Investigative ophthalmology & visual science最新文献

{"title":"Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies.","authors":"Melissa A Calton, Roxanne H Croze, Christian Burns, Ghezal Beliakoff, Tandis Vazin, Paul Szymanski, Christopher Schmitt, Austin Klein, Meredith Leong, Melissa Quezada, Jenny Holt, Gabe Bolender, Katherine Barglow, Devi Khoday, Thomas Mason, Katherine Delaria, Mohammad Hassanipour, Melissa Kotterman, Arshad M Khanani, David Schaffer, Peter Francis, David Kirn","doi":"10.1167/iovs.65.14.1","DOIUrl":"10.1167/iovs.65.14.1","url":null,"abstract":"<p><strong>Purpose: </strong>Intravitreal delivery of therapeutic transgenes to the retina via engineered viral vectors can provide sustained local concentrations of therapeutic proteins and thus potentially reduce the treatment burden and improve long-term vision outcomes for patients with neovascular (wet) age-related macular degeneration (AMD), diabetic macular edema (DME), and diabetic retinopathy.</p><p><strong>Methods: </strong>We performed directed evolution in nonhuman primates (NHP) to invent an adeno-associated viral (AAV) variant (R100) with the capacity to cross vitreoretinal barriers and transduce all regions and layers of the retina following intravitreal injection. We then engineered 4D-150, an R100-based genetic medicine carrying 2 therapeutic transgenes: a codon-optimized sequence encoding aflibercept, a recombinant protein that inhibits VEGF-A, VEGF-B, and PlGF, and a microRNA sequence that inhibits expression of VEGF-C. Transduction, transgene expression, and biological activity were characterized in human retinal cells in vitro and in NHPs.</p><p><strong>Results: </strong>R100 demonstrated superior retinal cell transduction in vitro and in vivo compared to AAV2, a commonly used wild-type AAV serotype in retinal gene therapies. Transduction of human retinal pigment epithelial cells in vitro by 4D-150 resulted in dose-dependent transgene expression and corresponding reductions in VEGF-A and VEGF-C. Intravitreal administration of 4D-150 to NHPs was well tolerated and led to robust retinal expression of both transgenes. In a primate model of laser-induced choroidal neovascularization, 4D-150 completely prevented clinically relevant angiogenic lesions at all tested doses.</p><p><strong>Conclusions: </strong>These findings support further development of 4D-150. Clinical trials are underway to establish the safety and efficacy of 4D-150 in individuals with wet AMD and DME.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"1"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11614000/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768123","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":"A Sex-Dependent Cannabinoid CB1 Receptor Role in Circadian Tearing of the Mouse.","authors":"Natalia Murataeva, Kyle Yust, Sam Mattox, Wenwen Du, Alex Straiker","doi":"10.1167/iovs.65.14.10","DOIUrl":"10.1167/iovs.65.14.10","url":null,"abstract":"<p><strong>Purpose: </strong>We have shown that cannabinoid CB1 receptors regulate both salivation and tearing, but for tearing, this regulation is sex dependent with opposing effects by sex. We investigated a potential interplay of circadian and cannabinoid regulation of tearing.</p><p><strong>Methods: </strong>We measured cannabinoid and circadian regulation of tearing in CD1 strain mice as well as CB1 receptor protein expression using immunohistochemistry.</p><p><strong>Results: </strong>We now report that CD1 strain mice have a circadian variation in basal tearing, differing by sex in terms of phase and amplitude. The amplitude of circadian variation in females is substantially dampened relative to males. Male CB1 receptor knockout mice do not differ from strain controls, but in female CB1 knockouts, the amplitude is enhanced and resembles that of WT males. This increased tearing is mimicked by the CB1 antagonist SR141716 (4 mg/kg, intraperitoneally [IP]), suggesting that tonic CB1 activation dampens female circadian tearing. Consistent with this, the cannabinoid receptor agonist CP55940 (0.5 mg/kg, IP) decreases tearing during the rest phase but increases tearing during the active phase in females. CB1 protein expression also differs by sex. While both males and females have CB1 receptors in parasympathetic inputs to the lacrimal gland, in female lacrimal glands, CB1 is also detected in myoepithethial cells.</p><p><strong>Conclusions: </strong>Mice have a sex-dependent circadian cycle of tearing. The endogenous cannabinoid signaling system appears to mediate some circadian effects, albeit in a sex-dependent manner and via distinct cellular targets.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"10"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11622162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142769113","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":"Itaconate Ameliorates Experimental Autoimmune Uveitis by Modulating Teff/Treg Cell Imbalance Via the DNAJA1/CDC45 Axis.","authors":"Qi Jiang, Zhaohuai Li, Yao Huang, Zhaohao Huang, Junjie Chen, Xiuxing Liu, Chun Zhang, Chenyang Gu, Tianfu Wang, He Li, Yingqi Li, Wenru Su","doi":"10.1167/iovs.65.14.23","DOIUrl":"10.1167/iovs.65.14.23","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to elucidate the effect of itaconate (ITA) on experimental autoimmune uveitis (EAU), to explore its potential mechanism, and to identify potential therapeutic targets.</p><p><strong>Methods: </strong>We established an animal model of EAU by constructing an immune map of mice treated with ITA and exploring the therapeutic mechanism of ITA by single-cell RNA sequencing and flow cytometry.</p><p><strong>Results: </strong>ITA mitigated ocular inflammation associated with EAU and reversed the pathogenic differentiation linked to Th17 induction by EAU, along with the reactive oxygen species (ROS) and oxidative stress pathways. Subsequent to ITA intervention, the downregulated differentially expressed genes in the T-cell subset primarily centered around the heat shock protein (HSP) family. Activation of HSPs reversed the anti-inflammatory effects of ITA in EAU mice. ITA decreased ROS levels and HSP expression in CD4+ T cells, with DnaJ heat shock protein family (HSP40) member A1 (DNAJA1) exhibiting the most notable alterations among the HSPs. ITA suppressed the expression of DNAJA1/cell division cycle protein 45 (CDC45), thereby disrupting the pathogenic division cycle of CD4+ T cells and reducing their proliferation. Inhibiting DNAJA1 also held promise for modulating the Th17/Treg imbalance. Notably, ITA curtailed the expansion of CD4+ T cells in uveitis patients.</p><p><strong>Conclusions: </strong>Our research delved into the potential therapeutic mechanisms underlying ITA therapy in EAU, offering fresh perspectives on its utility in the treatment of autoimmune conditions. DNAJA1 emerges as a promising candidate for targeted therapeutic interventions in uveitis.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"23"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11636664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806785","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":"Sphingolipid Levels and Processing of the Retinyl Chromophore in the Retina of a Mouse Model of Niemann-Pick Disease.","authors":"Bushra Rahman, David M G Anderson, Chunhe Chen, Jian Liu, Lukasz G Migas, Raf Van de Plas, Kevin L Schey, Masahiro Kono, Jie Fan, Yiannis Koutalos","doi":"10.1167/iovs.65.14.24","DOIUrl":"10.1167/iovs.65.14.24","url":null,"abstract":"<p><strong>Purpose: </strong>Mutations in the gene that encodes the enzyme acid sphingomyelinase (ASMase) are associated with Niemann-Pick disease, a lysosomal storage disorder. Mice that lack ASMase (ASMase-/-) exhibit age-related retinal degeneration and large increases in accumulation of lipofuscin in the retinal pigment epithelium (RPE). We examined which lipid species accumulate in the retina and the RPE of ASMase-/- mice and whether the retinal degeneration is associated with impaired photoreceptor metabolism and retinyl chromophore processing.</p><p><strong>Methods: </strong>NADPH availability and all-trans retinol formation after rhodopsin bleaching were measured in isolated single rod photoreceptors with fluorescence imaging; sphingolipid levels in retinas and RPEs were measured with LC/MS; relative abundances of different lipid species in different retinal layers were measured with MALDI imaging mass spectrometry.</p><p><strong>Results: </strong>There was no detectable difference in the kinetics of all-trans retinol formation or the NADPH-generating capacity between ASMase-/- and wild-type mice. Sphingomyelin levels were much higher in the retinas and RPEs of ASMase-/- animals compared to wild type, but there were no significant differences for ceramides. There was a large increase in the abundance of bis(monoacylglycero)phosphates (BMPs) in ASMase-/- mice, indicative of lysosomal dysfunction, but no substantial changes were detected for the bis-retinoid A2E.</p><p><strong>Conclusions: </strong>Lysosomal dysfunction and retinal degeneration in ASMase-/- mice are not associated with defects in rod photoreceptor metabolism that affect all-trans retinol formation and availability of NADPH. Lysosomal dysfunction in ASMase-/- mice is not associated with bis-retinoid A2E accumulation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"24"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11640910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806810","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":"Onset and Progression of Disease in Nonhuman Primates With PDE6C Cone Disorder.","authors":"Monica Ardon, Lily Nguyen, Rui Chen, Jeffrey Rogers, Tim Stout, Sara Thomasy, Ala Moshiri","doi":"10.1167/iovs.65.14.16","DOIUrl":"10.1167/iovs.65.14.16","url":null,"abstract":"<p><strong>Purpose: </strong>The California National Primate Research Center contains a colony of rhesus macaques with a homozygous missense mutation in PDE6C (R565Q) which causes a cone disorder similar to PDE6C achromatopsia in humans. The purposes of this study are to characterize the phenotype in PDE6C macaques in detail to determine the onset of the cone phenotype, the degree to which the phenotype progresses, if heterozygote animals have an intermediate phenotype, and if rod photoreceptor function declines over time.</p><p><strong>Methods: </strong>We analyzed spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and electroretinography (ERG) data from 102 eyes of 51 macaques (aged 0.25 to 16 years). Measurements of retinal layers as well as cone and rod function over time were quantitatively compared.</p><p><strong>Results: </strong>Homozygotes as young as 3 months postnatal showed absent cone responses on electroretinogram. Infant homozygotes had reduced foveal outer nuclear layer (ONL) thickness compared with wildtype infants (P < 0.0001). Over 4 years of study, no consistent changes in retinal layer thicknesses were found within 5 adult homozygotes. However, comparisons between infants and adults revealed reductions in foveal ONL thickness suggesting that cone cells slowly degenerate as homozygotes age. The oldest homozygote (11 years) had reduced rod responses. Heterozygotes could not be distinguished from wildtypes in any parameters.</p><p><strong>Conclusions: </strong>These data suggest that, like humans, macaque PDE6C heterozygotes are normal, and homozygote primates have absent cone function and reduced foveal ONL thickness from infancy. Cone photoreceptors probably degenerate over time and macular atrophy can occur. Rod photoreceptor function may wane in late stages.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"16"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785632","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":"Endoplasmic Reticulum Stress Induces ROS Production and Activates NLRP3 Inflammasome Via the PERK-CHOP Signaling Pathway in Dry Eye Disease.","authors":"Zhiwei Zha, Decheng Xiao, Zihao Liu, Fangli Peng, Xunjie Shang, Zhenzhen Sun, Yang Liu, Wei Chen","doi":"10.1167/iovs.65.14.34","DOIUrl":"10.1167/iovs.65.14.34","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the potential roles of endoplasmic reticulum (ER) stress in the development of dry eye disease (DED).</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) data from the Gene Expression Omnibus (GEO) database, derived from corneal tissues of a dry eye mouse model, was processed using the Seurat R program. The results were validated using a scopolamine-induced dry eye mouse model and a hyperosmotic-induced cell model involving primary human corneal epithelial cells (HCECs) and immortalized human corneal epithelial (HCE-2) cells. The HCE-2 cells were treated with 4-phenylbutyric acid (4-PBA) or tunicamycin (TM) to modulate ER stress. TXNIP and PERK knockdown were performed by siRNA transfection. Immunofluorescence, Western blotting, and real-time PCR were used to assess oxidative stress, ER stress, unfolded protein response (UPR) marker proteins, and TXNIP/NLRP3 axis activation.</p><p><strong>Results: </strong>The analysis of scRNAseq data shows an increase in the ER stress marker GRP78, and the activation of the PERK-CHOP of UPR in DED mouse. These findings were confirmed both in vivo and in vitro. Additionally, HCE-2 cells treated with 4-PBA or TM showed significant effects on the production of reactive oxygen species (ROS) and the activation of the TXNIP/NLRP3-IL1β signaling pathway. Furthermore, siRNA knockdown of PERK or TXNIP, which alleviated the TXNIP/NLRP3-IL1β signaling axis, showed protective effects on HCECs.</p><p><strong>Conclusions: </strong>This study explores the role of ER stress-induced oxidative stress and NLRP3-IL-1β mediated inflammation in DED, and highlights the therapeutic potential of PERK-CHOP axis and TXNIP in the treatment of DED.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"34"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854220","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":"Clinical and Imaging Characteristics of PRPH2 Retinopathies in a Longitudinal Cohort and Diagnostic Implications.","authors":"Johanna M Seddon, Dikha De, Laura Grunenkovaite, Daniela Ferrara","doi":"10.1167/iovs.65.14.31","DOIUrl":"10.1167/iovs.65.14.31","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to define genotypic-phenotypic correlations related to PRPH2-associated retinopathies in an observational longitudinal cohort and to improve diagnostic accuracy.</p><p><strong>Methods: </strong>Individuals with PRPH2 variants were identified by genetic sequencing of 263 individuals (including 59 families). Ocular examinations with multimodal imaging were evaluated.</p><p><strong>Results: </strong>Two pathogenic/likely pathogenic PRPH2 variants were identified in 22 individuals with retinopathies, low genetic susceptibility to age-related macular degeneration (AMD) and younger age of onset. The mean follow-up was 14 years. One family and 4 independent cases (n = 7) were heterozygous for the variant rs121918563 L185P (p.Leu185Pro). The individuals developed retinopathy compatible with autosomal dominant pattern dystrophy (PD), including adult-onset vitelliform macular dystrophy and butterfly macular dystrophy in their fourth to fifth decades of life, evolving to retinal pigment epithelial (RPE) irregularities and central macular atrophy 20 years later. Two families and an independent case (n = 15) had the rs281865373 splice-site variant c.828+3A>T (IVS2+3A>T) presenting as retinal flecks consistent with adult-onset fundus flavimaculatus with macular dystrophy and diffuse RPE atrophy consistent with central areolar chorioretinal dystrophy (CACD) in the fifth decade of life progressing to extensive atrophy in the sixth to eighth decades. The L185P variant was associated with better visual acuity (VA) during follow-up versus c.828+3A>T variant. Some individuals were initially misdiagnosed with geographic atrophy secondary to AMD.</p><p><strong>Conclusions: </strong>Individuals with the L185P variant had less severe disease with clinical manifestation typical of PD and better VA. More advanced disease with CACD and worse VA were associated with the c.828+3A>T variant. Results contribute to knowledge about genotypic-phenotypic associations of PRPH2 retinopathies and inform clinical and therapeutic end points.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"31"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846574","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":"Changes in Waveguiding Cone Photoreceptors and Color Vision in Patients With Diabetes Mellitus.","authors":"Megan Vaughan, Nicole Tay, Angelos Kalitzeos, Thomas Kane, Nav Singh, Adrian Zheng, Mira Dixit, Bishwanath Pal, Ranjan Rajendram, Konstantinos Balaskas, Mari Pilar Martin Gutierrez, Jose Carlo Artiaga, Georgios Koutsocheras, Khadra Adan, Marisa Rodriguez-Carmona, John L Barbur, Michel Michaelides, Emily J Patterson","doi":"10.1167/iovs.65.14.28","DOIUrl":"10.1167/iovs.65.14.28","url":null,"abstract":"<p><strong>Purpose: </strong>Although it is well known that photoreceptor damage and color vision loss occur in patients with diabetic retinopathy (DR), the relationship between structural and functional changes in diabetes mellitus (DM) remains unclear. Using highly sensitive measures of photoreceptor structure and function, we aim to determine whether early loss of color sensitivity in DM is also accompanied by decreased cone density.</p><p><strong>Methods: </strong>Monocular data from 26 patients with DM and 25 healthy controls were examined to assess cone photoreceptor metrics, using confocal adaptive optics scanning light ophthalmoscopy, and red/green (RG) and yellow/blue (YB) color vision thresholds, using the Colour Assessment and Diagnosis test.</p><p><strong>Results: </strong>Both RG and YB thresholds were significantly greater in patients with DM than in the healthy controls (RG and YB = P < 0.001), and there were statistically significant differences between the 2 groups in confocal cone density at 1 degree (P = 0.024), and intercell regularity at both 1 (P = 0.013) and 2 degrees (P = 0.012). In patients with DM, cone density was inversely correlated with YB (at 0.5, 1 and 2 degrees, all P values < 0.041), but not for RG color vision thresholds.</p><p><strong>Conclusions: </strong>This is the first study to investigate the relationship between cone metrics and color vision in patients with DM. The results reveal a significant inverse relationship between confocal cone density and color vision thresholds at the locations assessed within the foveal region. These findings represent a significant advancement in oculomics research.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"28"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818228","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 Metabolomics With Incidence of Age-Related Macular Degeneration: The UK Biobank Study.","authors":"Jun Yu, Yuzhou Zhang, Mary Ho, Xiu Juan Zhang, Ka Wai Kam, Alvin L Young, Chi Pui Pang, Clement C Tham, Jason C Yam, Li Jia Chen","doi":"10.1167/iovs.65.14.43","DOIUrl":"10.1167/iovs.65.14.43","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to identify serum metabolites associated with age-related macular degeneration (AMD) incidence and investigate whether metabolite profiles enhance AMD risk prediction.</p><p><strong>Methods: </strong>In a prospective cohort study involving 240,317 UK Biobank participants, we assessed the associations of 168 metabolites with AMD incidence using Cox hazards models. Principal component analysis (PCA) captured 90% of the variance in metabolites. These principal components (PCs) were added to the Cox models, with the first PC selected to evaluate model performance using receiver operating characteristic (ROC) curves.</p><p><strong>Results: </strong>During a median follow-up of 13.69 years, 5199 (2.16%) participants developed AMD. After accounting for demographic, lifestyle, multimorbidity, socioeconomic factors, and genetic predispositions to AMD, 42 metabolites were associated with AMD incidence. Very-low-density lipoprotein (VLDL)-related particles, low-density lipoprotein (LDL)-related particles, three additional lipids particles, and albumin were associated with decreased AMD incidence, whereas glucose increased the risk of AMD incidence. Compared to those in the lowest quartile, individuals in the highest quartile of protective metabolite scores exhibited lower risk of AMD incidence (hazard ratio [HR] = 0.869, 95% confidence interval [CI] = 0.803-0.940, false discovery rate [FDR]-adjusted P = 1.44 × 10-3). However, the AMD-associated metabolites did not enhance predictive performance (both areas under the curve [AUC] = 0.776).</p><p><strong>Conclusions: </strong>Our findings reveal significant associations between specific metabolites and AMD incidence, highlighting the roles of lipoprotein subclasses, cholesterol subtypes, apolipoproteins, glucose, and albumin. Although metabolomics did not improve risk prediction, certain biomarkers may serve as promising therapeutic targets.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"43"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909679","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":"Effects of Physical Activity and Inactivity on Microvasculature in Children: The Hong Kong Children Eye Study.","authors":"Xiu Juan Zhang, Vincent L Yuen, Yuzhou Zhang, Ka Wai Kam, Jason Wong, Fang Yao Tang, Alvin Young, Patrick Ip, Li Jia Chen, Tien Y Wong, Chi Pui Pang, Clement C Tham, Carol Y Cheung, Jason C Yam","doi":"10.1167/iovs.65.14.7","DOIUrl":"10.1167/iovs.65.14.7","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the effects of physical activity and inactivity on the microvasculature in children, as measured from retinal photographs.</p><p><strong>Methods: </strong>All participants were from the Hong Kong Children Eye Study, a population-based cross-sectional study of children aged 6 to 8 years. They received comprehensive ophthalmic examinations and retinal photography. Their demographics and involvement in physical activity and inactivity were obtained from validated questionnaires. A validated Deep Learning System was used to measure, from retinal photographs, central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE).</p><p><strong>Results: </strong>In the final analysis of 11,959 participants, 6244 (52.2%) were boys and the mean age was 7.55 (1.05) years. Increased ratio of physical activity to inactivity was associated with wider CRAE (β = 1.033, P = 0.007) and narrower CRVE (β = -2.079, P < 0.001). In the subgroup analysis of boys, increased ratio of physical activity to inactivity was associated with wider CRAE (β = 1.364, P = 0.013) and narrower CRVE (β = -2.563, P = 0.001). The subgroup analysis of girls also showed increased ratio of physical activity to inactivity was associated with narrower CRVE (β = -1.759, P = 0.020), but not CRAE.</p><p><strong>Conclusions: </strong>Increased activity in children is associated with healthier microvasculature, as shown in the retina. Our study contributes to the growing evidence that physical activity positively influences vascular health from a young age. Therefore, this study also underscores the potential of using the retinal vasculature as a biomarker of cardiovascular health.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"65 14","pages":"7"},"PeriodicalIF":5.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11620007/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142768893","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}