Investigative ophthalmology & visual science最新文献

{"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":"65 12","pages":"7"},"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":"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":"65 12","pages":"25"},"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":"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":"65 12","pages":"23"},"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":"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":"65 12","pages":"40"},"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":"65 12","pages":"42"},"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":"Association of Ambient Air Pollution Exposure With Incident Glaucoma: 12-Year Evidence From the UK Biobank Cohort.","authors":"Zihan Sun, Kelsey V Stuart, Robert N Luben, Amy L Auld, Nicholas G Strouthidis, Peng T Khaw, Hari Jayaram, Anthony P Khawaja, Paul J Foster","doi":"10.1167/iovs.65.12.22","DOIUrl":"https://doi.org/10.1167/iovs.65.12.22","url":null,"abstract":"<p><strong>Purpose: </strong>Glaucoma is the leading cause of irreversible blindness worldwide. Despite growing concerns about air quality and its impact on ocular health, there remains a knowledge gap regarding the long-term association between air pollution and glaucoma risk. This study investigates the relationship between exposure to ambient air pollution and incidence of glaucoma.</p><p><strong>Methods: </strong>In this prospective study, we used land use regression models to estimate levels of various air pollutants, including fine particulate matter (PM2.5), PM2.5 absorbance, PM2.5-10, PM10, nitrogen dioxide (NO2), and nitrogen oxides (NOx). Incidents of glaucoma were ascertained through routinely collected hospital admission records. Multivariate Cox proportional hazards models were used to examine the associations between air pollution exposure and glaucoma incidence, adjusting for potential confounding sociodemographic, physical, and lifestyle factors.</p><p><strong>Results: </strong>Data from 481,113 participants were included. Over a median follow-up of 12.8 years, 9224 incident cases of glaucoma were identified. In the maximally adjusted model, per interquartile range increase in PM2.5 was associated with a 3% greater risk of developing glaucoma (hazard ratio [HR] = 1.03, 95% confidence interval [CI] = 1.00 to 1.06, P = 0.048). Participants in the highest quartile had a 10% increased risk of developing glaucoma compared to those in the lowest quartile (HR = 1.10, 95% CI = 1.03 to 1.17, P = 0.005).</p><p><strong>Conclusions: </strong>Higher levels of exposure to ambient air pollutants, particularly PM2.5, are associated with an increased risk of developing glaucoma. These results highlight the potential public health impact of ambient air pollution on glaucoma risk and underscore the urgent need for further research into targeted environmental interventions in this domain.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"22"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142465679","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":"Differential Localization and Functional Roles of mGluR6 Paralogs in Zebrafish Retina.","authors":"Marion Haug, Sara A Haddad-Velioglu, Manuela Berger, Anja Enz, Jingjing Zang, Stephan C F Neuhauss","doi":"10.1167/iovs.65.12.44","DOIUrl":"10.1167/iovs.65.12.44","url":null,"abstract":"<p><strong>Purpose: </strong>To define the location of mglur6 paralogs in the outer zebrafish retina and delineate their contribution to retina light responses across the visual spectrum.</p><p><strong>Methods: </strong>In situ hybridization and immunolocalization with custom-made antibodies were used to localize mglur6 transcripts, proteins, and additional components of the mGluR6 signaling complex. Gene editing was used to generate knockout mutants that were analyzed with white light and spectral electroretinography.</p><p><strong>Results: </strong>Both mglur6 paralogs colocalized with known downstream pathway genes, such as trpm1a, nyctalopin, and gnaoβ. All rod photoreceptors contacted mGluR6-positive cells, while cone connectivity presented a more complex situation with no red cones and only a few UV and blue-sensitive cones connecting to mGluR6a-positive bipolar cells. All cone subtypes contacted mGluR6b-positive cells with markedly fewer red-sensitive cones. Retinas of knockout animals displayed no morphologic alterations. While ERG responses were unaffected in mglur6a knockout animals, mglur6b mutants displayed decreased responses over all spectral wavelengths.</p><p><strong>Conclusions: </strong>We demonstrated that mGlurR6 signalplex components are similar in the zebrafish and the mammalian retina. Despite mglur6b knockout animals having significantly impaired ERG b-wave responses, a residual b-wave persists, even in double knockouts, suggesting additional pathway components yet to be identified.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"44"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545489","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":"65 12","pages":"4"},"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}

{"title":"Longitudinal Imaging of the Foveal Cone Mosaic in CNGA3-Associated Achromatopsia.","authors":"Mohamed Katta, Michalis Georgiou, Navjit Singh, Angelos Kalitzeos, Alfredo Dubra, Joseph Carroll, Michel Michaelides","doi":"10.1167/iovs.65.12.6","DOIUrl":"10.1167/iovs.65.12.6","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to assess the natural history of the foveal cone mosaic in CNGA3-associated achromatopsia (ACHM).</p><p><strong>Methods: </strong>Thirteen eyes from 10 genetically confirmed patients underwent longitudinal imaging with optical coherence tomography (OCT) and non-confocal split detection adaptive optics scanning light ophthalmoscopy (AOSLO). OCT scans assessed outer nuclear layer (ONL) thickness, foveal ellipsoid zone (EZ) disruption, and foveal hypoplasia. AOSLO images were analyzed to calculate peak foveal cone density (PCD) and mean inter-cell distance (ICD) between cones. Mixed effects models were used to analyze the rate of annual change of PCD and ICD.</p><p><strong>Results: </strong>Mean (±SD) age at visits was 29 ± 10 years, with a follow-up of 2.6 ± 1 years. There was no change in ONL thickness, degree of EZ disruption, or foveal hypoplasia over the follow-up period. We also observed a stable foveal cone mosaic using AOSLO imaging, with no significant change in PCD or ICD. Mean PCD was 15,346 cones/mm² at the mean age of 29 years old (cf. 64,000-324,000 cones/mm² in previously reported healthy controls), with a mean rate of change of -117.79 cones/mm² (0.8%) per year, P = 0.130. Mean ICD at the mean age was 13.82 µm, with a rate of change of 0.17 µm per year, P = 0.83.</p><p><strong>Conclusions: </strong>CNGA3-associated ACHM displays stable foveal cone structure over time with a similar rate of change to CNGB3-associated ACHM (2% decline per year). The stable PCD, small cohort, and large variability within the cohort means significant age associations were not detected.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"6"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11460564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371858","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":"ALKBH5 Regulates Corneal Neovascularization by Mediating FOXM1 M6A Demethylation.","authors":"Wei Wang, Hua Li, Yiyong Qian, Min Li, Manli Deng, Dexi Bi, Jun Zou","doi":"10.1167/iovs.65.12.34","DOIUrl":"10.1167/iovs.65.12.34","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to explore the regulatory role and potential mechanisms of ALKBH5-mediated N6-methyladenosine (m6A) demethylation modification in corneal neovascularization (CNV).</p><p><strong>Methods: </strong>A mouse CNV model was established through corneal alkali burns. Total m6A levels were measured using an m6A RNA methylation quantification kit. The mRNA expression of candidate m6A-related enzymes was quantified by quantitative RT-PCR. Small interfering RNA targeting ALKBH5 was injected subconjunctivally into alkali-burned mice. The CNV area, corneal epithelial thickness, and pathological changes were evaluated. Protein expression was detected by western blot and immunofluorescence. Human umbilical vein endothelial cells (HUVECs) were treated with IL-6. Plasmid transfection knocked down ALKBH5 or overexpressed FOXM1 in IL-6-induced HUVECs. The assays of CCK8, wound healing, and tube formation evaluated the cell proliferation, migration, and tube formation abilities, respectively. The dual-luciferase assay examined the binding between ALKBH5 and FOXM1. Methylated RNA immunoprecipitation-qPCR detected the m6A levels of FOXM1.</p><p><strong>Results: </strong>Significant CNV was observed on the seventh day. Total m6A levels were reduced, and ALKBH5 expression was increased in CNV corneas and IL-6-induced HUVECs. ALKBH5 knockdown alleviated corneal neovascularization and inflammation and countered IL-6-induced promotion of cell proliferation, migration, and tube formation in HUVECs. ALKBH5 depletion increased m6A levels and decreased VEGFA and CD31 expression both in vivo and in vitro. This knockdown in HUVECs elevated m6A levels on FOXM1 mRNA while reducing its mRNA and protein expression. Notably, FOXM1 overexpression can reverse ALKBH5 depletion effects.</p><p><strong>Conclusions: </strong>ALKBH5 modulates FOXM1 m6A demethylation, influencing CNV progression and highlighting its potential as a therapeutic target.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 12","pages":"34"},"PeriodicalIF":5.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142500604","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}