Investigative ophthalmology & visual science最新文献

{"title":"Comprehensive Visualization of Choroidal Alterations in Thyroid Eye Disease With Ultra-Widefield OCT Angiography.","authors":"Yi Wang, Tengbo Rao, Jichao Zhou, Debo You, Jiarui Yang, Lingge Suo","doi":"10.1167/iovs.66.2.25","DOIUrl":"10.1167/iovs.66.2.25","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate choroidal and optic disc alterations in eyes with thyroid eye disease (TED) compared with healthy eyes by using TowardPi widefield optical coherence tomography angiography (OCTA).</p><p><strong>Methods: </strong>This was a retrospective cross-sectional cohort study. A total of 112 participants (60 TED patients and 52 healthy controls) underwent TowardPi widefield OCTA, which provided detailed demographic and clinical data. Three-dimensional choroidal data, including thickness, vascular metrics, and optic disc measurements, were obtained from the built-in software.</p><p><strong>Results: </strong>The study included 24 eyes with dysthyroid optic neuropathy (DON), 24 eyes with active non-DON TED, 71 eyes with inactive TED, and 104 healthy eyes. Choroidal thickness significantly decreased in the optic disc region during the DON phase (148.71 ± 78.98 µm) compared to normal eyes (182.35 ± 51.98 µm) and inactive TED eyes (191.34 ± 58.86 µm) (P = 0.030). In DON, choroidal stromal volume was reduced (34,183.81 ± 10,649.01 × 106 µm3) compared to normal (46,339.53 ± 16,711.99 × 106 µm3) (P = 0.002), whereas the choroidal vascular index increased (42.67% ± 3.41%) compared to normal (38.53% ± 6.35%) (P = 0.002). Optic disc area increased in DON (1.99 ± 1.24 mm2) compared to inactive TED (1.39 ± 0.38 mm2) (P < 0.001), along with reduced retinal nerve fiber layer blood-flow density in DON (45.09% ± 3.07%,) compared to normal (47.84% ± 1.41%) (P < 0.001).</p><p><strong>Conclusions: </strong>This study highlights the critical role of choroidal and optic disc alterations in TED pathophysiology and underscore the utility of widefield OCTA in identifying these changes, particularly in DON-risk patients.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"25"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382011","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":"Photoreceptor Function and Structure in Retinal Areas With Intraretinal Hyperreflective Foci in Age-Related Macular Degeneration.","authors":"Xiaolin Wang, Sujin Hoshi, Ruixue Liu, Giulia Corradetti, Michael Ip, David Sarraf, SriniVas R Sadda, Yuhua Zhang","doi":"10.1167/iovs.66.2.27","DOIUrl":"10.1167/iovs.66.2.27","url":null,"abstract":"<p><strong>Purpose: </strong>To assess retinal light sensitivity in regions with intraretinal hyperreflective foci (IHRFs) in eyes with intermediate age-related macular degeneration (AMD) and examine the photoreceptor structure in these areas using adaptive optics scanning laser ophthalmoscopy (AOSLO) and optical coherence tomography (OCT).</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 82 eyes of 57 subjects (age: 76.4 ± 7.0 years) with intermediate AMD. IHRFs were identified in OCT B-scans. Drusen and subretinal drusenoid deposits (SDDs) were evaluated using multimodal imaging. Photoreceptor structure was assessed with AOSLO, and choroidal and retinal thicknesses were measured in areas with IHRFs. In 16 eyes, mesopic and scotopic light sensitivities were compared in regions with and without IHRFs but with similar SDD/drusen load in the same eye.</p><p><strong>Results: </strong>Retinal areas with IHRFs had significantly reduced mesopic (17.19 ± 5.68 dB vs. 18.49 ± 5.35 dB, P = 0.0029) and scotopic (8.39 ± 5.67 dB vs. 9.72 ± 6.28 dB, P = 0.0096) light sensitivity compared to areas without IHRFs. AOSLO revealed disrupted cone photoreceptor structure in IHRF regions. Choroidal thickness beneath areas with IHRFs was thinner than in those without IHRFs (196.71 ± 73.31 µm vs. 202.37 ± 70.64 µm, P = 0.0211). Retinal thickness in regions with IHRFs was not significantly different from those without IHRFs (320.40 ± 31.16 µm vs. 316.92 ± 26.32 µm, P = 0.3537).</p><p><strong>Conclusions: </strong>IHRF presence is associated with localized reduced visual function and photoreceptor degeneration in intermediate AMD. Prospective studies are warranted to further investigate the mechanisms of photoreceptor and sensitivity loss in the context of IHRF.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"27"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382304","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":"Genotype-Phenotype Spectrum of eyeGENE Patients With Familial Exudative Vitreoretinopathy: Novel Variants in Norrin/β-Catenin Signaling Pathway Genes.","authors":"Fulya Yaylacioglu Tuncay, Melissa J Reeves, Sairah Yousaf, Ehsan Ullah, Bin Guan, Kerry E Goetz, Santa J Tumminia, Robert B Hufnagel","doi":"10.1167/iovs.66.2.9","DOIUrl":"10.1167/iovs.66.2.9","url":null,"abstract":"<p><strong>Purpose: </strong>To report the variants and genotype-phenotype correlations in patients with familial exudative vitreoretinopathy (FEVR) included in the eyeGENE database.</p><p><strong>Methods: </strong>A retrospective study was conducted in a cohort of 122 eyeGENE patients from 114 families with FEVR. Clinical details and genetic test results were provided by referring clinicians and clinical laboratories in the eyeGENE network, respectively. Genotype and phenotype information was reviewed, and reported variants were reclassified.</p><p><strong>Results: </strong>Genetic test reports of 50 probands revealed 52 variants in the four genes of the Norrin/β-catenin signaling pathway: LRP5, FZD4, TSPAN12, and NDP. Following variant reclassification, 35 of the reported variants were interpreted as pathogenic or likely pathogenic (12 in LRP5, 11 in FZD4, seven in TSPAN12 and five in NDP), providing a conclusive test result for nearly one-third (32%) of the probands. Among the reported variants, 18 were novel (34.6%) and two-thirds were missense. Retinal detachment was reported less in patients with variants in TSPAN12 (P = 0.017). One-third of the patients (33.3%) with an FZD4 variant had asymmetric findings. In contrast, asymmetry was less pronounced in patients with variants in TSPAN12 (11.1%).</p><p><strong>Conclusions: </strong>This was one of the largest cohorts reviewed from North America, expanding the variant spectrum in FEVR. Among the eyeGENE FEVR patients, disease-associated variants in Norrin/β-catenin signaling pathway genes can explain one-third of the cohort. LRP5 and FZD4 variants were the most common. The genotype-phenotype correlations supported the phenotypic variability in FEVR.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"9"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189307","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":"Targeted Microperimetry Grids for Focal Lesions in Intermediate AMD: PINNACLE Study Report 7.","authors":"Stefan Futterknecht, Philipp Anders, Julia Mai, Sophie Riedl, Ursula Hall, Chrysoula Gabrani, Kristina Pfau, Martin J Menten, Daniel Rueckert, A Toby Prevost, Hrvoje Bogunovic, Lars G Fritsche, Ursula Schmidt-Erfurth, Sobha Sivaprasad, Andrew Lotery, Hendrik P N Scholl, Maximilian Pfau","doi":"10.1167/iovs.66.2.6","DOIUrl":"10.1167/iovs.66.2.6","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate the feasibility and utility of optical coherence tomography (OCT)-based, targeted microperimetry grids in assessing focal lesions in intermediate age-related macular degeneration (iAMD).</p><p><strong>Methods: </strong>The multicenter, prospective PINNACLE study enrolled 395 patients with iAMD aged 55 to 90 years across 12 international sites. Participants underwent imaging, including OCT and microperimetry, every 4 to 12 months over 3 years. Deep learning algorithms detected focal lesions and changes in OCT images, including drusen regression, EZ/IZ loss with hypertransmission, and subretinal fluid, guiding 5-point microperimetry targeted to lesion locations. Data were analyzed using linear mixed models to estimate differences between retinal sensitivity measured by the 5-point focal grids and sensitivity interpolated from the 24-point standard grids.</p><p><strong>Results: </strong>The final analysis included 93 eyes from 83 patients, assessing 605 of the 5-point targeted grids and standard grids across 235 focal lesions. The Pearson correlation between focally measured sensitivity and interpolated sensitivity was 0.76. However, interpolation from the standard grid could be erroneous, especially in central regions of lesions characterized by EZ/IZ loss with hypertransmission and subretinal fluid. Interpolation errors increased with distance to the nearest measurement point (slope = 2.20 dB per degree, 95% confidence interval [CI] = 1.52 to 2.87). A significant negative relationship was found between interpolation errors and retinal sensitivity, with the highest errors in areas of low sensitivity. Lesion size significantly impacted interpolation errors for EZ/IZ loss with hypertransmission (slope = -19.41 dB/mm², 95% CI = -29.63 to -9.18).</p><p><strong>Conclusions: </strong>Targeted grids improved the detection and understanding of how focal retinal changes affect visual function in patients with iAMD, supporting the development of therapeutic interventions.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"6"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11801386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189326","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":"Single and Multiple Visual Function Impairments and Associated- Vision-Related Quality of Life Impact in Older Adults Aged 60 to 100 Years.","authors":"Preeti Gupta, Tai Anh Vu, Chiew Meng Johnny Wong, Sahil Thakur, Alex A Black, Joanne M Wood, Ryan E K Man, Eva K Fenwick, Ecosse L Lamoureux","doi":"10.1167/iovs.66.2.18","DOIUrl":"10.1167/iovs.66.2.18","url":null,"abstract":"<p><strong>Purpose: </strong>Determine the prevalence and vision-related quality of life (VRQoL) effects of single and multiple visual function impairments (VFIs) in multi-ethnic older Asians.</p><p><strong>Methods: </strong>A total of 2380 participants from a population-based cohort study were included. Visual function comprised presenting visual acuity (VA), contrast sensitivity (CS), depth perception (DP), and color vision (CV). Rasch-transformed VRQoL was obtained using the Brief Impact of Visual Impairment questionnaire. Multiple linear regression explored the independent (mutually adjusting for each VFI) impact of bilateral single (VAI, CSI, CVI and DPI) and multiple (i.e., the co-occurrence of any two, three, or four bilateral VFI) VFIs on VRQoL. Dominance analysis estimated the relative contribution for each of the single VFI on VRQoL.</p><p><strong>Results: </strong>The prevalence of bilateral VAI, CSI, CVI, or DPI alone was 15.3%, 20.7%, 8.1%, and 23.5%, respectively, whereas for concurrent two, three and four bilateral VFIs was 11%, 4.1% and 1.6%, respectively. Participants with single bilateral VFI (except CVI) experienced poorer overall VRQoL (β -0.25 to -0.34; all p < 0.05) compared to those without. CSI had the largest contribution (25%), to the decline in overall VRQoL. As the number of concurrent bilateral VFIs increased, VRQoL progressively worsened (% decrements -12.26% to -25.61%; all P < 0.001) compared to no VFI.</p><p><strong>Conclusions: </strong>Bilateral single and multiple VFIs are prevalent in older Asians. CSI had the largest contribution to VRQoL decrements. There was a systematic worsening in VRQoL scores with an increase in concurrent bilateral VFI. Comprehensive visual function testing may be warranted to prevent the debilitating consequences of VFIs on healthy aging.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"18"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11806435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255703","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":"Lamp2 Deficiency Enhances Susceptibility to Oxidative Stress-Induced RPE Degeneration.","authors":"Guannan Wu, Shoji Notomi, Ziming Xu, Yosuke Fukuda, Yusuke Maehara, Yan Tao, Huanyu Zhao, Keijiro Ishikawa, Yusuke Murakami, Toshio Hisatomi, Koh-Hei Sonoda","doi":"10.1167/iovs.66.2.2","DOIUrl":"10.1167/iovs.66.2.2","url":null,"abstract":"<p><strong>Purpose: </strong>Autophagy and lysosomal degradation are vital processes that protect cells from oxidative stress. This study investigated the role of lysosome-associated membrane protein 2 (Lamp2), a lysosomal protein essential for autophagosome maturation and lysosome biogenesis, in maintaining retinal health under oxidative stress.</p><p><strong>Methods: </strong>To induce oxidative stress, young Lamp2 knockout (KO) and wild-type mice received an intravenous injection of a low dose (10 mg/kg) of sodium iodate (NaIO3). We examined retinal histopathology and morphological changes in the RPE. The involvement of resident microglia or infiltrating macrophages was assessed using immunostaining, flow cytometry, and real-time PCR for chemokines and cytokines.</p><p><strong>Results: </strong>After administering a low-dose NaIO3, Lamp2 KO mice showed significant RPE degeneration, whereas wild-type mice had minimal damage. Histological analysis and electron microscopy revealed significant thinning of the outer nuclear layer and loss of RPE epithelial polarity in Lamp2 KO mice. Additionally, there was a significant increase in ionized calcium-binding adaptor molecule 1-positive microglia and macrophages in the outer retina. Early proliferation of CD45lowMHC-IIlow resident microglia was followed by the infiltration of CD45highLy6Chigh monocytes and the engraftment of CD11b+CD45high monocyte-derived macrophages. Transcript levels of monocyte chemoattractant protein 1, macrophage inflammatory protein 1β, Il- 1β, and Il-6 also increased in the retinas of Lamp2 KO mice. Furthermore, pretreatment with the macrophage-depleting agent clodronate prevented NaIO3-induced RPE degeneration and macrophage infiltration in Lamp2 KO mice.</p><p><strong>Conclusions: </strong>Lamp2 deficiency, when combined with oxidative stress, leads to RPE degeneration in vivo. Lysosomal dysfunction also promotes macrophage engraftment and triggers neurotoxic inflammation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"2"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079757","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":"Molecular Subtype Identification and Potential Drug Prediction Based on Anoikis-Related Genes Expression in Keratoconus.","authors":"Zhixin Jiang, Boyang Zhang, Shichong Jia, Xiaoyong Yuan","doi":"10.1167/iovs.66.2.3","DOIUrl":"10.1167/iovs.66.2.3","url":null,"abstract":"<p><strong>Purpose: </strong>Anoikis is a special apoptosis accompanied by the loss of extracellular matrix (ECM) environment and the decomposition of ECM is an important process in the occurrence of keratoconus (KC). This study aims to describe the expression profile of anoikis-related genes (ARGs) in KC samples, identify differentially expressed genes (DEGs), characterize the biological functions and immune characteristics of different molecular subtypes of KC and predict potential drugs based on the construction of a co-expression network.</p><p><strong>Methods: </strong>First, we identified molecular subtypes by optimal clustering K based on the expression profile of ARGs in the KC dataset and analyzed the differences of functional and immune characteristics. Then a weighted gene co-expression network was constructed based on cluster analysis to obtain hub genes and protein-protein interaction network was constructed to analyze hub nodes and predict potential node-targeting drugs.</p><p><strong>Results: </strong>By comparing the expression profile between disease and normal samples, we found that there were significant differences in ARGs such as BCL2, CAV1, and CEACAM5. Consistent cluster analysis identified two definite clusters on the basis of ARGs expression difference. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis showed that DEGs were enriched significantly in pathways like ECM receptor interaction, chemokine signal, notch signal, focal adhesion, and functional sets like proteolysis, anoikis, regulation of natural killer and T-cell proliferation. CIBERSORT calculation showed that there were significant differences between the two subtypes on immune cell infiltration (monocytes and plasma) and immune molecules (CCL11, CCL14, HLA-A, HLA-B, and so on). Then, co-expression network was constructed based on cluster phenotype, 5202 genes were selected as hub genes, and 321 HubDEGs were obtained after intersection with significant DEGs. Seven hub nodes, EIF4G1, KHSRP, PABPC1, POLR2A, PTBP1, RPS19, and SMARCA4, were identified and matched drugs or small molecular compounds. Insulin and dexamethasone were identified as potential target drugs.</p><p><strong>Conclusions: </strong>We revealed the differential expression of ARGs in KC samples, and identified two distinct subtypes that showed significant differences in biological function and immune infiltration. The identification of hub gene nodes elucidated their therapeutic value on predicted potential drugs.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"3"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079872","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":"Disruption in Autonomic Nervous Activity Is Associated With Central and Peripheral-Level in Dry Eye With Unstable Tear Film.","authors":"Minako Kaido, Reiko Arita, Yasue Mitsukura, Brian Sumali, Kazuo Tsubota","doi":"10.1167/iovs.66.2.69","DOIUrl":"10.1167/iovs.66.2.69","url":null,"abstract":"<p><strong>Purpose: </strong>To measure autonomic nerve activity (ANA) in several eye conditions and verify whether ANA modulation is regulated by peripheral or central control in short tear film break-up time dry eye (sBUTDE).</p><p><strong>Methods: </strong>This study included 23 eyes of 23 patients with sBUTDE (mean age 55.2 ± 16.1 years; range 21-88 years) and 24 eyes of 24 age-matched non-dry eye (DE) controls. An ANA measurement, personality questionnaire, and Ocular Surface Disease Index were administered. ANA was continuously measured for 10 minutes under three conditions: eyes closed, eyes open, and eyes open under ocular surface anesthesia.</p><p><strong>Results: </strong>The low-frequency (LF)/high-frequency (HF) ratio (LF/HF) with eyes closed was significantly higher in the sBUTDE group than in the control group (P < 0.05). In the sBUTDE group, HF increased and LF/HF decreased with eye opening compared with those in the control group; HF with eyes open decreased with ocular surface anesthesia and reached the same level as that in the control group. Among patients where HF decreased or LF/HF increased with eye opening, 57.1% or 64.3% showed a tendency to return to the ANA state with eyes closed by ocular surface anesthesia, respectively. Factors associated with DE symptoms included break-up time, HF with eyes open, and \"openness\" (P < 0.05).</p><p><strong>Conclusions: </strong>ANA modulation can be caused by peripheral, central, or mixed abnormalities in sBUTDE. Furthermore, personality traits may play a role in symptom induction. Understanding the pathogenesis of sBUTDE may aid in the treatment of cases that are refractory to conventional treatments.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"69"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515632","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":"Comment on: \"Effects of Monocular Flicker on Binocular Imbalance in Amblyopic and Nonamblyopic Adults\".","authors":"Alexandre Reynaud","doi":"10.1167/iovs.66.2.29","DOIUrl":"10.1167/iovs.66.2.29","url":null,"abstract":"","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"29"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11817970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390888","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":"Expression of Osteopontin in M2 and M4 Intrinsically Photosensitive Retinal Ganglion Cells in the Mouse Retina.","authors":"Leonie Kinder, Moritz Lindner","doi":"10.1167/iovs.66.2.14","DOIUrl":"10.1167/iovs.66.2.14","url":null,"abstract":"<p><strong>Purpose: </strong>Melanopsin-expressing intrinsically photosensitive (ip) retinal ganglion cells (RGCs) can be divided into six different subtypes (M1 - M6). Yet, specific markers exist for only some of these subtypes that could be employed to study the function of individual subtypes. Osteopontin (Spp1) marks αRGC, suggesting that, across ipRGCs, it would only mark the M4-ipRGC subtype (synonymous to ON-sustained αRGCs). Recent evidence suggests that osteopontin expression could spread to other ipRGC subtypes. Therefore, this study aims to characterize the expression pattern of osteopontin across ipRGC subtypes in mice.</p><p><strong>Methods: </strong>Single-cell RNA (scRNA-seq) sequencing data from murine RGCs were analyzed to identify expression patterns of Spp1 across ipRGCs. Immunohistochemistry (IHC) was performed on retinal cryosections and flatmounts from C57BL/6J mice to characterize the localization of osteopontin across ipRGCs. Neurite tracing was employed to study dendritic morphology and identify individual ipRGC subtypes.</p><p><strong>Results: </strong>scRNA-seq analysis revealed Spp1 expression in two distinct clusters of ipRGCs. IHC confirmed osteopontin colocalization with neurofilament heavy chain, an established marker for αRGCs, including M4-ipRGCs. Spp1 immunoreactivity was moreover identified in one additional group of ipRGCs. By dendritic morphology and stratification, those cells were clearly identified as M2-ipRGCs.</p><p><strong>Conclusions: </strong>Our findings demonstrate that osteopontin is expressed in both M2- and M4-ipRGCs, challenging the notion of osteopontin as a marker exclusively for αRGCs. IHC double-labeling for osteopontin and melanopsin provides a novel method to identify and differentiate M2 ipRGCs from other subtypes. This will support the study of ipRGC physiology in a subtype -specific manner and may, for instance, foster research in the field of optic nerve injury.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"66 2","pages":"14"},"PeriodicalIF":5.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255606","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}