Investigative ophthalmology & visual science最新文献

{"title":"Host-Graft Synapses Form Functional Microstructures and Shape the Host Light Responses After Stem Cell-Derived Retinal Sheet Transplantation.","authors":"Ryutaro Akiba, Hung-Ya Tu, Tomoyo Hashiguchi, Yoshiko Takahashi, Kiminori Toyooka, Yoshihiko Tsukamoto, Takayuki Baba, Masayo Takahashi, Michiko Mandai","doi":"10.1167/iovs.65.12.8","DOIUrl":"10.1167/iovs.65.12.8","url":null,"abstract":"<p><strong>Purpose: </strong>Retinitis pigmentosa represents a leading cause of blindness in developed countries, yet effective treatments for the disease remain unestablished. Previous studies have demonstrated the potential of stem cell-derived retinal organoid (SC-RO) sheet transplantation to form host-graft synapses and to improve light responsiveness in animal models of retinal degeneration. However, the detailed microstructures of these de novo synapses and their functional contribution have not been well elucidated. This study aims to (1) elucidate the microstructures of the host-graft synapse, and (2) investigate the overall distribution and contribution of these synapses to host retinal light responses.</p><p><strong>Methods: </strong>We identified host-graft synapses using a reporter system in mouse SC-RO and rd1 mice, a well-established model of end-stage retinal degeneration. Correlative array tomography was used to reveal the microstructure of host-graft synapses. Furthermore, we developed a semi-automated algorithm that robustly detects the host-graft photoreceptor synapses in the overall grafted area using the same reporter system in flat-mount retinas. We then integrated the spatial distribution of the host-graft synapses with light responses detected by multi-electrode array recording.</p><p><strong>Results: </strong>Correlative array tomography revealed that host-graft synapses recapitulate the developmental process of photoreceptor synapse formation involving horizontal cells first and then rod bipolar cells. By integrating the spatial distribution of host-graft synapse and multi-electrode array recording, we showed that the number of light-responsive host retinal ganglion cells is positively correlated with the local density of host-graft synapses.</p><p><strong>Conclusions: </strong>De novo host-graft synapses recapitulate the developmental microstructure of the photoreceptor synapse, and their formation contributes to the light responsiveness after SC-RO transplantation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"8"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463710/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380868","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":"DAMPs Drive Fibroinflammatory Changes in the Glaucomatous ONH.","authors":"Emma K Geiduschek, Emma K Bricco, Colleen M McDowell","doi":"10.1167/iovs.65.12.13","DOIUrl":"10.1167/iovs.65.12.13","url":null,"abstract":"<p><strong>Purpose: </strong>The optic nerve head (ONH) is well known to be the initial site of glaucomatous damage; however, the molecular mechanisms initiating this pathology are not fully understood. To further understand the initiating factors in glaucomatous damage we utilized a novel mouse model of glaucoma, B6.EDA+/+ mice, which constitutively express fibronectin containing the extra domain A (FN+EDA). FN+EDA is a known damage-associated molecular pattern (DAMP) that activates Toll-like receptor 4 and elicits a fibro-inflammatory response.</p><p><strong>Methods: </strong>Eyes from B6.EDA+/+ and C57BL/6J mice were evaluated for retinal ganglion cell (RGC) death, retinal nerve fiber layer (RNFL) thickness, and optic nerve (ON) damage at 12 months and 22 months of age. ONH sections were isolated using laser capture microdissection for subsequent RNA-sequencing and Gene Set Enrichment Analysis (GSEA). GSEA results were confirmed using immunohistochemical (IHC) staining.</p><p><strong>Results: </strong>B6.EDA+/+ mice exhibit significantly higher intraocular pressure, loss of RGCs, thinning of the RNFL, and progressive levels of ON damage at 12 months and 22 months of age compared to C57BL/6J controls. Protein expression of DAMPs FN+EDA and biglycan was significantly increased in B6.EDA+/+ mice compared to C57BL/6J controls. GSEA analysis identified significantly up- and downregulated gene groupings at both 12 months and 22 months of age, and IHC staining at 12 and 18 months of age demonstrated significant increases of IFNα, IFNβ, and pSTAT1 expression in B6.EDA+/+ mice compared to C57BL/6J controls.</p><p><strong>Conclusions: </strong>Our study characterizes glaucomatous changes to the retina, ON, and ONH over the course of 2 years and identifies novel molecular pathways associated with these pathophysiological changes. These data illustrate the effects of FN+EDA on the fibro-inflammatory response in the aging ONH in a novel mouse model of glaucoma.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"13"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11469284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390589","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":"Aberrant Lipid Metabolism and Complement Activation in Age-Related Macular Degeneration.","authors":"Siao Tang, Jiaqi Yang, Bingqing Xiao, Yani Wang, Yiou Lei, Dongwei Lai, Qinghua Qiu","doi":"10.1167/iovs.65.12.20","DOIUrl":"https://doi.org/10.1167/iovs.65.12.20","url":null,"abstract":"<p><p>Age-related macular degeneration (AMD) stands as a leading cause of severe visual impairment and blindness among the elderly globally. As a multifactorial disease, AMD's pathogenesis is influenced by genetic, environmental, and age-related factors, with lipid metabolism abnormalities and complement system dysregulation playing critical roles. This review delves into recent advancements in understanding the intricate interaction between these two crucial pathways, highlighting their contribution to the disease's progression through chronic inflammation, drusen formation, and retinal pigment epithelium dysfunction. Importantly, emerging evidence points to dysregulated lipid profiles, particularly alterations in high-density lipoprotein levels, oxidized lipid deposits, and intracellular lipofuscin accumulation, as exacerbating factors that enhance complement activation and subsequently amplify tissue damage in AMD. Furthermore, genetic studies have revealed significant associations between AMD and specific genes involved in lipid transport and complement regulation, shedding light on disease susceptibility and underlying mechanisms. The review further explores the clinical implications of these findings, advocating for a novel therapeutic approach that integrates lipid metabolism modulators with complement inhibitors. By concurrently targeting these pathways, the dual-targeted approach holds promise in significantly improving outcomes for AMD patients, heralding a new horizon in AMD management and treatment.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"20"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465668","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":"Mouse Corneal Immune Cell Heterogeneity Revealed by Single-Cell RNA Sequencing.","authors":"Ebru Yaman, Nicole Heyer, Cintia S de Paiva, Mary Ann Stepp, Stephen C Pflugfelder, Jehan Alam","doi":"10.1167/iovs.65.12.29","DOIUrl":"10.1167/iovs.65.12.29","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to define the heterogeneity, spatial localization, and functional roles of immune cells in the mouse cornea using single-cell RNA sequencing (scRNA-seq) and immunofluorescent staining.</p><p><strong>Methods: </strong>Enriched mouse corneal immune cells (C57BL/6 strain, age 16-20 weeks) underwent single-cell RNA sequencing library preparation, sequencing, and analysis with Seurat, Monocle 3, and CellChat packages in R. Pathway analysis used Qiagen Ingenuity Pathway Analysis software. Immunostaining confirmed cell distribution.</p><p><strong>Results: </strong>We identified 14 distinct immune cell clusters (56% myeloid and 44% lymphoid). Myeloid populations included resident macrophages, conventional dendritic cells (cDC2s), Langerhans cells, neutrophils, monocytes, and mast cells. Additionally, lymphocyte subsets (B, CD8, CD4, γδT, natural killer, natural killer T, and group 2 innate lymphoid cells) were found. We also found three new subtypes of resident macrophages in the cornea. Trajectory analysis suggested a differentiation pathway from monocytes to conventional dendritic cells, resident macrophages, and LCs. Intercellular communication network analysis using cord diagram identified amyloid precursor protein, chemokine (C-C motif) ligands (2, 3, 4, 6, 7, 9, and 12), Cxcl2, Mif, Tnf, Tgfb1, Igf1, and Il10 as prominent ligands involved in these interactions. Sexually dimorphic gene expression patterns were observed, with male myeloid cells expressing genes linked to immune regulation (Egr1, Foxp1, Mrc1, and Il1rn) and females showing higher expression of antigen presentation genes (Clic1, Psmb8, and Psmb9). Finally, immunostaining confirmed the spatial distribution of these cell populations within the cornea.</p><p><strong>Conclusions: </strong>This study unveils a diverse immune landscape in the mouse cornea, with evidence for cell differentiation and sex-based differences. Immunostaining validates the spatial distribution of these populations, furthering our knowledge of corneal immune function.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"29"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465683","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":"Accommodative and Vergence Responses to a Moving Stimulus in Concussion.","authors":"Jennifer X Haensel, Sophia Marusic, Kristin E Slinger, Carissa H Wu, Neerali Vyas, Christabel A Ameyaw Baah, Amber Hu, Joellen Leonen, Caitlyn Y Lew, Gayathri Srinivasan, Amir Norouzpour, Erin Jenewein, Siva Meiyeppen, Mitchell Scheiman, Aparna Raghuram, Tawna L Roberts","doi":"10.1167/iovs.65.12.45","DOIUrl":"10.1167/iovs.65.12.45","url":null,"abstract":"<p><strong>Purpose: </strong>Concussed adolescents often report visual symptoms, especially for moving targets, but the mechanisms resulting in oculomotor deficits remain unclear. We objectively measured accommodative and vergence responses to a moving target in concussed adolescents and controls.</p><p><strong>Methods: </strong>Thirty-two symptomatic concussed participants (mean age, 14.4 ± 2.6 years; mean days since concussion, 107 days; range, 36-273 days) and 32 healthy controls (mean age, 12.7 ± 2.1 years) viewed a movie binocularly (closed-loop) and monocularly (vergence open-loop), as well as a Difference of Gaussians (DoG) target binocularly (accommodation open-loop). The movie or DoG target sinusoidally moved toward and away from participants at a 0.1-hertz (Hz) frequency at four separate stimulus amplitudes (1.50 diopters [D], 1.00 D, 0.50 D, 0.25 D) around a 2.50-D midpoint. Accommodation and vergence were continuously measured at 50 Hz using the PowerRef 3. Fourier analysis was used to assess the response amplitudes at the 0.1-Hz frequency. A 2 × 3 analysis of variance with the factors group (concussed, control) and viewing condition (binocular, monocular, DoG) was conducted on response amplitudes.</p><p><strong>Results: </strong>Across groups, accommodative and vergence responses were significantly higher in binocular than monocular conditions (P < 0.001), but not DoG conditions. Compared to controls, concussed participants had significantly reduced monocular accommodative responses (P < 0.012; e.g., at 1.50 D, controls = 1.09 ± 0.47 D and concussed = 0.80 ± 0.36 D, P = 0.011). No group differences were observed for vergence responses in any viewing condition.</p><p><strong>Conclusions: </strong>Accommodative and vergence responses to the moving target were largely driven by disparity cues for both groups, with only minimal improvements in the presence of additional blur cues. Concussed participants showed reduced accommodative responses to a 0.1-Hz stimulus in monocular conditions, indicating mild accommodative deficits in the absence of disparity cues.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"45"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536200/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545488","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":"Characterizing Presumed Displaced Retinal Ganglion Cells in the Living Human Retina of Healthy and Glaucomatous Eyes.","authors":"Mary E Marte,Kazuhiro Kurokawa,HaeWon Jung,Yan Liu,Marcel T Bernucci,Brett J King,Donald T Miller","doi":"10.1167/iovs.65.11.20","DOIUrl":"https://doi.org/10.1167/iovs.65.11.20","url":null,"abstract":"PurposeThe purpose of this study was to investigate the large somas presumed to be displaced retinal ganglion cells (dRGCs) located in the inner nuclear layer (INL) of the living human retina. Whereas dRGCs have previously been studied in mammals and human donor tissue, they have never been investigated in the living human retina.MethodsFive young, healthy subjects and three subjects with varying types of glaucoma were imaged at multiple locations in the macula using adaptive optics optical coherence tomography. In the acquired volumes, bright large somas at the INL border with the inner plexiform layer were identified, and the morphometric biomarkers of soma density, en face diameter, and spatial distribution were measured at up to 13 degrees retinal eccentricity. Susceptibility to glaucoma was assessed.ResultsIn the young, healthy individuals, mean density of the bright, large somas was greatest foveally (550 and 543 cells/mm2 at 2 degrees temporal and nasal, respectively) and decreased with increasing retinal eccentricity (38 cells/mm2 at 13 degrees temporal, the farthest we measured). Soma size distribution showed the opposite trend with diameters and size variation increasing with retinal eccentricity, from 12.7 ± 1.8 µm at 2 degrees to 15.7 ± 3.5 µm at 13 degrees temporal, and showed evidence of a bimodal distribution in more peripheral locations. Within and adjacent to the arcuate defects of the subjects with glaucoma, density of the bright large somas was significantly lower than found in the young, healthy individuals.ConclusionsOur results suggest that the bright, large somas at the INL border are likely comprised of dRGCs but amacrine cells may contribute too. These somas appear highly susceptible to glaucomatous damage.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"10 1","pages":"20"},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142213054","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":"Quantitative Perfusion-Weighted Magnetic Resonance Imaging in Uveal Melanoma.","authors":"Lisa Klaassen, Myriam G Jaarsma-Coes, Marina Marinkovic, Gregorius P M Luyten, Coen R N Rasch, Teresa A Ferreira, Jan-Willem M Beenakker","doi":"10.1167/iovs.65.11.17","DOIUrl":"10.1167/iovs.65.11.17","url":null,"abstract":"<p><strong>Purpose: </strong>Perfusion-weighted imaging (PWI; magnetic resonance imaging [MRI]) has been shown to provide valuable biological tumor information in uveal melanoma (UM). Clinically used semiquantitative methods do not account for tumor pigmentation and eye movement. We hypothesize that a quantitative PWI method that incorporates these, provides a more accurate description of tumor perfusion than the current clinical method. The aim of this study was to test this in patients with UM before and after radiotherapy.</p><p><strong>Methods: </strong>Perfusion-weighted 3T MRIs were retrospectively analyzed in 47 patients with UM before and after radiotherapy. Tofts pharmacokinetic modeling was performed to determine vascular permeability (Ktrans), extracellular extravascular space (ve), and reflux rate (kep). These were compared with semiquantitative clinical parameters including peak intensity and outflow percentage.</p><p><strong>Results: </strong>The effect of tumor pigmentation on peak intensity and outflow percentage was statistically significant (P < 0.01) and relative peak intensity was significantly different between melanotic and amelanotic tumors (1.5 vs. 1.9, P < 0.01). Before radiotherapy, median tumor Ktrans was 0.63 min-1 (range = 0.06-1.42 min-1), median ve was 0.23 (range = 0.09-0.63), and median kep was 2.3 min-1 (range = 0.6-5.0 min-1). After radiotherapy, 85% showed a decrease in Ktrans and kep (P < 0.01). Changes in tumor pigmentation before and after radiotherapy were small and not significant (median increase in T1 of 33 ms, P = 0.55).</p><p><strong>Conclusions: </strong>Quantitative PWI parameters decreased significantly after radiotherapy and can therefore can serve as an early biomarker for treatment response assessment. However, due to the nonsignificant changes in tumor pigmentation before and after radiotherapy, the current semiquantitative method appears to be sufficiently sensitive for detection of changes in tumor perfusion.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 11","pages":"17"},"PeriodicalIF":5.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11385876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154088","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":"Ocular Accommodative and Pupillary Responses During Fixation on Augmented Reality With a Maxwellian Display.","authors":"Masakazu Hirota,Kakeru Sasaki,Kanako Kato,Ryota Nakagomi,Ryusei Takigawa,Chinatsu Kageyama,Seiji Morino,Makoto Suzuki,Toshifumi Mihashi,Atsushi Mizota,Takao Hayashi","doi":"10.1167/iovs.65.11.30","DOIUrl":"https://doi.org/10.1167/iovs.65.11.30","url":null,"abstract":"PurposeThis study aimed to investigate the changes in ocular refraction and pupillary diameter during fixation on augmented reality (AR) images using a Maxwellian display.MethodsTwenty-two healthy young volunteers (average age, 20.7 ± 0.5 years) wore a Maxwellian display device in front of their right eye and fixated on an asterisk displayed on both a liquid-crystal display (real target) and a Maxwellian display (AR target) for 29 seconds (real as a baseline for 3 seconds, AR for 13 seconds, and real for 13 seconds) at distances of 5.0, 0.5, 0.33, and 0.2 meters. A binocular open-view autorefractometer was used to measure the ocular refraction and pupillary diameter of the left eye.ResultsAccommodative (5.0 meters, 0.28 ± 0.29 diopter [D]; 0.5 meter, -0.12 ± 0.35 D; 0.33 meter, -0.43 ± 0.57 D; 0.2 meter, -1.20 ± 0.82 D) and pupillary (5.0 meters, 0.07 ± 0.22 mm; 0.5 meter, -0.08 ± 0.17 mm; 0.33 meter, -0.16 ± 0.20 mm; 0.2 meter, -0.25 ± 0.24 mm) responses were negative when the real target distances were farther away. The accommodative response was significantly and positively correlated with the pupillary response during fixation on the AR target (R2 = 0.187, P < 0.001).ConclusionsFixating on AR images using a Maxwellian display induces accommodative and pupillary responses. Accommodative responses depend on the distance between real objects. Overall, the Maxwellian display does not completely eliminate accommodation in real space.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"14 1","pages":"30"},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249886","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":"Altered Cell Clusters and Upregulated Aqp1 in Connexin 50 Knockout Lens Epithelium.","authors":"Chun-Hong Xia,William Lin,Rachel Li,Xinfang Xing,Guangdu Jack Shang,Haiwei Zhang,Xiaohua Gong","doi":"10.1167/iovs.65.11.27","DOIUrl":"https://doi.org/10.1167/iovs.65.11.27","url":null,"abstract":"PurposeTo characterize the heterogeneity and cell clusters of postnatal lens epithelial cells (LECs) and to investigate the downstream targets of connexin 50 (Cx50) in the regulation of lens homeostasis and lens growth. To determine differentially expressed genes (DEGs) in the connexin 50 knockout (Cx50KO) lens epithelial cells that shed light on novel mechanism underlying the cataract and small size of the Cx50KO lenses.MethodsSingle-cell RNA sequencing (scRNA-seq) of lens epithelial cells isolated from one-month-old Cx50KO and wild-type (WT) mice were performed. Differentially expressed genes were identified, and selected DEGs were further studied by quantitative real-time PCR (RT-qPCR) analysis and Western blot analysis.ResultsThe expression profiles of several thousand genes were identified by scRNA-seq data analysis. In comparison to the WT control, many DEGs were identified in the Cx50KO lens epithelial cells, including growth regulating transcriptional factors and genes encoding water channels. Significantly upregulated aquaporin 1 (Aqp1) gene expression was confirmed by RT-qPCR, and upregulated AQP1 protein expression was confirmed by Western blot analysis and immunostaining both in vivo and in vitro.ConclusionsLens epithelial cells exhibit an intrinsic heterogeneity of different cell clusters in regulating lens homeostasis and lens growth. Upregulated Aqp1 in Cx50KO lens epithelial cells suggests that both connexin 50 and AQP1 likely play important roles in regulating water homeostasis in lens epithelial cells.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"53 1","pages":"27"},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249907","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":"The Effects of STRA6 Regulation of the Circadian Rhythm on Choroidal Neovascularization.","authors":"Ying Yang,Shenglai Zhang,Shu Su,Xiaowei Yang,Jia Chen,Aimin Sang","doi":"10.1167/iovs.65.11.21","DOIUrl":"https://doi.org/10.1167/iovs.65.11.21","url":null,"abstract":"PurposeThis study aims to investigate the relationship among STRA6, circadian rhythm, and choroidal neovascularization (CNV) formation, as well as the regulatory mechanism of STRA6 in CNV under circadian rhythm disturbances.MethodsC57BL/6J male mice (aged 6 weeks) were randomly divided into control and jet lag groups (using a time shift method every 4 days to disrupt the molecular clock's capacity to synchronize with a stable rhythm). A laser-induced CNV model was established in both the control and the jet lag group after 2 weeks of jet lag. The size of CNV lesions and vascular leakage were detected by morphological and imaging examination on the seventh day post laser. STRA6 was screened by full transcriptome sequencing. Bioinformatics analysis was conducted to assess the variation and association of STRA6 in the GSE29801 dataset. The effects of STRA6 were evaluated both in vivo and in vitro. The pathway mechanism was further elucidated and confirmed through immunofluorescence of paraffin sections and Western blotting.ResultsThe disturbance of circadian rhythm promotes the formation of CNV. Patients with age-related macular degeneration (AMD) exhibited higher levels of STRA6 expression compared to the control group, and STRA6 was enriched in pathways related to angiogenesis. In addition, CLOCK and BMAL1, which are initiators that drive the circadian cycle, had regulatory effects on STRA6. Knocking down STRA6 reversed the promotion of CNV formation caused by circadian rhythm disturbance in vivo, and it also affected the proliferation, migration, and VEGF secretion of RPE cells without circadian rhythm in vitro, as well as impacting endothelial cells. Through activation of the JAK2/STAT3/VEGFA signaling pathway in unsynchronized RPE cells, STRA6 promotes CNV formation.ConclusionsThis study suggests that STRA6 reduces CNV production by inhibiting JAK2/STAT3 phosphorylation after circadian rhythm disturbance. The results suggest that STRA6 may be a new direction for the treatment of AMD.","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"15 1","pages":"21"},"PeriodicalIF":4.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249912","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}