Experimental eye research最新文献

{"title":"Proteomic analysis of effects of 1% atropine in myopia therapy in Guinea pigs","authors":"Chen Chu ,&nbsp;Luyao Ye ,&nbsp;Qingqing Chi ,&nbsp;Jiangnan He ,&nbsp;Jianfeng Zhu","doi":"10.1016/j.exer.2024.110224","DOIUrl":"10.1016/j.exer.2024.110224","url":null,"abstract":"<div><div>Myopia is a significant global public health issue. Key interventions for managing myopia include atropine treatment, optical correction, and surgical methods. This study focused on evaluating alterations in retinal protein expression after atropine therapy for myopia. Guinea pigs were randomly divided into four groups: control (CON), monocular form-deprivation myopia (FDM), FDM with 2-week atropine treatment (FDM + ATR), and atropine-only treatment (ATR). After two weeks of FDM induction, the FDM group showed significant differences in refractive error and increased axial lengths. In comparing the retinas of myopic and normal eyes, 30 proteins were found to have increased expression, while 8 proteins showed decreased expression. Atropine-treated retinas exhibited 73 proteins with increased expression and 29 proteins with decreased expression compared to the normal eyes. A total of 11 regulated proteins overlapped between the FDM + ATR vs FDM and FDM vs CON groups. IPA analysis indicates significant alterations in amino acid metabolism, energy production, post-translational modification, small molecule biochemistry, and free radical scavenging. Our study identifies retinal protein changes in myopic guinea pigs and in guinea pigs treated with atropine after myopia. These proteins could serve as potential targets for atropine treatment of myopia.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110224"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893276","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":"miRNAs, piRNAs, and lncRNAs: A triad of non-coding RNAs regulating the neurovascular unit in diabetic retinopathy and their therapeutic potentials","authors":"Muthuramalingam Karpagavalli ,&nbsp;Manavi D. Sindal ,&nbsp;Jayamuruga Pandian Arunachalam ,&nbsp;Subbulakshmi Chidambaram","doi":"10.1016/j.exer.2025.110236","DOIUrl":"10.1016/j.exer.2025.110236","url":null,"abstract":"<div><div>Diabetic Retinopathy (DR), a leading complication of diabetes mellitus, has long been considered as a microvascular disease of the retina. However, recent evidence suggests that DR is a neurovascular disease, characterized by the degeneration of retinal neural tissue and microvascular abnormalities encompassing ischemia, neovascularization, and blood-retinal barrier breakdown, ultimately leading to blindness. The intricate relationship between the retina and vascular cells constitutes a neurovascular unit, a multi-cellular framework of retinal neurons, glial cells, immune cells, and vascular cells, which facilitates neurovascular coupling, linking neuronal activity to blood flow. These interconnections between the neurovascular components get compromised due to hyperglycemia and are further associated with the progression of DR early on in the disease. As a result, therapeutic approaches are needed to avert the advancement of DR by acting at its initial stage to delay or prevent the pathogenesis. Non-coding RNAs (ncRNAs) such as microRNAs, piwi-interacting RNAs, and long non-coding RNAs regulate various cellular components in the neurovascular unit. These ncRNAs are key regulators of neurodegeneration, apoptosis, inflammation, and oxidative stress in DR. In this review, research related to alterations in the expression of ncRNAs and, correspondingly, their effect on the disintegration of the neurovascular coupling will be discussed briefly to understand the potential of ncRNAs as therapeutic targets for treating this debilitating disease.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110236"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970314","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":"Proteome of pericytes from retinal vasculature of diabetic donor eyes","authors":"Sharmila Rajendran ,&nbsp;Angayarkanni Narayansamy ,&nbsp;Radha Annamalai ,&nbsp;Lawrence D. Cruze ,&nbsp;Purushothaman Kathiresan ,&nbsp;Kaviarasan Kuppan","doi":"10.1016/j.exer.2024.110178","DOIUrl":"10.1016/j.exer.2024.110178","url":null,"abstract":"<div><div>Retinal pericytes (PCs) are contractile microvascular smooth muscle cells that wrap around the endothelial cells (ECs) maintaining intact retinal vasculature (RV) with a 1:1 ratio. Microvascular complications like diabetic retinopathy (DR) due to chronic diabetes causes apoptotic loss of PCs followed by diminished vessel stability, EC apoptosis, and ischemia, leading to retinal angiogenesis, and eventually severe vision loss. This study aimed to analyze the proteins in PCs isolated from the RV of diabetic human donor eyes and compare them with remaining mixed population (MP) of retinal vascular cells. PCs and MP proteomes were analyzed using semi-quantitative proteomics. Proteins were extracted, quantified, and analyzed in duplicate using LC-MS/MS on a Tandem mass spectrometer. Overall, 42 PC and 27 MP proteins, with 19 shared proteins, were identified. Functional enrichment analysis indicated that PC proteins share common biological processes, such as negative regulation of fibrinolysis and vLDL particle remodeling, nitric oxide transport, phospholipid efflux, positive control over the clearance of apoptotic cells, chondrocyte proliferation, lipoprotein lipase activity, and oxidative stress-induced intrinsic atrophic signaling pathways. In the fold enrichment analysis, the PC proteins were associated with cholesterol metabolism, Complement and coagulant, ECM-receptor interaction, longevity regulating pathway, Peroxisome proliferator-activated receptors (PPAR), focal adhesion and PI3 Akt signaling pathways. Among the PC proteins, vitronectin, gelsolin, hornerin, apolipoprotein A1, C3, H, and complement Factors C3, C4, and C9 were identified as the most highly ranked proteins in diabetes. The identified unique proteins of retinal PC could prove beneficial as a therapeutic target in the management of DR.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110178"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695322","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":"Metabolomic and transcriptomic analysis reveals metabolic-immune interactions in choroid neovascularization","authors":"Yihan Zhang ,&nbsp;Siyi Qi ,&nbsp;Weiai Shen ,&nbsp;Ying Guo ,&nbsp;Yu Liang ,&nbsp;Qiao Zhuo ,&nbsp;Hongyu Kong ,&nbsp;Shujie Zhang ,&nbsp;Chen Zhao","doi":"10.1016/j.exer.2024.110227","DOIUrl":"10.1016/j.exer.2024.110227","url":null,"abstract":"<div><div>Choroid neovascularization (CNV) is a distinct type of age-related macular degeneration (AMD) with a poor prognosis and responsible for the majority of vision loss in the elderly population. The laser-induced CNV model is a well-established animal model frequently used to study CNV. In this study, we performed an integrated analysis of metabolomic and transcriptomic data from CNV samples, utilizing multiple approaches including single-sample gene set enrichment analysis (ssGSEA), correlation analysis, and weighted gene co-expression network analysis (WGCNA), alongside various bioinformatics platforms, to identify key metabolic and immune signatures and to investigate their interplay during angiogenesis. Dominant infiltration of macrophages and monocytes was detected and a positive correlation between dysregulated riboflavin metabolism and angiogenesis pathways was characterized. Hub genes such as ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) and acid phosphatase 5, tartrate resistant (ACP5) emerged as potential central regulators of immune-metabolic crosstalk in CNV. The classification of the immune and metabolic landscape and their critical interactions in CNV models will enhance the understanding of the pathogenesis of neovascular AMD and other neovascular eye diseases, contributing to the development of multi-targeted therapeutic strategies with better efficacy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110227"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893272","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":"Oxygen-dependent alternative mRNA splicing and a cone-specific motor protein revealed by single-cell RNA sequencing in hypoxic retinas","authors":"Lynn J.A. Ebner ,&nbsp;Duygu Karademir ,&nbsp;Sarah Nötzli ,&nbsp;Gabriele M. Wögenstein ,&nbsp;Marijana Samardzija ,&nbsp;Christian Grimm","doi":"10.1016/j.exer.2024.110190","DOIUrl":"10.1016/j.exer.2024.110190","url":null,"abstract":"<div><div>Restricted oxygen supply in the aging eye may lead to hypoxic conditions in the outer retina and contribute not only to physiological aging but also to nonhereditary degenerative retinal diseases. To understand the hypoxic response of specific retinal cell types, we performed single-cell RNA sequencing of retinas isolated from mice exposed to hypoxia. Significantly upregulated expression of marker genes in hypoxic clusters confirmed a general transcriptional response to hypoxia. By focusing on the hypoxic response in photoreceptors, we identified and confirmed a kinesin motor protein (<em>Kif4</em>) that was specifically and strongly induced in hypoxic cones. In contrast, RNA-binding proteins <em>Rbm3</em> and <em>Cirbp</em> were differentially expressed across clusters but demonstrated isoform switching in hypoxia. The resulting short variants of these gene transcripts are connected to epitranscriptomic regulation, a notion supported by the differential expression of writers, readers and erasers of m⁶A RNA methylations in the hypoxic retina. Our data indicate that retinal cells adapt to hypoxic conditions by adjusting their transcriptome at various levels including gene expression, alternative splicing and the epitranscriptome. Adaptational processes may be cell-type specific as exemplified by the cone-specific upregulation of <em>Kif4</em> or general like alternative splicing of RNA binding proteins.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110190"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785065","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":"A combined experimental-computational approach for retinal characterization","authors":"Beatrice Belgio,&nbsp;Francesca Berti,&nbsp;Riccardo Tripputi,&nbsp;Federica Potere,&nbsp;Sara Mantero,&nbsp;Federica Boschetti","doi":"10.1016/j.exer.2025.110242","DOIUrl":"10.1016/j.exer.2025.110242","url":null,"abstract":"<div><div>Subretinal injection of gene products is the only treatment option for inherited retinal diseases. However, this procedure induces localized high multiaxial deformations, potentially causing irreversible tissue damage due to retinal overstretching and tearing. Comprehensive characterization of retinal mechanical behavior is essential for performing safe injections. Although uniaxial tensile test has been used in the literature, it has many limitations for retinal characterization. To date, retinal mechanical properties are poorly understood due to the lack of standardized testing protocol. This study aimed to introduce a combined experimental-computational approach using small punch testing and finite element simulations to investigate retina elastic behavior under biaxial deformations. To develop a suitable testing protocol for retinal samples, we evaluated the impact of environmental conditions on retinal elasticity by performing uniaxial tensile tests on porcine retinal strips in air, in a saline bath, and at different temperatures. The results showed that conditions did not significantly affect the elastic modulus. We then developed an easy and reproducible small punch test protocol, allowing to measure for the first time the load-displacement response of the retina under biaxial deformations. Computational simulations enabled the analysis of retinal deformations and the identification of its elastic modulus (5.5 kPa). The outcomes of this study highlight the great potential of the combined approach as a viable alternative to uniaxial tensile test to advance the understanding of retinal biomechanics. This is essential not only for minimizing sight-threatening surgical complications during injections, but also for building predictive in silico models, and developing biomimetic scaffolds.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110242"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002439","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":"Pharmacological depletion of pericytes induces diabetic retinopathy-like abnormal blood vessels in neonatal rat retina","authors":"Kenta Otsuka,&nbsp;Akane Morita,&nbsp;Toshihide Kashihara,&nbsp;Tsutomu Nakahara","doi":"10.1016/j.exer.2025.110243","DOIUrl":"10.1016/j.exer.2025.110243","url":null,"abstract":"<div><div>Diabetic retinopathy is a major ocular complication associated with diabetes mellitus. Pericyte loss is a hallmark of diabetic retinopathy. The platelet-derived growth factor (PDGF)-B-PDGF receptor-β (PDGFRβ) signaling pathway plays an important role in the proliferation and migration of pericytes. Imatinib, an antineoplastic drug primarily used to treat chronic myelogenous leukemia, inhibits the PDGFRβ tyrosine kinase. In this study, we aimed to determine the time-course of pathological changes in the retinal vasculature following pharmacological depletion of pericytes with imatinib. Rats were injected with imatinib once daily for 1, 2, or 4 days starting on postnatal day (P) 4. The distribution of endothelial cells and pericytes in the retina was assessed at P4, P5, P6, P8, and P11. Single and multiple injections of imatinib (100 mg/kg) significantly decreased the pericyte coverage within the retinal capillaries on the day after the completion of each injection protocol. After pericyte coverage decreased, endothelial cell degeneration and microaneurysm formation were initiated. Following the elimination of the inhibitory effect of imatinib on the PDGFRβ signaling pathway, the pericyte coverage returned to control levels but structural abnormalities of the retinal vasculature with microaneurysms and dense capillaries were observed. Vascular pathological features are similar to those of the early clinical manifestations of diabetic retinopathy. Therefore, these rats could serve as animal models to study the mechanisms underlying the pathological changes that occur after pericyte loss in diabetic retinopathy.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110243"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002444","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":"Establishment and evaluation of rabbit model for corneal ectasia by photorefractive keratectomy","authors":"Lin Ye ,&nbsp;Yongjiu Lv ,&nbsp;Chenli Feng ,&nbsp;Jiayue Yuan ,&nbsp;Xueqi Lin ,&nbsp;Qianhong Feng ,&nbsp;Shunmei Ji ,&nbsp;Wei Wu ,&nbsp;Jinhui Dai","doi":"10.1016/j.exer.2025.110248","DOIUrl":"10.1016/j.exer.2025.110248","url":null,"abstract":"<div><div>The study aimed to compare the effects of different types of excimer laser keratectomy on rabbit corneas and to identify the optimal disease model for corneal ectasia. Additionally, investigating the structural and molecular alterations in the novel disease model helped explore the mechanisms underlying biomechanical cues in corneal ectasia. 2.0–2.5 kg New Zealand white rabbits were treated with different types of excimer laser keratectomy, including comparisons between photorefractive keratectomy (PRK) and phototherapeutic keratectomy (PTK) surgeries, as well as comparisons of different ablation depths of PRK. Detailed tests on post-surgery corneas included pentacam analyzer, H&amp;E staining and optical coherence tomography (OCT), transmission electron microscopy (TEM), raman spectroscopy and uniaxial tensile tests. Later, tandem mass tag-labeled proteomics and multiply statistic analysis were performed on post-PRK75 corneas. Western blot was used to validate protein expression. Herein, we found that tapered corneal thinning in post-PRK corneas predisposed to corneal ectasia. Greater ablation depth increased ectasia risk. PRK75 (ablation of 75% of corneal thickness using PRK mode) emerged as the optimal modeling approach, evidenced by significant and sustained corneal ectasia for 4 weeks. The 4-week post-PRK75 corneas were evaluated by changes in stromal cell microstructure, basement membrane, collagen lamellae, collagen covalent bonds and decreased corneal biomechanical strength. Additionally, PRK75 surgery induced 109 differentially expressed proteins (DEPs), with 51 previously linked to human corneal ectasia. The statistic analysis demonstrated the dysregulation of immue response was involved in the post-PRK75 corneas, and identified nine core proteins involved in corneal ectasia, including SERPINH1, ALDH1A1, MMP10, A2M, GSTM3, CD44, CLU, C3, and ITGB2. Therefore, we concluded that PRK75 was a novel and reliable modeling method for corneal ectasia, resemble human corneal ectasia. The intrinsic structural remodeling and molecular alteration in post-PRK75 corneas could shed lights on understanding the mechanism of biomechanical cues in corneal ectasia in the future.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"251 ","pages":"Article 110248"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037713","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":"Topical application of amniotic membrane extract at a clinically correlated dose is effective in limiting complications in an experimental ocular alkaline burn model","authors":"Muhammed Dara Tas ,&nbsp;Mehmet Gurdal ,&nbsp;Meltem Kocamanoglu ,&nbsp;Ilayda Korkmaz ,&nbsp;Mesut Arici ,&nbsp;Banu Yaman ,&nbsp;Melis Palamar ,&nbsp;Nuri Yildirim ,&nbsp;Ali Çalışır ,&nbsp;Eda Seçil Gönen ,&nbsp;Ilgin Timarci Becerik ,&nbsp;Ozlem Barut Selver","doi":"10.1016/j.exer.2025.110259","DOIUrl":"10.1016/j.exer.2025.110259","url":null,"abstract":"<div><div>The purpose of this study is to investigate the clinical and histopathological effectiveness of topical amniotic membrane extract (AME) applied at a clinically relevant dose in an experimental corneal alkaline burn model and to compare the results with amniotic membrane transplantation (AMT) as one of the most frequently used biologically based treatment options. To create an alkaline burn model, NaOH-impregnated filter paper was applied to all rabbits for 30 s. Rabbits were divided into 3 groups: Group 1 (n = 6): AME eye drop; Group 2 (n = 6): AMT; Group 3 (n = 4): control group. AME eye drops were applied as 1 drop 4 times a day for 28 days. Clinical findings including corneal opacity, corneal vascularization, limbal stem cell deficiency (LSCD) was evaluated and graded in accordance with the updated literature. On day 28, corneas were histopathologically examined under the light microscope. Stromal inflammation, stromal fibrosis, intraepithelial edema, and corneal vascularization were scored in each group. When the groups were compared clinically, corneal opacity was significantly (p = 0.009) lower in the AME group. While lower LSCD grades were observed in the AME group, this difference was not significant (p &gt; 0.05). Histopathologically; in the AME group, stromal inflammatory cell inflammation, corneal vascularization, intraepithelial edema, stromal fibrosis, and metaplastic epithelial layer thickness were significantly (p = 0.004; p = 0.022; p = 0.008; p = 0.002; p = 0.002, respectively) lower than the other groups.In this study, it was shown that AME eye drops were clinically and histopathologically more successful in providing corneal healing than the AMT and control groups in the ocular alkaline burn model. These findings are valuable as they show that AME eye drops may be an easy-to-apply biologically based treatment alternative to AMT in chemical burns.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110259"},"PeriodicalIF":3.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074287","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":"Disruption of circadian intraocular pressure fluctuations in mice by the Lyst beige-J mutation","authors":"Colleen M. McDowell ,&nbsp;Laura M. Dutca ,&nbsp;Stewart Thompson ,&nbsp;Megan Riker ,&nbsp;Adam Hedberg-Buenz ,&nbsp;Kacie J. Meyer ,&nbsp;Michael G. Anderson","doi":"10.1016/j.exer.2025.110266","DOIUrl":"10.1016/j.exer.2025.110266","url":null,"abstract":"<div><div>Intraocular pressure (IOP) follows a circadian rhythm. In both humans and mice, IOP is normally slightly elevated at night during the dark phase of the light cycle. In studying a strain of mice for possible indices of glaucoma, we incidentally discovered that C57BL/6J mice homozygous for the <em>beige-J</em> mutation of the <em>Lyst</em> gene lack a circadian fluctuation in IOP. Instead of having an elevated dark phase IOP, homozygotes exhibit a uniform IOP characteristic for light period values of C57BL/6J mice. The <em>beige-J</em> mutation results from deletion of a single isoleucine amino acid in the LYST WD40 motif likely to influence protein-protein interactions. Based on the literature, we hypothesized that CSNK2B (casein kinase 2, beta polypeptide) might be a relevant interacting protein, which we confirmed with a pulldown assay as a binding partner of wild-type, but not <em>beige-J</em> encoding, LYST protein. Treating wild-type mice with 4,5,6,7-tetrabromobenzotriazole (TBB), a casein kinase 2 inhibitor, recapitulated the <em>beige-J</em> mutant phenotype in preventing a rise in IOP during the dark period. Together, these results identify <em>Lyst beige-J</em> mice as a new strain for studying circadian IOP regulation and point to casein kinase 2 as a key molecule of interest.</div></div>","PeriodicalId":12177,"journal":{"name":"Experimental eye research","volume":"252 ","pages":"Article 110266"},"PeriodicalIF":3.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079170","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}