Investigative ophthalmology & visual science最新文献

{"title":"Proposing a Methodology for Axon-Centric Analysis of IOP-Induced Mechanical Insult.","authors":"Manik Bansal, Bingrui Wang, Susannah Waxman, Fuqiang Zhong, Yi Hua, Yuankai Lu, Juan Reynaud, Brad Fortune, Ian A Sigal","doi":"10.1167/iovs.65.13.1","DOIUrl":"https://doi.org/10.1167/iovs.65.13.1","url":null,"abstract":"<p><strong>Purpose: </strong>IOP-induced mechanical insult on retinal ganglion cell axons within the optic nerve head (ONH) is believed to be a key factor in axonal damage and glaucoma. However, most studies focus on tissue-level mechanical deformations, overlooking that axons are long and thin, and that their susceptibility to damage likely depends on the insult's type (e.g. stretch/compression) and orientation (longitudinal/transverse). We propose an axon-centric approach to quantify IOP-induced mechanical insult from an axon perspective.</p><p><strong>Methods: </strong>We used optical coherence tomography (OCT) scans from a healthy monkey eye along with histological images of cryosections to reconstruct the axon-occupied volume including detailed lamina cribrosa (LC) pores. Tissue-level strains were determined experimentally using digital volume correlation from OCT scans at baseline and elevated IOPs, then transformed into axonal strains using axon paths estimated by a fluid mechanics simulation.</p><p><strong>Results: </strong>Axons in the LC and post-LC regions predominantly experienced longitudinal compression and transverse stretch, whereas those in the pre-LC and ONH rim mainly suffered longitudinal stretch and transverse compression. No clear patterns were observed for tissue-level strains.</p><p><strong>Conclusions: </strong>Our approach allowed discerning axonal longitudinal and transverse mechanical insults, which are likely associated with different mechanisms of axonal damage. The technique also enabled quantifying insult along individual axon paths, providing a novel link relating the retinal nerve fiber layer and the optic nerve through the LC via individual axons. This is a promising approach to establish a clearer connection between IOP-induced insult and glaucoma. Further studies should evaluate a larger cohort.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568591","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":"Treatment of Conjunctival Melanoma Cell Lines With a Light-Activated Virus-Like Drug Conjugate Induces Immunogenic Cell Death.","authors":"Sen Ma, Ruben V Huis In't Veld, Elisabet de Los Pinos, Ferry A Ossendorp, Martine J Jager","doi":"10.1167/iovs.65.13.3","DOIUrl":"https://doi.org/10.1167/iovs.65.13.3","url":null,"abstract":"<p><strong>Purpose: </strong>Conjunctival melanoma (CJM) is a rare malignant ocular surface tumor, which often leads to local recurrences and metastases. In murine models of subcutaneous tumors, treatment with a novel virus-like drug conjugate (VDC; Bel-sar) showed a dual mechanism of action with direct tumor cell killing as well as stimulation of an antitumoral immune response. Bel-sar is currently being evaluated for the treatment of primary uveal melanoma and indeterminate nevi in a phase III clinical trial. We determined whether Bel-sar also has direct antitumor efficiency and a potential immunostimulatory capacity in CJM cells.</p><p><strong>Methods: </strong>Three human tumor-derived CJM lines were used. Bel-sar's subcellular and intracellular locations were determined with tracers. Following light activation of Bel-sar, cytotoxicity and exposure of damage-associated molecular patterns (DAMPs) were assessed. Treated tumor cells were co-cultured with THP-1 derived macrophages to assess tumor-cell phagocytosis.</p><p><strong>Results: </strong>Bel-sar was bound and internalized by CJM cells and subsequently found in the cell membrane, lysosome, Golgi apparatus, and mitochondria. Bel-sar activation induced near complete cell death with half-maximal inhibitory concentration (IC50) values between 30 pM and 60 pM. Finally, light-activated Bel-sar enhanced exposure of DAMPs, including calreticulin, heat shock protein 90, and stimulated phagocytosis by macrophages.</p><p><strong>Conclusions: </strong>Treatment with a novel VDC (Bel-sar) induced pro-immunogenic cell death in all three CJM cell lines. The in vitro cytotoxicity was accompanied by exposure of DAMPs, suggesting Bel-sar is a potential treatment for CJM by a dual mechanism of action. This dual mechanism may provide a targeted and direct killing of tumor cells and induce an immune response which might decrease local recurrences and metastasis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568644","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":"Retinal Function in Advanced Multiple Sclerosis.","authors":"James V M Hanson, Sara Single, Rahel B Eberle, Veronika Kana, Benjamin V Ineichen, Christina Gerth-Kahlert","doi":"10.1167/iovs.65.13.2","DOIUrl":"https://doi.org/10.1167/iovs.65.13.2","url":null,"abstract":"<p><strong>Purpose: </strong>People with multiple sclerosis (pwMS) experience autoimmunity-mediated inflammation and neurodegeneration throughout the central nervous system. There remains a need for clinically accessible, reliable functional markers of neurodegeneration in MS. Previous research has described changes to electroretinography (ERG)-derived measures of retinal bipolar cell function in pwMS early in the disease course. We, therefore, investigated ERG as a potential outcome measure in individuals with more advanced disease.</p><p><strong>Methods: </strong>This cross-sectional observational study included pwMS with Expanded Disability Status Scale (EDSS) scores of ≥3.0 and healthy control (HC) participants who underwent ERG, optical coherence tomography, high- and low-contrast visual acuity measurement, and an ophthalmological examination. ERG findings in MS eyes with and without previous optic neuritis (MS +ON; MS -ON) were compared with those in HC eyes. Effects of EDSS, disease duration, ON, and treatment status on selected ERG outcomes were measured. Additional exploratory analyses assessed potential influences of MS phenotype and disease status (clinically active, radiologically active, and disease progression).</p><p><strong>Results: </strong>Delays to two ERG peak times (dark-adapted 3.0 b-wave; light-adapted flicker) were recorded in MS +ON and MS -ON eyes. No influences of EDSS score, disease duration, previous ON, or treatment status were observed. Exploratory analyses were consistent with no effects of MS phenotype or disease status.</p><p><strong>Conclusions: </strong>ERG findings are abnormal in individuals with moderate-severe disability caused by MS; however, these findings are not distinct from those observed earlier in the disease course. Although bipolar dysfunction appears to be common in pwMS throughout the disease course, ERG is likely not useful in monitoring or prognostication of MS.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568642","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":"Midperipheral Microvascular Defects and Their Associations With Vitreoretinal Abnormalities in Early-Stage Familial Exudative Vitreoretinopathy.","authors":"Juan Zhang, Lu Ruan, Chen Jiang, Qian Yang, Qing Chang, Xin Huang","doi":"10.1167/iovs.65.13.4","DOIUrl":"https://doi.org/10.1167/iovs.65.13.4","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate microvascular growth defects in the temporal midperipheral retina and their correlations with vitreoretinal microstructural abnormalities (VRMAs) in early-stage familial exudative vitreoretinopathy (FEVR).</p><p><strong>Methods: </strong>We enrolled 127 patients (127 eyes) with early-stage FEVR and 31 healthy subjects (31 eyes). Widefield optical coherence tomography angiography was conducted for all enrolled eyes. Vessel density (VD), vessel diameter index (VDI), and vessel index (VI; VD/VDI) of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in temporal midperiphery were further evaluated. The distance from the vessel sprouting point of the optic disc to the avascular area margin (Optic-AVA) was measured to assess retinal vascular dysplasia.</p><p><strong>Results: </strong>In early-stage FEVR, 61.42% of eyes showed retinal microvascular abnormalities (MVAs) in the temporal midperiphery, all combined with VRMAs. Common MVAs presented disordered vascular anastomoses in the SCP and capillary loss in the DCP, corresponding to deficient neuroretina. The preretinal vasculature (PRV) was detected in 36 eyes. VD and VI were lower in FEVR eyes compared to controls, whereas the VDI in the SCP was larger (all P < 0.001). Optic-AVA was positively correlated with VD and VI in both plexuses and negatively correlated with the VDI in the SCP. PRV existence was independently correlated with decreased VI in the DCP (odds ratio [OR] = 0.322; P < 0.001), and VRMA existence was independently correlated with decreased VI in SCP and DCP (SCP OR = 0.282, P = 0.010; DCP OR = 0.562, P = 0.002).</p><p><strong>Conclusions: </strong>MVAs in the temporal midperipheral retina were revealed. Microvascular loss may be correlated with Optic-AVA reduction, PRV, and the presence of VRMAs.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568576","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":"Retinal Pigment Epithelium Curvature Can Predict Late Age-Related Macular Degeneration.","authors":"Rene Cheung, Matt Trinh, Lisa Nivison-Smith","doi":"10.1167/iovs.65.12.7","DOIUrl":"10.1167/iovs.65.12.7","url":null,"abstract":"<p><strong>Purpose: </strong>Outer retinal band integrity strongly predicts late age-related macular degeneration (AMD). However, it is often assessed subjectively as \"continuity\" using inconsistent definitions. Alternatively, \"curvature\" of the outer retinal bands is a quantitative metric that strongly correlates with AMD biomarkers and can screen for intermediate AMD. We evaluated the prognostic ability of retinal pigment epithelium (RPE) and ellipsoid zone (EZ) curvature for late AMD against outer retinal band continuity, pigmentary abnormalities, reticular pseudodrusen, and drusen volume.</p><p><strong>Methods: </strong>Consecutive patients with intermediate AMD who progressed to late AMD (n = 17) or remained stable (n = 42) were recruited. RPE and EZ curvature were quantified as a ratio of their lengths over Bruch's membrane using the sinuosity method of assessing river curvature, where a ratio of ∼1 indicates no outer retinal pathology. RPE, EZ, and Bruch's membrane were manually segmented and their lengths automatically extracted. The primary outcomes were outer retinal sinuosity and the odds ratio of predicting late AMD.</p><p><strong>Results: </strong>Mean follow-up time for progressors and nonprogressors was 4.4 and 3.6 years. RPE sinuosity was strongly associated with pigmentary abnormalities (P = 0.001) and drusen volume (P = 0.004) but not reticular pseudodrusen (P = 0.28). RPE sinuosity >1.03 was the strongest predictor of late AMD developing within 5 years (15 [2.9-75]) and across the study period (25 [2.3-282]). Drusen volume >0.03 mm3 was the strongest predictor of progression within 2 years (33 [2.5-426]), and RPD could not independently predict progression within any time frame.</p><p><strong>Conclusions: </strong>RPE curvature is a promising, quantitative outer retinal biomarker that can prognosticate late AMD and potentially enhance prognostic models.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371860","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":"Exploring the Phenotype and Possible Mechanisms of Palinopsia in Visual Snow Syndrome.","authors":"Cassandra J Brooks, Joanne Fielding, Owen B White, David R Badcock, Allison M McKendrick","doi":"10.1167/iovs.65.12.23","DOIUrl":"https://doi.org/10.1167/iovs.65.12.23","url":null,"abstract":"<p><strong>Purpose: </strong>Palinopsia (persistent afterimages and/or trailing) is a common but poorly understood symptom of the neurological condition visual snow syndrome. This study aimed to collect a phenotypical description of palinopsia in visual snow syndrome and probe for abnormalities in temporal visual processing, hypothesizing that palinopsia could arise from increased visibility of normal afterimage signals or prolonged visible persistence.</p><p><strong>Methods: </strong>Thirty controls and 31 participants with visual snow syndrome (18 with migraine) took part. Participants completed a palinopsia symptom questionnaire. Contrast detection thresholds were measured before and after brief exposure to a spatial grating because deficient contrast adaptation could increase afterimage visibility. Temporal integration and segregation were assessed using missing-element and odd-element tasks, respectively, because prolonged persistence would promote integration at wide temporal offsets. To distinguish the effects of visual snow syndrome from comorbid migraine, 25 people with migraine alone participated in an additional experiment.</p><p><strong>Results: </strong>Palinopsia was common in visual snow syndrome, typically presenting as unformed images that were frequently noticed. Contrary to our hypotheses, we found neither reduced contrast adaptation (F(3.22, 190.21) = 0.71, P = 0.56) nor significantly prolonged temporal integration thresholds (F(1, 59) = 2.35, P = 0.13) in visual snow syndrome. Instead, participants with visual snow syndrome could segregate stimuli in closer succession than controls (F(1, 59) = 4.62, P = 0.04, ηp2 = 0.073) regardless of co-occurring migraine (F(2, 53) = 1.22, P = 0.30). In contrast, individuals with migraine alone exhibited impaired integration (F(2, 53) = 4.44, P = 0.017, ηp2 = 0.14).</p><p><strong>Conclusions: </strong>Although neither deficient contrast adaptation nor prolonged visible persistence explains palinopsia, temporal resolution of spatial cues is enhanced and potentially more flexible in visual snow syndrome.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488523/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465681","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":"Temporal Changes in the Retinal Pigment Epithelium-Bruch's Membrane Complex Thickness After Autologous Retinal Transplantation in Myopic Eyes.","authors":"Shohei Kitahata, Tatsuya Inoue, Shin Tanaka, Jacob Y H Chin, Satoru Shinoda, Maiko Maruyama-Inoue, Kazuaki Kadonosono","doi":"10.1167/iovs.65.12.25","DOIUrl":"10.1167/iovs.65.12.25","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the association between the thickness of the retinal pigment epithelium (RPE)-Bruch's membrane (BM) complex and the development of retinal autograft edema as a postoperative complication following autologous retinal transplantation (ART).</p><p><strong>Methods: </strong>This retrospective study examined data from 28 eyes of 28 patients (14 males, 14 females; mean age, 61.5 ± 19.8 years) who underwent ART and were followed for 1 year. The RPE-BM complex thickness was measured 2000 µm from the fovea using Image J software. Additionally, the graft blood flow was also evaluated by optical coherence tomography angiography and fluorescein angiography.</p><p><strong>Results: </strong>Macular hole (MH) diameters ranged from 711.2 ± 251.9 µm to 1299.9 ± 333.0 µm, with MH closure achieved in all patients. RPE-BM complex thickness decreased by 4.17 µm at 6 months and 4.34 µm at 1 year, showing significant differences from preoperative measurements (29.88 ± 4.99 µm; 6 months: 95% confidence interval [CI], 1.62-6.71, P = 0.0018; 1 year: 95% CI, 2.03-6.65 µm, P = 0.00044). The decrease was significantly greater in the edema-positive group (95% CI, -8.33 to -0.82, P = 0.020). Furthermore, the rates of ellipsoid zone (EZ) recovery, alignment of neurosensory layers (ANL), and graft reperfusion were lower in the edema-positive group (EZ, P = 0.017; ANL, P = 0.0098; reperfusion, P = 0.039).</p><p><strong>Conclusions: </strong>After ART, RPE-BM complex thickness decreases, particularly in cases with postoperative edema, suggesting a potential relationship between RPE function and postoperative outcomes, highlighting the importance of monitoring RPE-BM complex thickness after surgery.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465669","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":"PAX6-WNK2 Axis Governs Corneal Epithelial Homeostasis.","authors":"Liqiong Zhu, Chaoqun Chen, Siqi Wu, Huizhen Guo, Lingyu Li, Li Wang, Dongmei Liu, Yu Zhan, Xinyue Du, Jiafeng Liu, Jieying Tan, Ying Huang, Kunlun Mo, Xihong Lan, Hong Ouyang, Jin Yuan, Xiangjun Chen, Jianping Ji","doi":"10.1167/iovs.65.12.40","DOIUrl":"10.1167/iovs.65.12.40","url":null,"abstract":"<p><strong>Purpose: </strong>Limbal stem/progenitor cells (LSCs) continuously proliferate and differentiate to replenish the corneal epithelium and play a vital role in corneal function and normal vision. A previous study revealed that paired box 6 (PAX6) is a master transcription factor involved in determining the fate of corneal epithelial cells (CECs). However, the molecular events downstream of PAX6 remain largely unknown. In this study, we aimed to clarify the regulation network of PAX6 in driving CEC differentiation.</p><p><strong>Methods: </strong>An air-liquid culture system was used to differentiate LSCs into mature CECs. Specific targeting PAX6 short-hairpin RNAs were used to knock down PAX6 in LSC. RNA sequencing (RNA-seq) was used to analyze shPAX6-transfected CECs and CEC differentiation-associated genes to identify the potential downstream targets of PAX6. RNA-seq analysis, quantitative real-time PCR, and immunofluorescence staining were performed to clarify the function of WNK lysine deficient protein kinase 2 (WNK2), a downstream target of PAX6, and its relationship with corneal diseases.</p><p><strong>Results: </strong>WNK2 expression increased during CEC differentiation and decreased upon PAX6 depletion. The distribution of WNK2 was specifically limited to the central corneal epithelium and suprabasal layer of the limbus. Knockdown of WNK2 impaired the expression of CEC-specific markers (KRT12, ALDH3A1, and CLU), disrupted the corneal differentiation process, and activated the terms of keratinization, inflammation, and cell proliferation, consistent with PAX6-depleted CEC and published microbial keratitis. Thus, aberrant expression of WNK2 was linked to corneal ulcers.</p><p><strong>Conclusions: </strong>As a downstream target of PAX6, WNK2 plays an essential role in corneal epithelial cell differentiation and maintenance of corneal homeostasis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500609","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":"Tissue-Specific Immune Transcriptional Signatures in the Bordering Tissues of the Mouse Retina and Brain.","authors":"Fazeleh Etebar, Paul Whatmore, Damien G Harkin, Samantha J Dando","doi":"10.1167/iovs.65.12.42","DOIUrl":"10.1167/iovs.65.12.42","url":null,"abstract":"<p><strong>Purpose: </strong>Bordering the central nervous system (CNS) parenchyma are the choroid (underlying the retina) and the leptomeninges (the inner layers of the meninges enveloping the brain). Although near the neural parenchyma, the choroid and leptomeninges are external to the immune privileged environment of the retina and brain and thus are distinct immune compartments. This study aimed to characterize the transcriptomic signatures of immune cells within the choroid and leptomeninges bordering the healthy adult mouse CNS.</p><p><strong>Methods: </strong>Eyes and brains were obtained from 7-week-old C57Bl/6J mice. Choroid and leptomeninges were processed for isolation of CD45+ immune cells and single cell RNA-sequencing. Additionally, single cell RNA-sequencing was performed on immune cells isolated from choroid obtained from human donor eye tissue. Immunostaining and confocal microscopy of wholemount tissue were used to validate selected immune cell populations in situ.</p><p><strong>Results: </strong>A total of 3606 cells were sequenced from mouse tissues, including 2125 CD45+ cells from choroid and 1481 CD45+ cells from leptomeninges. Clustering and differential gene expression analysis revealed heterogeneous subtypes of monocytes/macrophages, dendritic cells, T cells, and B cells. Whereas some clusters were common to both choroid and leptomeninges, others exhibited tissue-specific gene expression profiles and potential functional specializations. Analysis of 6501 CD45+ cells sequenced from human choroid identified similar immune cell populations to mouse choroid.</p><p><strong>Conclusions: </strong>This study provides a detailed characterization of the molecular signatures of immune cells within the vascular connective tissues bordering the healthy retina and brain, and their potential roles in immune protection.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500612","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":"Ganglion Cell Complex Thickness and Visual Function in Chronic Leber Hereditary Optic Neuropathy.","authors":"Johan Hedström, Maria Nilsson, Martin Engvall, Pete A Williams, Abinaya Priya Venkataraman","doi":"10.1167/iovs.65.12.4","DOIUrl":"10.1167/iovs.65.12.4","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the correlation between the macular ganglion cell complex (GCC) thickness measured with manually corrected segmentation and visual function in individuals with chronic Leber hereditary optic neuropathy (LHON).</p><p><strong>Methods: </strong>Twenty-six chronic LHON subjects (60% treated with idebenone or Q10) from the Swedish LHON registry were enrolled. Best-corrected visual acuity (BCVA), visual field tests, and optical coherence tomography (OCT) were performed. Visual field was evaluated with the Haag-Streit Octopus 900 with the Esterman test and a custom 30° test. Canon OCT-HS100 scans were exported to the Iowa Reference Algorithm. GCC thickness was obtained after the segmentation was corrected manually in nine macular sectors.</p><p><strong>Results: </strong>The GCC thickness was overestimated by 16 to 30 µm in different macular sectors with the automated segmentation compared with the corrected (P < 0.001). GCC thickness in all sectors showed significant correlation with all functional parameters. The strongest correlation was seen for the external temporal sector (BCVA: r = 0.604, P < 0.001; mean defect: r = 0.457, P = 0.001; Esterman score: r = 0.421, P = 0.003). No differences were seen between treated and untreated subjects with regard to GCC and visual field scores (P > 0.05), but BCVA was better among treated subjects (P = 0.017).</p><p><strong>Conclusions: </strong>The corrected GCC thickness showed correlation with visual function in chronic LHON subjects. The frequently occurring segmentation errors in OCT measurements related to chronic LHON can potentially be misleading in monitoring of disease progression and in evaluating the treatment effects. Precise measurements of GCC could serve as a sensitive tool to monitor structural changes in LHON. We therefore emphasize the importance of careful evaluation of the accuracy of OCT segmentation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457923/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371856","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}