral retina nor in young donor retinas examined. Because lipid peroxidation was prominent in macular MC, it may be involved in the remodelling of SER shape. While the organized lamellar and whorl subdomains can be related to certain physiological demands, the peculiar SER subdomains with obliterated lumen could limit the normal functions of SER, e.g., calcium storage and carbohydrate metabolism.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110634"},"PeriodicalIF":2.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063821","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}
引用次数: 0
Distinct transcriptional regulation of the Wnt and TGFβ signaling families associated with wound healing and fibrotic outcomes to lens injury Wnt和TGFβ信号家族与晶状体损伤的伤口愈合和纤维化结果相关的独特转录调控
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-12 DOI: 10.1016/j.exer.2025.110628
Catherine Lalman , Kylie R. Stabler , Joshua Disatham , Lisa A. Brennan , Marc Kantorow , Janice L. Walker
{"title":"Distinct transcriptional regulation of the Wnt and TGFβ signaling families associated with wound healing and fibrotic outcomes to lens injury","authors":"Catherine Lalman ,&nbsp;Kylie R. Stabler ,&nbsp;Joshua Disatham ,&nbsp;Lisa A. Brennan ,&nbsp;Marc Kantorow ,&nbsp;Janice L. Walker","doi":"10.1016/j.exer.2025.110628","DOIUrl":"10.1016/j.exer.2025.110628","url":null,"abstract":"<div><div>Posterior capsule opacification (PCO) is a fibrotic complication of cataract surgery caused by aberrant repair of residual lens cells. It remains unclear how the lens injury response shifts toward a pathological repair process. Here, we performed a transcriptional analysis of two major pro-fibrotic pathways, the TGF-β superfamily and Wnt signaling pathways to determine how they are differentially regulated during regenerative wound healing versus fibrosis in a lens injury model. For these studies, RNA sequencing was performed on an ex vivo lens explant system that models post-surgical healing within regenerative and fibrotic microenvironments, from 0 to 3 days post-injury. Fibrotic conditions were marked by increased expression of TGF-β ligands, receptors, SMAD3, and extracellular regulators, LTBP1 and THSB1 consistent with strong activation of canonical TGF-β signaling. In contrast, BMP signaling during wound healing, was characterized by early induction of BMP receptors, SMAD1, and downstream ID genes, indicative of robust activation while in fibrosis, BMP ligands and receptors increased but downstream signaling was blunted potentially by elevated expression of BMP inhibitors. Inhibition of ID proteins using a pan-ID inhibitor, impaired both wound closure and myofibroblast formation, supporting a role for ID protein function in both contexts. Distinct Wnt ligands and FZD receptors were upregulated in regenerative vs. fibrotic repair contexts to drive canonical/noncanonical Wnt signaling. Fibrosis favored upregulation of the Wnt/Ca<sup>2+</sup> pathway and multiple RSPO's associated with Wnt activation. These findings reveal new insight into the transcriptional regulation of the TGF-β and Wnt family pathway components and modulators associated with programming distinct outcomes to lens injury.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110628"},"PeriodicalIF":2.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063788","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}
引用次数: 0
Subtle retinal degeneration in pigmented Abca4−/− Rdh8−/− mice Abca4-/- rdh8 -/-小鼠视网膜细微变性
IF 2.7 2区 医学
Experimental eye research Pub Date : 2025-09-11 DOI: 10.1016/j.exer.2025.110639
Sarah Glänzer, Josef Biber, Antje Grosche
{"title":"Subtle retinal degeneration in pigmented Abca4−/− Rdh8−/− mice","authors":"Sarah Glänzer,&nbsp;Josef Biber,&nbsp;Antje Grosche","doi":"10.1016/j.exer.2025.110639","DOIUrl":"10.1016/j.exer.2025.110639","url":null,"abstract":"<div><div>Stargardt disease type 1 is a genetic retinal disorder caused by mutations in the <em>ABCA4</em> gene, leading to toxic bisretinoid accumulation in the retinal pigment epithelium (RPE). This study examines the retinal phenotype of <em>Abca4</em><sup>−/−</sup> <em>Rdh8</em><sup>−/−</sup> double knockout mice on a C57BL/6J background, excluding confounding variants such as the <em>Rpe65</em> Leu450Met variant or the rd8 mutation in the <em>Crb1</em> gene, to define the effect of combined Abca4 and Rdh8 deficiency.</div><div>Double knockout mice—confirmed free of the rd8 mutation and to not carry the protective Met variant of the <em>Rpe65</em> gene—were analyzed at 4 and 9 months and compared to <em>Rdh8</em><sup><em>−/−</em></sup> single knockouts under varying light exposure. Histological assessments included RPE autofluorescence, morphometric parameters of microglial activation, and retinal layer integrity.</div><div>At 4 months, no significant structural differences were observed between genotypes. By 9 months, <em>Abca4</em><sup>−/−</sup> <em>Rdh8</em><sup>−/−</sup> mice showed increased RPE autofluorescence, consistent with elevated bisretinoid accumulation. Four-fold enhanced light exposure affected microglial morphology, and a modest age-related thinning of retinal layers was noted in double knockouts.</div><div>In conclusion, increased RPE autofluorescence was confirmed in <em>Abca4</em><sup>−/−</sup> <em>Rdh8</em><sup>−/−</sup> mice on the C57BL/6J background, but only mild retinal structural and inflammatory changes were observed. The severe early-onset degeneration reported in prior studies was not replicated, likely due to the absence of the rd8 mutation present in the double knockout mouse strain at its original description. This suggests that the rd8 mutation drove neurodegeneration, while the combined <em>Abca4</em> and <em>Rdh8</em> deficiency alone is comparatively well tolerated in the murine retina.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"261 ","pages":"Article 110639"},"PeriodicalIF":2.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058487","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}
引用次数: 0
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