Molecular Vision最新文献

{"title":"A mutation in <i>Bicdl1</i> (BICD family-like cargo adaptor 1) leads to mild outer retina thinning and late retinal dysfunction in a mouse model.","authors":"Gizem Ulker-Yilmazer, Dogan Can Kirman, Tian Yu, Emily R Turpin, Sangita Shrestha, Seher Yuksel, Yu-Guang He, Sara Ludwig, Ashwani Kumar, Chao Xing, Eva M Y Moresco, Bruce A Beutler, Bogale Aredo, Rafael L Ufret-Vincenty","doi":"10.63500/mv_v32_281","DOIUrl":"10.63500/mv_v32_281","url":null,"abstract":"<p><strong>Purpose: </strong>Both photoreceptors and the retinal pigment epithelium (RPE) are highly metabolically active cell types that require extensive molecular transport and adequate energy production to maintain their function. We tested the hypothesis that cargo adaptor protein Bicdl1 has a non-redundant role in retinal health.</p><p><strong>Methods: </strong>Using an unbiased forward genetics approach, we identified an association between outer retinal thinning and a point mutation in <i>Bicdl1</i>. We generated <i>Bicdl1</i> KI (knock-in) mice carrying the same point mutation identified in the mutagenesis pipeline and characterized the resulting retinal phenotype using optical coherence tomography (OCT), fundus photography, histology, immunofluorescence, electroretinography, electron microscopy (EM), and transcriptomics.</p><p><strong>Results: </strong>Analysis of OCT images and histology sections demonstrated a mild decrease in outer retinal thickness and rod outer segment thickness. We found an increased number of fundus spots in retinal photographs and an increased number of Iba1⁺/Tmem119⁺ cells on RPE flat mounts of <i>Bicdl1</i> KI mice. Electroretinography in aging mice showed a mild impairment in visual function, reflected by a reduction in a-wave amplitudes. EM revealed fewer RPE mitochondria in <i>Bicdl1</i> KI mice. To elucidate the mechanistic basis of the observed retinal degeneration, transcriptomic studies were conducted, which suggested an association between low <i>Bicdl1</i> expression and increased oxidative phosphorylation in photoreceptors.</p><p><strong>Conclusion: </strong>Despite the expression of many cargo adaptor proteins and dynein activators in the retina, we identified a novel non-redundant role of <i>Bicdl1</i> in retinal homeostasis. Pathway analysis of transcriptomic data suggested that <i>Bicdl1</i> deficiency may affect energy metabolism.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"281-306"},"PeriodicalIF":1.8,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13568186/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SS31 protects damaged retinal cells through the AMPK/DRP1 signaling pathway.","authors":"Na Cui, Rui-Xue Zhang, Qian Yang, Yuan Ren, Jun Jia, Xia Wang, Xu Liu, Yuan He","doi":"10.63500/mv_v32_265","DOIUrl":"10.63500/mv_v32_265","url":null,"abstract":"<p><strong>Purpose: </strong>Glaucoma is a group of neurodegenerative diseases characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Mitochondrial dynamics contribute to the maintenance of neuronal homeostasis, and abnormalities can lead to the development of glaucoma. SS31 is a mitochondria-targeting short peptide that has been found to protect mitochondrial function and thereby protect damaged retina-associated cells. The aim of this study is to investigate whether SS31 protects damaged retinal cells by activating the AMPK/DRP1 pathway.</p><p><strong>Methods: </strong>The relationship between SS31 and oxidative stress was determined by live-cell imaging. The cells were inoculated in the well plate and treated with H₂O₂ (150 μM) for 24 h and pretreated with or without SS31 (100 nM), AICAR (17.5 μM), or dorsomorphin (7 μM) for 2 h. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) were used to evaluate cell viability. Mitochondrial genetic stability was detected by droplet digital PCR. The expression of AMPK and DRP1 was detected by western blot. In addition, intraocular pressure and retinal thickness were evaluated in mice with acute ocular hypertension.</p><p><strong>Results: </strong>SS31 inhibited H₂O₂-induced cell death of 661W through the AMPK signaling pathway and maintained mitochondrial genetic stability. SS31 regulates AMPK/Drp1 signaling in 661W cells after oxidative stress. SS31 reduced intraocular pressure and maintained normal retinal thickness in mice with acute ocular hypertension.</p><p><strong>Conclusions: </strong>SS31 regulates mitochondrial dynamic network remodeling by activating AMPK/DRP1 signaling pathway and protects retinal-related cells.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"265-279"},"PeriodicalIF":1.8,"publicationDate":"2026-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13568172/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reporter-guided photoreceptor differentiation in 2D culture using PGP1-hIPSCs: A comparable alternative to 3D organoid systems?","authors":"Davinia Beaver, Adrian C Cioanca, Nigel L Barnett","doi":"10.63500/mv_v32_232","DOIUrl":"10.63500/mv_v32_232","url":null,"abstract":"<p><strong>Purpose: </strong>To develop and characterize a xeno-free, two-dimensional (2D) differentiation protocol for directing human induced pluripotent stem cells (hIPSCs) toward photoreceptor (PhR)-like cells, using a live-reporter system and transcriptomic analysis to evaluate lineage fidelity and maturation compared to the three-dimensional (3D) culture paradigm.</p><p><strong>Methods: </strong>A CRISPR/Cas9-engineered PGP1 hIPSC line expressing fluorescent reporters for retinal markers (<i>VSX2</i>, <i>BRN3B</i>, and <i>RCVRN</i>) was differentiated in adherent culture using chemically defined media supplemented with small molecules (T3, DAPT, taurine, and retinoic acid). Differentiation was assessed over time by immunocytochemistry, flow cytometry, reverse transcription quantitative polymerase chain reaction, ultrastructural imaging (transmission electron microscopy and scanning electron microscopy), and bulk RNA sequencing. Comparative transcriptomic analysis with 3D retinal organoid data was conducted to evaluate developmental kinetics and pathway enrichment.</p><p><strong>Results: </strong>The 2D protocol reproducibly generated PhR-like cells expressing PhR-associated protein markers, including CRX, NR2F2, RCVRN, THRβ OPSIN-S, OPSN-M/L, and ARR3. Flow cytometric analysis demonstrated 93.6%, 96.2%, and 70.3% of RCVRN, OPSN-M/L, and OPSN-S positive populations at day (D) 42, while up to 97.4% of cells stained positive for RCVRN by D52. Early commitment to a PhR lineage was evident by D30, supported by transcriptional profiles consistent with PhR-like ontogeny. Ultrastructural analyses revealed features of putative inner and outer segments, including developing cilia and disc-like \"whorls\" supported by expression of gap junction protein markers and cilium markers (TMEM138 and CX36). Bulk RNA sequencing demonstrated faithful temporal regulation of PhR gene networks and highlighted accelerated differentiation compared to 3D cultures.</p><p><strong>Conclusions: </strong>This pilot xeno-free 2D differentiation protocol offers a timely and scalable method for generating PhR-like cells from hIPSCs comparable to standard 3D culture systems. The results validate its downstream utility for retinal cell therapy development, high-throughput screening, and transplantation outputs pending further investigation, while supporting the transcriptome dominance model as a framework for evaluating photoreceptor fate acquisition in this culture paradigm.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"232-253"},"PeriodicalIF":1.8,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-inflammatory action of fluvoxamine in an endotoxin-induced uveitis rat model: Histopathological evidence.","authors":"Gülşah Usta Sofu, Halil Aşcı, Şerife Taşan, Dilek Özkaya, Simge Garlı","doi":"10.63500/mv_v32_255","DOIUrl":"10.63500/mv_v32_255","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the potential protective effects of fluvoxamine (FVX), a selective serotonin reuptake inhibitor with known anti-inflammatory properties, on corneal, limbal, and retinal tissues in a rat model of endotoxin-induced uveitis (EIU), clinical and histopathologic evaluations were performed.</p><p><strong>Methods: </strong>Twenty-eight female Wistar Albino rats were divided into four groups: controls, EIU, EIU + FVX, and FVX (n = 7 per group). EIU was induced by a single intraperitoneal injection of lipopolysaccharide (LPS). FVX or normal saline (NS) was administered 30 min before LPS or NS injection. Clinical ocular inflammation was assessed using slit-lamp biomicroscopy 6 h postinjection. Following euthanasia, enucleated eyes were processed for histopathologic analysis of corneal, limbal, and retinal tissues.</p><p><strong>Results: </strong>Total corneal and epithelial thickness were measured, while limbal and retinal lesions were semiquantitatively graded. The EIU group exhibited significantly increased clinical ocular inflammation scores compared to the control, EIU + FVX, and FVX groups (<i>p</i> < 0.0001 for all). At the microscopical analysis, the EIU group showed significant corneal epithelial thickening, cellular changes, edema, hemorrhage, and increased total corneal thickness compared to the control group (<i>p</i> < 0.001). In addition, histopathologic analysis revealed retinal hyperemia and edema in the EIU group but not in the EIU + FVX, FVX, or control groups. Histopathologic scores confirmed significant retinal changes in the EIU group compared to the others (<i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>FVX significantly reduced clinical signs of ocular inflammation and mitigated histopathologic damage in the cornea, limbus, and retina.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"255-263"},"PeriodicalIF":1.8,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13568192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing mitochondrial phenotypes in a cybrid model of dry age-related macular degeneration.","authors":"Jacob Dohl, Nyan Lin Zaw, Jett Nguyen, Gordon Burns, Brandon Park, Shari Atilano, Kevin Schneider, Marilyn Chwa, Maria Cristina Kenney","doi":"10.63500/mv_v32_196","DOIUrl":"10.63500/mv_v32_196","url":null,"abstract":"<p><strong>Purpose: </strong>Dry age-related macular degeneration (DAMD) is the leading cause of vision loss in developed countries, yet there are no FDA-approved treatments currently available. Mitochondria play a significant role in the pathology of DAMD; the retinal pigment epithelium cells of patients with DAMD exhibit mitochondrial dysfunction, elevated levels of mitochondrial DNA lesions, and increased mitochondrial reactive oxygen species. Investigations into the mitochondrial contributions to DAMD are complex as human tissue is challenging to acquire, and animal models do not fully recapitulate disease phenotypes. Cytoplasmic hybrid (cybrid) cells, formed by depleting the mitochondria of an immortalized cell line and fusing with patient platelets, are a possible model for mitochondrial studies on DAMD. This study evaluates if cybrid models of DAMD recapitulate the mitochondrial hallmarks of the disease, including mitochondrial dysfunction, decreased mitochondrial protein levels, lipid accumulation, and mitochondrial DNA lesions.</p><p><strong>Methods: </strong>The mitochondrial functions of five healthy and five DAMD cybrid cell lines were compared based on mitochondrial oxygen consumption rates, membrane potential, and protein expression. Secondary factors of mitochondrial dysfunction, including lipid accumulation and mitochondrial DNA stress response, were also examined.</p><p><strong>Results: </strong>Compared to healthy control cybrid lines, we found no alterations in bioenergetics, protein levels, and lipid accumulation in DAMD cybrid lines. Mitochondrial DNA stress responses were aberrant in DAMD cybrids compared to healthy controls, suggesting some conserved mitochondrial dysfunction.</p><p><strong>Conclusions: </strong>Taken together, this study suggests that these DAMD cybrids do not fully recapitulate DAMD mitochondrial pathology, though this is limited to the study population of males with the H mtDNA haplogroup. However, there may be a niche for cybrid cell lines in investigating mitochondrial DNA phenotypes in patients with DAMD. This is likely because DAMD is a multifactorial disease, dependent upon an individual's genetics and the retinal microenvironment.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"196-208"},"PeriodicalIF":1.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-like receptor 9 in retinal pigment epithelial cells: Expression, function and the role of TGF-β1.","authors":"Elisabeth Esser, Heidrun Kuhrt, Focke Ziemssen, Margrit Hollborn","doi":"10.63500/mv_v32_210","DOIUrl":"10.63500/mv_v32_210","url":null,"abstract":"<p><strong>Purpose: </strong>Inflammatory processes in the aged retina may be exacerbated by systemic infection with viruses and bacteria, potentially aggravating age-related macular degeneration (AMD). Toll-like receptors (TLR) are key mediators in detecting pathogen-associated molecular patterns (PAMPs) and host-derived damage-associated molecular patterns (DAMPs). This study aimed to investigate <i>TLR</i> gene expression in cultured retinal pigment epithelial (RPE) cells, focusing particularly on TLR9.</p><p><strong>Methods: </strong>TLR gene expression was assessed using semiquantitative qPCR, while protein expression was evaluated through western blotting, immunocytochemistry, and ELISA. Hypoxic conditions were simulated using CoCl₂ or by incubation in a 0.1% O₂ atmosphere. RPE cell proliferation and viability were examined using bromodeoxyuridine (BrdU) and MTT assays. Cell necrosis and apoptosis were analyzed with a cellular DNA fragmentation ELISA.</p><p><strong>Results: </strong>Among the <i>TLRs</i> analyzed, <i>TLR9</i> showed the most pronounced upregulation under hypoxic conditions. TLR9 protein expression was similarly induced by CoCl₂ as well as in a 0.1% O₂ atmosphere. Hypoxia increased the protein levels of γH2A.X, a marker for DNA damage and cellular senescence. The TLR9 agonist ODN 1826 induced the gene expression of downstream signaling molecules (<i>MYD88</i>, <i>IRF7, RELA</i>), inflammatory factors (<i>IFNA, COX2</i>), and <i>MMP9</i> as well as the secretion of TGF-β1. These effects were reversed by TLR9 inhibitors (ODN 2088 and ODN INH-18). Transforming growth factor (TGF)-β1 significantly suppressed the TLR9 expression at both the mRNA and protein levels. This suppressive effect was reversed at the RNA level by inhibiting components of the TGF-β1 signaling pathway, including activin receptor-like kinase (ALK), Smad3, p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphatidylinositol 3-kinase (PI3K) under hypoxic conditions.</p><p><strong>Conclusions: </strong>TLR9 activation under hypoxic conditions initiates pro-inflammatory pathways in RPE cells. In the aging retina, viral and bacterial infections and/or DAMPs may further amplify these responses, worsening retinal degeneration. TGF-β1 may exert protective, anti-inflammatory effects by downregulating TLR9 expression.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"210-230"},"PeriodicalIF":1.8,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13585427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of corneal epithelial thickness parameters with different degrees of keratoconus in the diagnosis of keratoconus.","authors":"Tao Wang, Qixin Cao","doi":"10.63500/mv_v32_143","DOIUrl":"10.63500/mv_v32_143","url":null,"abstract":"<p><strong>Purpose: </strong>To assess the diagnostic value of corneal epithelial thickness parameters measured by RTVue XR OCT in different stages of keratoconus.</p><p><strong>Methods: </strong>This is a cross-sectional study of 64 patients (64 eyes) with keratoconus who visited from January 2021 to December 2023. The control group randomly had 46 patients (46 eyes) with refractive errors. The RTVue XR OCT was used to measure the distribution and parameter indicators of corneal epithelial thickness in various regions of the normal corneal group. We measured parameters with statistically significant differences and calculated cutoff points, sensitivity, specificity, the area under the receiver operating characteristic curve, and the Youden index for the parameter indicators in the preclinical, mild, moderate, and severe keratoconus groups during the clinical period and in the normal control group.</p><p><strong>Results: </strong>The normal corneal epithelial thickness was unevenly distributed in various regions within the range of 0 to 5 mm. The cornea was thinner above and below the nose, as well as thicker above and below the temporal area, and the central area of the cornea was the thinnest. The Min-Max parameter showed the highest diagnostic value for preclinical keratoconus. For mild, moderate, and severe keratoconus, parameters including superior-inferior (S-I), supranasal (SN)-infranasal (IT), Max, and standard deviation showed high diagnostic value. SN-IT and standard deviation demonstrated high specificity and sensitivity in distinguishing the clinical keratoconus groups from the normal control group.</p><p><strong>Conclusions: </strong>Corneal epithelial thickness parameters are valuable for diagnosing various stages of keratoconus. The Min-Max parameter is particularly valuable for preclinical diagnosis, while SN-IT and standard deviation are highly valuable for diagnosing clinical stages.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"143-153"},"PeriodicalIF":1.8,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13518047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinal ribbon synapses and the potential functional role of TIAM1: A structural and molecular perspective.","authors":"Martha Emil Adly","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Purpose: Retinal and inner ear ribbon synapses are specialized sensory synapses characterized by synaptic ribbons, electron-dense and protein-rich structures that enable rapid and sustained neurotransmitter release. This review aims to examine the molecular architecture of ribbon synapses with a particular focus on the potential involvement of Tiam1, a guanine nucleotide exchange factor implicated in neuronal development and synaptic plasticity.</p><p><strong>Methods: </strong>A comprehensive review of the available literature was conducted to summarize current knowledge on the structural organization and molecular components of ribbon synapses. Particular attention was given to studies investigating Tiam1 expression, function, and its possible role in cytoskeletal remodeling and synaptic regulation.</p><p><strong>Results: </strong>Evidence supports the central role of RIBEYE as the primary structural component of ribbon synapses; however, the regulatory mechanisms governing ribbon formation and function remain incompletely understood. Recent studies suggest a potential contribution of Tiam1 in modulating synaptic organization and function through Rac1 activation and cytoskeletal regulation, although direct experimental evidence in ribbon synapses is still limited.</p><p><strong>Conclusions: </strong>Ribbon synapses are critical for sustained neurotransmission in sensory systems, yet their molecular regulation remains incompletely defined. Tiam1 emerges as a promising candidate molecule that may influence ribbon synapse function. Future experimental studies are needed to clarify its localization, molecular interactions, and contribution to synaptic organization and plasticity.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"131-141"},"PeriodicalIF":1.8,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070731/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of retinal ganglion cell subtypes across six different inbred mouse strains.","authors":"Su-Ting Lin, Fangyu Lin, Jiaxing Wang, Eldon E Geisert","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Retinal ganglion cells (RGCs) are the principal conduits responsible for propagating visual stimuli from the retina to visual centers in the brain. The loss of RGCs leads to visual deficits following trauma or in diseases such as glaucoma. Mouse models are consistently used to investigate root causes for RGC loss. This study quantifies the total number of RGCs and selected RGC subtypes across six strains of inbred mice used in ophthalmic research.</p><p><strong>Methods: </strong>Six mouse strains (C57BL/6J, BALB/cByJ, 129X1/SvJ, A/J, CBA/CaJ, and CAST/EiJ) were selected to represent genetic diversity across the mouse genome. Normal retinas were immunostained for POU6F2, BRN3A, SATB2, OPN4, SMI32, and TO-PRO-3. Cells positively labeled for POU6F2, BRN3A, and SATB2 were quantified using an automated deep learning tool, RGCode. Cells labeled with OPN4, SMI32, and TO-PRO-3 were quantified using the Fiji software.</p><p><strong>Results: </strong>We found statistically significant differences in the quantity (Mean±SEM) and percentage of different RGCs across the inbred mouse strains. The total number of RGCs per retina ranged from 39,961±838 in CAST/EiJ to 53,872±1864 in 129X1/SvJ (p<0.005). Global BRN3A counts ranged from 34,572±494 in CAST/EiJ to 44,253±798 in C57BL/6J (p<0.005). SATB2 counts ranged from 9944±384 in BALB/cByJ to 15,872±1196 in CBA/CaJ (p<0.005). OPN4 density ranged from 110±7 cells/mm² in CAST/EiJ to 164±13 cells/mm² in 129X1/SvJ (p<0.05). Differences in SMI32 density were not significant across all strains, with densities ranging from 183±14 cells/mm² in A/J to 279±12 cells/mm² in C57BL/6J (not significant).</p><p><strong>Conclusions: </strong>There is a significant variation in total RGC counts and RGC subtypes across the different mouse strains. When working with different strains of mice, it is important to consider this strain-based variation before drawing conclusions from experimental data.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"120-129"},"PeriodicalIF":1.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA interference to reduce <i>Egr1</i> expression in rods delays retinal degeneration in a model of retinitis pigmentosa.","authors":"Luca Merolla, Antonia Fottner, Cornelia Imsand, Claudia Matter, Jessica Rowlan, Maureen Neitz, Larissa P Govers, Marijana Samardzija, Christian Grimm","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Purpose: </strong>Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases characterized by progressive photoreceptor degeneration. The early growth response-1 gene (<i>Egr1</i>) is an immediate-early gene implicated in neurodegenerative and stress responses in the retina, among many other tissues. While its expression is induced in the retina across various RP models, its functional role in the degenerative process remains unclear. This study aimed to investigate the contribution of <i>Egr1</i> to photoreceptor degeneration in vivo.</p><p><strong>Methods: </strong>We used adeno-associated virus (AAV)-mediated RNA interference and transgenic overexpression to modify <i>Egr1</i> levels in rod and cone photoreceptors of wild-type and <i>Rho^P23H/+</i> mice. Rod- and cone-specific promoters enabled cell-specific expression. Exposure to high levels of white light was used to induce retinal degeneration in wild-type mice. We assessed retinal structure and transgene expression through funduscopy, optical coherence tomography (OCT), immunofluorescence, and histological analysis. We measured <i>Egr1</i> mRNA expression levels via real-time PCR and assessed the effects of <i>Egr1</i> modulation on the retina by determining the thickness of the outer nuclear layer (ONL) and the number of surviving cones.</p><p><strong>Results: </strong>Similar to other models of retinal degeneration, <i>Egr1</i> was induced in the retina after light exposure and in the <i>Rho^P23H/+</i> mouse during degeneration. AAV-mediated down- or upregulation of <i>Egr1</i> in rods or cones did not affect retinal morphology in wild-type mice. In <i>Rho^P23H/+</i> mice, <i>Egr1</i> knockdown in rods modestly preserved ONL thickness up to 12 weeks after AAV injection. Overexpression did not accelerate degeneration beyond controls. <i>Egr1</i> modulation in cones of wild-type or <i>Rho^P23H/+</i> mice did not affect cone survival.</p><p><strong>Conclusions: </strong><i>Egr1</i> upregulation is a consistent early marker of photoreceptor stress, independent of the nature of the underlying stimulus. Since moderate support for cell survival and preservation of retinal morphology was achieved through the downregulation of <i>Egr1</i> expression in rods, but not in cones of the <i>Rho^P23H/+</i> mouse, the function of EGR1 in degenerative processes may be cell type specific. Although <i>Egr1</i> may contribute to disease progression, it is unlikely to be a causative factor for degeneration. Our findings underscore the complexity of the transcriptional response in retinal degeneration and suggest that <i>Egr1</i> is a secondary effector of degenerative processes in rods.</p>","PeriodicalId":18866,"journal":{"name":"Molecular Vision","volume":"32 ","pages":"102-118"},"PeriodicalIF":1.8,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}