Investigative ophthalmology & visual science最新文献

{"title":"Author Response: Unveiling Statins and Genetics in Age-Related Macular Degeneration Progression: What Is the Appropriate Modeling Strategy?","authors":"Patricia Barreto, Claudia Farinha, Rita Coimbra, Rufino Silva","doi":"10.1167/iovs.66.3.3","DOIUrl":"10.1167/iovs.66.3.3","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"3"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541374","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":"Epigenetic ALYREF/UHRF1/RHOB Axis in Corneal Wound Healing and Implications for Epithelial Tumorigenesis.","authors":"Hua Zhang, Shuning Lan, Disuo Ren, Xiaoyan Chen, Yong Lin, Qiongjie Cao, Weiwei Xu, Jiao Wang, Peter Sol Reinach, Dongsheng Yan, Guangying Luo","doi":"10.1167/iovs.66.3.54","DOIUrl":"10.1167/iovs.66.3.54","url":null,"abstract":"<p><strong>Purpose: </strong>Corneal epithelial wound healing (CEWH) is a complex process influenced by epigenetic regulation. Ubiquitin-like with plant homeodomain (PHD) and ring finger domains 1 (UHRF1), it plays a key role in integrating epigenetic signals. However, its precise function in modulating CEWH remains poorly understood. We describe here the functional mechanisms of UHRF1 in modulating CEWH.</p><p><strong>Methods: </strong>Quantitative Reverse Transcription PCR (RT-qPCR), immunofluorescence, and gene manipulation were used to investigate UHRF1 expression patterns and functions during CEWH. Integrated multi-omics and targeted bisulfite sequencing (TBS) were performed to reveal the downstream target of UHRF1. Mutation assay was used to examine whether Aly/REF export factor (ALYREF) can recognize and bind RNA m5C-UHRF1. Gene expression profiling interactive analysis (GEPIA) was utilized to validate the correlation of UHRF1 with its upstream and downstream targets.</p><p><strong>Results: </strong>In this study, we demonstrate that UHRF1 enhances CEWH and sustains DNA methylation during CEWH, which is essential for this effect. A multi-omics analysis identified Ras homolog family member B (RHOB) as a downstream target of UHRF1. Our findings further revealed that UHRF1 epigenetically downregulates RHOB, thereby facilitating CEWH. Moreover, we showed that ALYREF binds to m5C sites on UHRF1 mRNA and enhances its translation. Finally, our analysis of molecular alterations and the clinical significance of ALYREF, UHRF1, and RHOB expression suggests that this epigenetic axis is also relevant in epithelial-derived tumors, which represent approximately 90% of all tumors.</p><p><strong>Conclusions: </strong>Our study identifies a novel epigenetic ALYREF/UHRF1/RHOB axis that enhances CEWH. Importantly, this axis appears to be conserved across various epithelial-derived tumors, suggesting its broader biological significance.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"54"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11951065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700300","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":"Topographic Analysis of Two-Wavelength Autofluorescence Supports Higher Macular Xanthophyll Pigment in AMD Than Aging: ALSTAR2 Baseline.","authors":"Lukas Goerdt, Andreas Berlin, Liyan Gao, Thomas A Swain, Sarah S Kim, Gerald McGwin, Mark E Clark, Deepayan Kar, Cynthia Owsley, Kenneth R Sloan, Christine A Curcio","doi":"10.1167/iovs.66.3.61","DOIUrl":"10.1167/iovs.66.3.61","url":null,"abstract":"<p><strong>Purpose: </strong>To advance metabolic imaging of the high-risk macula lutea by quantifying the topography of macular pigment optical density (MPOD), measured with two-wavelength autofluorescence (2WAF), and quantitative (short-wavelength) autofluorescence (qAF) intensity, which share the same signal source and cross-retinal light path, in aging, early (e), and intermediate (i) age-related macular degeneration (AMD).</p><p><strong>Methods: </strong>2WAF and qAF images of 384 pseudophakic eyes of 230 persons (mean age, 74.2 ± 5.7 years; 145 female) from ALSTAR2 (AREDS 9-step classification: 170, normal; 118, eAMD; 96 iAMD) were shown as maps (intensity, z-score) and meridian plots. Correlations were determined in Early Treatment Diabetic Retinopathy Study (ETDRS) subfields.</p><p><strong>Results: </strong>MPOD was higher in the central subfield (P < 0.01) in iAMD compared to eAMD and normal eyes, and qAF was lower in the central subfield and inner ring (both P < 0.01) in AMD compared to normal eyes. MPOD differed along horizontal versus vertical meridians, depending on disease stage. Pixel-level z-score maps and meridian plots showed distinct annuli of alternating levels of MPOD anchored on the foveal center, unrelated to qAF. Across the central subfield, high 2WAF was associated with low qAF in all disease stages (r = -0.47, r = -0.47, r = -0.42; all P < 0.001). In the inner ring, correlations were significant for normal and eAMD only (r = -0.31, P = 0.004 and r = -0.22, P ≤ 0.001, respectively).</p><p><strong>Conclusions: </strong>New analytics support previously reported higher MPOD in AMD compared to normal eyes, especially central subfield and inner ring. MPOD and qAF differ by disease-stage-related topography and correlations, supporting independent use in metabolic imaging of the macula lutea.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"61"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11956744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752776","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":"One-Month-Old Rabbits Exhibit a Longer Postoperative Remodeling in Extraocular Muscles Compared to 3-Month-Old Rabbits.","authors":"Jiangtao Lou, Hailu Huang, Yiyi Peng, Chunxiao Wang, Meiping Xu, Xinping Yu","doi":"10.1167/iovs.66.3.12","DOIUrl":"10.1167/iovs.66.3.12","url":null,"abstract":"<p><strong>Purpose: </strong>To explore whether there is a difference in postoperative extraocular muscle (EOM) remodeling between 1-month-old and 3-month-old rabbits.</p><p><strong>Methods: </strong>Recession (n = 16) and resection (n = 16) were performed on the right superior rectus (SR) muscles of 1-month-old and 3-month-old rabbits. SR tissues were harvested 1 and 4 weeks post-surgery (n = 4 for each group), and mid-belly sections were used to assess myosin heavy chain (MyHC) isoform expression (fast 2X, embryonic, and neonatal MyHCs), activated satellite cells (SCs), and centrally nucleated myofibers. Age-matched unoperated rabbits (n = 4) served as controls.</p><p><strong>Results: </strong>In 1-month-old rabbits, fast 2X-MyHC expression continuously decreased post-recession (all P < 0.01), and embryonic MyHC expression increased both post-recession and post-resection (all P < 0.01), except in the global layer (GL) post-resection. In 3-month-old rabbits, fast 2X-MyHC decreased at 1 week post-recession (in both layers P < 0.01) but returned to preoperative levels by 4 weeks (in both layers P = 1). Embryonic MyHC remained stable (P = 0.239) or increased (in the GL post-recession and in the orbital layer (OL) post-resection, both P < 0.001) at 1 week postoperatively, except in the GL post-resection. It had returned (in the GL post-recession, P = 0.952; in the GL post-resection, P = 0.574) or nearly returned (in the OL post-resection, P = 0.038) to preoperative levels in both layers by 4 weeks. Activated SCs in 1-month-old rabbits continuously increased post-surgery (all P < 0.05), except in the OL post-resection. In 3-month-old rabbits, SCs remained stable at 1 week but decreased by 4 weeks post-surgery (all P < 0.01), except in the OL post-resection. Centrally nucleated myofibers were more prevalent in 1-month-old rabbits by 4 weeks postoperatively.</p><p><strong>Conclusions: </strong>One-month-old rabbits displayed longer postoperative remodeling and greater plasticity in EOMs than 3-month-old rabbits. The difference in postoperative remodeling may impact strabismus surgery outcomes in patients of different developmental stages.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"12"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556676","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":"Isolated Mitochondrial Transplantation as a Novel Treatment for Corneal Chemical Burns.","authors":"Dan Jiang, Jinjie Yu, Xiaoqing Wu, Xintong Yu, Pinyan Jin, Huikang Zheng, Huiru Liu, Wei Xu, Qizhou Lian, Wei Chen","doi":"10.1167/iovs.66.3.14","DOIUrl":"10.1167/iovs.66.3.14","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate the therapeutic potential of isolated mitochondrial transplantation for the restoration of corneal surface injury in mice after corneal chemical burn.</p><p><strong>Methods: </strong>Mitochondria were isolated from mesenchymal stem cells via ultracentrifugation, followed by an assessment of their purity and viability. The internalization of mitochondria by human corneal epithelial cells was tracked using a live fluorescence imaging system. Apoptosis-related markers and mitochondrial function were measured by Western blotting and flow cytometry, respectively. Mitochondrial morphology was examined using confocal laser scanning microscopy. The therapeutic effects of subconjunctival administration of isolated mitochondria in vivo were evaluated by fluorescein sodium staining and histopathological examination of the corneas.</p><p><strong>Results: </strong>Our study demonstrates that corneal epithelial cells possess the capacity to internalize isolated exogenous mitochondria in vitro. Under oxidative stress conditions, recipient cells exhibited an enhanced uptake of exogenous mitochondria. We observed a decrease in apoptosis and a reduction in oxidative stress levels within the recipient cells, as well as a partial restoration of mitochondrial function. Notably, after a single subconjunctival injection, corneal epithelial cells were able to use isolated mitochondria to enhance the repair process in a mouse model of corneal acid burn.</p><p><strong>Conclusions: </strong>Subconjunctival injection of isolated mitochondria promoted the repair of acute corneal burns in mice. The results of our investigation using injection of isolated mitochondria as a treatment modality for corneal chemical burn offers a novel approach to the treatment of ocular disorders associated with mitochondrial dysfunction.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"14"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567039","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":"Magnetic Resonance Dacryocystography for Precise Diagnosis of Lacrimal and Perilacrimal Lesions.","authors":"Xuejun Guo, Min Gao, Yulong Qi, Qiao Shi, Qiqiang Li, Mingmei Li, Hongbing Li","doi":"10.1167/iovs.66.3.17","DOIUrl":"10.1167/iovs.66.3.17","url":null,"abstract":"<p><strong>Purpose: </strong>The accurate determination of the etiology and location of lacrimal passage obstruction is key to treatment. However, the main assessments for lacrimal passage are invasive and have limited value. This study aimed to analyze the causes of obstruction of the lacrimal passage and investigate the diagnostic value of magnetic resonance dacryocystography (MRD).</p><p><strong>Methods: </strong>Fifty-six patients (69 eyes) with lacrimal disease underwent MRD after lacrimal irrigation. The stenotic site and degree were determined. The accuracies of the diagnoses of lesions at different sites based on MRD and routine clinical assessment were determined and compared, and a noninferiority test was used to verify the values obtained via MRD.</p><p><strong>Results: </strong>The lesion location determined through lacrimal irrigation was inconsistent with that determined through MRD. The overall accuracy of routine clinical assessment was approximately 79.7% (55 of 69) and that of MRD reached 98.6% (68 of 69). For the lesion location, the clinical misdiagnosis rates were 38.9%, 43.8%, and 63.6% for the lacrimal sac, nasolacrimal duct, and perilacrimal passage, respectively. The MRD and surgical pathology results for the lacrimal sac, nasolacrimal duct, and perilacrimal passage were consistent, except for the lacrimal canaliculus. The P value for the noninferiority of MRD to surgical pathology was 0.32.</p><p><strong>Conclusions: </strong>MRD is noninvasive and has high value for determining the cause, location, and degree of lacrimal stenosis. Its findings are nearly as accurate as those of surgical pathology. MRD should be recommended over other invasive methods for evaluating lacrimal and prelacrimal lesions.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"17"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567046","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":"LncRNA ENST00000581911 Regulates Extraocular Muscle Remodeling by Interacting With KHSRP in Thyroid Eye Disease.","authors":"Mingsu Shi, Rongmei Zhou, Weiai Shen, Yu Liang, Yihan Zhang, Lingyun Liu, Runyi Shao, Yanxi Fang, Chen Zhao, Lianqun Wu","doi":"10.1167/iovs.66.3.46","DOIUrl":"10.1167/iovs.66.3.46","url":null,"abstract":"<p><strong>Purpose: </strong>Thyroid eye disease (TED) is a visually debilitating and cosmetically disfiguring orbital disorder, characterized by the remodeling of extraocular muscles (EOMs). This study aimed to investigate the role of long non-coding RNA (lncRNA) ENST00000581911 in the EOMs of TED.</p><p><strong>Methods: </strong>LncRNA microarray analysis was performed on EOM tissues sampled from patients with TED and patients with concomitant esotropia. LncRNA ENST00000581911 was identified and subjected to bioinformatics analysis. High-throughput RNA sequencing, CCK-8 assay, CFSE staining, and ELISA were used to investigate the regulatory function of ENST00000581911 in vitro. Furthermore, RNA pull-down, liquid chromatography-tandem mass spectrometry (LC-MS/MS), and western blot (WB) analyses were applied to identify the RNA-binding protein (RBP) interacting with ENST00000581911.</p><p><strong>Results: </strong>A total of 1261 lncRNAs were found to be differentially expressed in the EOMs of TED, with 648 upregulated and 613 downregulated lncRNAs. Among these, the upregulated lncRNA ENST00000581911 exhibited the highest expression level, as validated by quantitative real-time PCR (qRT-PCR). Functional analysis demonstrated that ENST00000581911 might be involved in inflammatory response, regulation of muscle contraction, and amino sugar and nucleotide sugar metabolism. RNA sequencing of ENST00000581911-overexpressing and control orbital fibroblasts (OFs) showed that ENST00000581911 might play a regulatory role in DNA replication, extracellular matrix, and cell cycle. Furthermore, KHSRP was identified as the RBP of ENST00000581911. Overexpression of ENST00000581911 promoted cell proliferation and hyaluronic acid secretion in OFs, whereas silencing KHSRP attenuated these effects.</p><p><strong>Conclusions: </strong>This study provides novel insights into the role of lncRNA ENST00000581911 in the pathogenesis of EOM remodeling in TED. ENST00000581911 may serve as a potential therapeutic target of TED.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"46"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11935560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673882","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":"EFEMP1-Mediated Regulation of Choroidal Vascular Dysfunction in Myopia: Insights Into the FOXO3/VEGFA Pathway as a Therapeutic Target.","authors":"Wen-Qing Shi, Bing Li, Yuting Shao, Wenting Han, Yule Xu, Qing Jiang, Shen Qu, Xiaodong Zhou, Yanlong Bi","doi":"10.1167/iovs.66.3.43","DOIUrl":"10.1167/iovs.66.3.43","url":null,"abstract":"<p><strong>Purpose: </strong>This study investigates the role of EFEMP1 in choroidal vascular dysfunction and its implications for myopia progression, specifically focusing on the FOXO3/VEGFA signaling pathway as a potential therapeutic target.</p><p><strong>Methods: </strong>We utilized adeno-associated virus (AAV) to overexpress and knock down EFEMP1 in the choroid of guinea pigs. Subsequent proteomic analyses were conducted on the choroidal tissue. We used Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to identify relevant pathways and genes. In vitro experiments were performed on RF/6A cells, where both EFEMP1 and FOXO3 underwent overexpression and knockdown. We conducted a series of cell culture experiments, including assessments of cell proliferation, migration, tube formation, and choroidal sprouting assays, to evaluate the functional effects of EFEMP1. Quantitative reverse transcription PCR and Western blot analyses were utilized to measure gene and protein expression levels.</p><p><strong>Results: </strong>Silencing EFEMP1 significantly reduced choroidal vascular dysfunction and slowed the progression of myopia. Proteomic analysis demonstrated that EFEMP1 regulates FOXO3 activity, resulting in increased VEGFA expression in RF/6A cells and promoting angiogenesis. Conversely, knockdown of FOXO3 led to decreased VEGFA levels, confirming that EFEMP1 modulates VEGFA expression through FOXO3.</p><p><strong>Conclusions: </strong>Targeting EFEMP1 may offer a novel therapeutic strategy for the prevention and treatment of myopia by alleviating associated vascular dysregulation. Further exploration of the FOXO3/VEGFA pathway could provide additional insights into therapeutic interventions for myopia.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"43"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663361","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":"Reversal of Diabetic Dry Eye by Topical Opioid Receptor Blockade Follows Dual Pathways.","authors":"David Diaz, Joseph W Sassani, Ian S Zagon, Patricia J McLaughlin","doi":"10.1167/iovs.66.3.24","DOIUrl":"10.1167/iovs.66.3.24","url":null,"abstract":"<p><strong>Purpose: </strong>To determine pathways in the trigeminal ganglion and corneal epithelium that are targeted by topical naltrexone (NTX) treatment for dry eye.</p><p><strong>Methods: </strong>NTX drops were administered topically daily for 15 days to the corneal surface of male and female adult type 1 diabetic rats. Schirmer scores and corneal sensitivity were measured at baseline, 5, 10, and 15 days. Trigeminal ganglion and corneal epithelium were processed for immunohistochemistry to detect expression of opioid growth factor receptor (OGFr), Ki67, nerve growth factor, insulin-like growth factor-1, calcitonin gene-related peptide, substance P, and TNF-α. A proteomic study determined protein changes in the cornea.</p><p><strong>Results: </strong>Corneal sensitivity and tear production in diabetic rats were restored to normal levels within 5 days after topical NTX. Assessment of corneal tissue after 15 days of treatment revealed that defects in OGFr expression, epithelial cell number, and Ki67+ expression were restored to normal by NTX. Inflammation markers (e.g., TNF-α) were reduced in tissue from diabetic rats treated with NTX. Proteomic data suggest diabetes causes dysregulation in inflammatory biological processes. The percentages of calcitonin gene-related peptide-positive neurons, but not substance P-positive neurons, in the trigeminal ganglion were increased after NTX treatment. Diabetic male and female rats responded to NTX in a comparable manner.</p><p><strong>Conclusions: </strong>Type 1 diabetes results in decreased tear production and altered corneal surface sensitivity. These complications coincide with dysregulated OGFr that maintains ocular homeostasis. Reversal of dry eye and restoration of corneal sensitivity in diabetic male and female rats after 15 days of topical treatment with NTX occur following dual pathways of increased cellular proliferation and reduction of inflammation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"24"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585697","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":"Dicer Loss in Müller Glia Leads to a Defined Sequence of Pathological Events Beginning With Cone Dysfunction.","authors":"Daniel Larbi, Alexander M Rief, Seoyoung Kang, Shaoheng Chen, Khulan Batsuuri, Sabine Fuhrmann, Suresh Viswanathan, Stefanie G Wohl","doi":"10.1167/iovs.66.3.7","DOIUrl":"10.1167/iovs.66.3.7","url":null,"abstract":"<p><strong>Purpose: </strong>The loss of Dicer in Müller glia (MG) results in severe photoreceptor degeneration, as it occurs in retinitis pigmentosa or age-related macular degeneration; however, the sequence of events leading to this severe degenerative state is unknown. The aim of this study was to conduct a chronological functional and structural characterization of the pathological events in MG-specific Dicer-conditional knockout (cKO) mice in vivo and histologically.</p><p><strong>Methods: </strong>To delete Dicer and mature microRNAs (miRNAs) in MG, two conditional Dicer1 knockout mouse strains (Rlbp-CreER:tdTomato:Dicer-cKOMG and Glast-CreER:tdTomato:Dicer-cKOMG) were created. Optical coherence tomography (OCT), electroretinograms (ERGs), and histological analyses were conducted to investigate structural and functional changes up to 6 months after Dicer deletion.</p><p><strong>Results: </strong>Dicer/miRNA loss in MG leads to (1) impairments of the area spanning from the external limiting membrane (ELM) to the retinal pigment epithelium (RPE), (2) cone photoreceptor dysfunction, and (3) retinal remodeling and functional loss of the inner retina at 1, 3, and 6 months after Dicer loss, respectively, in both of the knockout mouse strains. Furthermore, in the Rlbp-CreER:tdTomato:Dicer-cKOMG strain, rod photoreceptor impairment was found 4 months after Dicer depletion (4) accompanied by alteration of RPE integrity (5).</p><p><strong>Conclusions: </strong>MG Dicer loss in the adult mouse retina impacts cone function prior to any measurable changes in rod function, suggesting a pivotal role for MG Dicer and miRNAs in supporting cone health. A partially impaired RPE, however, seems to accelerate rod degeneration and overall degenerative events.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 3","pages":"7"},"PeriodicalIF":5.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541497","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}