Investigative ophthalmology & visual science最新文献

{"title":"AAV Gene Augmentation Therapy Rescues the Phenotype in the RDH5-/- Cat Model of Fundus Albipunctatus.","authors":"Laura M Ford, Kelian Sun, Laurence M Occelli, Mary E Enfield, Anahita Daruwalla, Ryan F Boyd, Philip D Kiser, Simon M Petersen-Jones","doi":"10.1167/iovs.67.12.45","DOIUrl":"https://doi.org/10.1167/iovs.67.12.45","url":null,"abstract":"<p><strong>Purpose: </strong>Retinol dehydrogenase 5 (RDH5) catalyzes the final oxidation for visual pigment regeneration of 11-cis-retinal as part of the visual cycle in the retinal pigment epithelium (RPE). In humans, RDH5 mutations cause fundus albipunctatus characterized by night blindness, accumulation of white-yellowish fundus spots, and, in a subset of patients, macular degeneration. Currently, there is an unmet need for therapies for patients with RDH5 mutations. Using a large-animal cat model of RDH5-associated disease (RDH5-/-), this study aimed to meet these needs through development of a gene augmentation therapy able to rescue RDH5-associated retinopathies.</p><p><strong>Methods: </strong>An adeno-associated virus serotype 2 with triple capsid mutations vector packaged with feline RDH5 cDNA (AAV-VMD2-fRDH5) was subretinally injected into 12 RDH5-/- cats. To assess expression and the impact of treatment on retinal function and structure, immunohistochemistry, high-performance liquid chromatography, rod and cone electroretinograms, spectral-domain optical coherence tomography, and semi-thin resin-embedded sectioning were performed.</p><p><strong>Results: </strong>The expression of the RDH5 transgene improved rod and cone photoreceptor functional recovery following light exposure and shows promise in slowing/halting area centralis (analogous to the human macula) degeneration.</p><p><strong>Conclusions: </strong>This gene augmentation therapy is a promising approach for the treatment of RDH5-associated retinopathies.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"45"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238357","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 Vessel Traits and the Development of Balance Impairment: The Canadian Longitudinal Study on Aging.","authors":"Anas Khoja, Roshan A Welikala, Sarah Barman, Christopher G Owen, Alicja R Rudnicka, Mohan Rakesh, Marie-Hélène Roy-Gagnon, David Maberley, Marie-Jeanne Kergoat, Nicole Paquet, Alyssa Grant, Ellen E Freeman","doi":"10.1167/iovs.67.12.6","DOIUrl":"10.1167/iovs.67.12.6","url":null,"abstract":"<p><strong>Purpose: </strong>The association between retinal microvascular traits and balance has not been studied. Our goal was to assess whether retinal vessel width, area, and tortuosity are associated with the development of balance impairment.</p><p><strong>Methods: </strong>Baseline and 3-year follow-up data from the Canadian Longitudinal Study on Aging Comprehensive Cohort were analyzed. Adults aged 45 to 85 years who successfully passed a one-legged balance test at baseline were included (n = 12,929). Retinal arteriolar and venular width, area, and tortuosity were quantified using the Quantitative Analysis of Retinal Vessel Topology and Size algorithm. Multivariable logistic regression models examined the longitudinal associations between retinal vessel traits and balance impairment, adjusting for demographic, lifestyle, and health-related factors including visual acuity. Balance impairment was defined as the inability to stand unassisted on one leg for 60 seconds.</p><p><strong>Results: </strong>During the 3-year follow-up, 2378 participants developed balance impairment. Greater retinal venular width was associated with a higher adjusted odds of incident balance impairment (odds ratio, 1.61; 95% confidence interval, 1.01-2.58). A greater retinal arteriolar area was associated with a lower adjusted odds of incident balance impairment (odds ratio, 0.82; 95% confidence interval, 0.68-0.99). Retinal arteriolar and venular tortuosity were not associated with balance (odds ratio, 0.89; 95% confidence interval, 0.74-1.07; and odds ratio, 1.20; 95% confidence interval, 0.88-1.63, respectively).</p><p><strong>Conclusions: </strong>Retinal venular widening and reduced arteriolar area are associated with developing balance impairment despite adjustment for visual acuity, cardiovascular disease, and cognition. These novel results should be confirmed and the biological mechanism clarified.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"6"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109634","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":"Cross-Sectional Profiling of Aqueous Humor VEGF-A Reflects the Tumor and Ocular Microenvironment in Retinoblastoma.","authors":"Michelle Lin, Chen-Ching Peng, Mark Reid, Elaine Huang, Nerea Goni, Kaitlyn Phung, Yilin Chen, Drishti Pandya, Brianne Brown, Bibiana J Reiser, Rachana Shah, Jesse L Berry, Liya Xu","doi":"10.1167/iovs.67.12.23","DOIUrl":"10.1167/iovs.67.12.23","url":null,"abstract":"<p><strong>Purpose: </strong>Vascular endothelial growth factor A (VEGF-A) is a key mediator of tumor angiogenesis. This cross-sectional study quantified aqueous humor (AH) VEGF-A in retinoblastoma (RB) eyes and retrospectively evaluated its association with clinical features.</p><p><strong>Methods: </strong>This study analyzed 60 AH samples: 54 from 49 RB eyes and 6 from age-matched controls with congenital cataract. From pretreatment RB eyes, six samples were collected prior to globe-salvaging treatment and five immediately after primary enucleation (PE). From post-treatment eyes, 12 samples were collected at secondary enucleation (SE), 12 during active treatment (TX), and 19 at 6 months after treatment (END). VEGF-A was measured using the Olink Proximity Extension Assay and reported as absolute concentrations (pg/mL).</p><p><strong>Results: </strong>VEGF-A concentrations (median and interquartile range [IQR]) were 259 (95% confidence interval [CI] = 140-423, IQR = 115-568) in the RB cohort, compared with 149 (95% CI = 39.8-318, IQR = 61.3-208) in cataract controls. Post-treatment levels were significantly lower than pretreatment levels (median = 182, 95% CI = 121-310, IQR = 110-423 vs. median = 1380, 95% CI = 278-18,100, IQR = 467-12,400, P < 0.001). Among treated eyes, SE samples had higher VEGF-A than END samples (median = 506, 95% CI = 120-1010, IQR = 207-926 vs. median = 129, 95% CI = 79.5-212, IQR = 79.5-212, P = 0.007).</p><p><strong>Conclusions: </strong>AH liquid biopsy was a high-yield source of VEGF-A in RB. VEGF-A concentrations were highest during primary enucleation and normalized after treatment completion. These findings support that aqueous VEGF-A reflects the intraocular microenvironment, warranting further validation to improve our understanding of its role in disease progression in RB.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"23"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181836","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":"Aspergillus Endophthalmitis: Clinical Features, Treatment Modalities, and Visual Outcomes.","authors":"Sujin Kang, Harry W Flynn, William E Smiddy, Alexander J Alfonso, Darlene Miller, Sotiria Palioura, Guillermo Amescua, Sonia H Yoo","doi":"10.1167/iovs.67.12.27","DOIUrl":"10.1167/iovs.67.12.27","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to evaluate clinical features, treatment modalities, and visual outcomes of Aspergillus endophthalmitis in a tertiary referral center.</p><p><strong>Methods: </strong>This was a retrospective consecutive case series of patients with Aspergillus endophthalmitis treated at Bascom Palmer Eye Institute from October 2014 to December 2025. Demographics, infection source, microbiologic findings, presenting features, treatments, complications, and best-corrected visual acuity (BCVA) outcomes were reviewed.</p><p><strong>Results: </strong>Fourteen eyes of 14 patients were included; median age was 62 years, and 10 patients (71%) were men. Nine eyes (64%) had exogenous disease and five (36%) had endogenous disease. Aspergillus infection was culture-proven in 12 eyes (86%) and presumed clinically in 2 (14%); identified species included A. fumigatus, A. flavus, and A. niger. Median presenting BCVA was 2.40 logMAR (approximately hand motion), and vitritis was present in all eyes. All eyes received intravitreal therapy, most commonly voriconazole (71%); systemic antifungal therapy was administered in 79%. Pars plana vitrectomy (PPV) was performed in 12 eyes (86%), including repeat PPV in 4. Median follow-up was 554 days. Final median BCVA was 2.70 logMAR (approximately light perception). Only 1 eye (7%) achieved 20/200 or better, whereas 7 eyes (50%) had final light perception or no light perception vision. Phthisis developed in three eyes (21%), and no eyes underwent evisceration or enucleation.</p><p><strong>Conclusions: </strong>Aspergillus endophthalmitis was associated with poor visual outcomes despite multimodal therapy. Exogenous and endogenous cases showed distinct clinical patterns, supporting early microbiologic diagnosis, timely antifungal therapy, and individualized surgical intervention.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"27"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181846","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":"Domestic Water Mineral Composition and Incident Glaucoma Risk: A Prospective Cohort Study From the UK Biobank.","authors":"Yukun Xiao, Weili Xie, Yiyuan Ma, Leyi Hu, Yuman Zhang, Danying Zheng, Xinyu Zhang, Hui Chen, Zhenzhen Liu, Guangming Jin","doi":"10.1167/iovs.67.12.39","DOIUrl":"https://doi.org/10.1167/iovs.67.12.39","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the association between geographically assigned domestic water mineral composition and incident glaucoma in a large prospective cohort.</p><p><strong>Methods: </strong>This study included 434,112 UK Biobank participants without glaucoma at baseline. Exposures included domestic water hardness and concentrations of calcium, magnesium, and calcium carbonate. Incident glaucoma was identified through hospital inpatient records. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustment for demographic, socioeconomic, lifestyle, and clinical covariates. Restricted cubic spline, subtype-specific, multiple imputation, proportional hazards, propensity score-matched, and biomarker analyses were conducted.</p><p><strong>Results: </strong>During a median follow-up of 14.07 years, 3125 participants developed glaucoma. For each standard deviation increase in mineral concentration, adjusted HRs were 1.10 (95% CI, 1.06-1.14) for calcium, 1.08 (95% CI, 1.05-1.12) for calcium carbonate, and 1.12 (95% CI, 1.08-1.15) for magnesium. Very hard water (>180 vs. <60 mg/L calcium carbonate, US Geological Survey classification) and hard water (≥200 vs. <200 mg/L, World Health Organization classification) were associated with higher glaucoma risk, with adjusted HRs of 1.23 (95% CI, 1.13-1.34) and 1.22 (95% CI, 1.13-1.31), respectively. Restricted cubic spline analyses showed nonlinear associations for all three mineral indicators. For calcium and calcium carbonate, HRs increased across low to intermediate concentrations and attenuated at higher concentrations. For magnesium, HRs increased gradually, mainly across low to intermediate concentrations. Estimates were consistent across sensitivity analyses.</p><p><strong>Conclusions: </strong>Geographically assigned domestic water mineral composition was associated with incident glaucoma, with distinct nonlinear patterns across mineral indicators. These observational findings require independent confirmation.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"39"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149238417","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":"A Review of PRDM13 Transcriptional Regulation in Vertebrate Retinal Development and Disease.","authors":"Emily R Nettesheim, Katherine J Wert","doi":"10.1167/iovs.67.12.33","DOIUrl":"10.1167/iovs.67.12.33","url":null,"abstract":"<p><p>The retina is a complex neuronal tissue whose development from a common retinal progenitor cell population is tightly controlled by a complex gene regulatory network driven by transcription factors. PRDM13 is a transcription factor known to play a critical role in the specification of neurons across the central nervous system, and its expression is maintained into adulthood in a limited number of neuronal types, including neurons of the dorsomedial hypothalamus and retinal amacrine cells. Dysregulation of PRDM13 has been associated with three inherited human maculopathies - North Carolina macular dystrophy (NCMD), progressive bifocal chorioretinal atrophy (PBCRA), and congenital posterior polar chorioretinal hypoplasia (CPPCRH) - indicating that PRDM13 may also play a role in development and maintenance of non-amacrine retinal cell types. Herein, we review the known roles of PRDM13 across the developing central nervous system to provide a comprehensive understanding of PRDM13's general and tissue-specific functions, as well as how PRDM13 dysregulation may lead to improper macular development and disease. Future studies into PRDM13 and its downstream regulatory network will be important to provide critical insights into the regulation of cell fate decisions in the developing retina.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"33"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193830","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":"Effect of Prematurity on Foveal Development During Infancy: Increased Foveal Inner and Outer Retina Layer Thicknesses in Extremely Premature Infants.","authors":"Xiao Yi Zhou, Gui-Shuang Ying, Vincent Tai, Shwetha Mangalesh, Cynthia A Toth, Xi Chen","doi":"10.1167/iovs.67.12.4","DOIUrl":"10.1167/iovs.67.12.4","url":null,"abstract":"<p><strong>Purpose: </strong>Foveation and inner retinal displacement are arrested in extremely premature infants through term equivalent age. We hypothesize that the effect of prematurity continues to impact the developing fovea in later stages of foveal development, well after term equivalent age.</p><p><strong>Methods: </strong>Infants enrolled in the STudy of Eye imaging in Preterm infantS (BabySTEPS1; NCT02887157) were imaged at four and nine months' corrected age. For infants with gradable imaging, foveal and parafoveal inner (IRL) and outer (ORL) retinal layer thicknesses were measured, with parafoveal/foveal thickness (P/F) ratios calculated. Univariate and multivariate regression analyses were performed to determine associations of birth and perinatal factors with foveation, and the effect of gestational age (GA) and history of macular edema on foveal thickness measurements.</p><p><strong>Results: </strong>In multivariate analysis of 99 eyes (56 infants) at four months and 70 eyes (44 infants, 34 infants overlapped with the four-months group) at nine months' corrected age, decreased P/F ratio was associated with lower GA (per week decrease) (four months: β (SE) = -0.109 (0.010, P < 0.0001; nine months: β (SE) = -0.063(0.011), P = 0.0005). Lower GA was associated with thicker foveal IRL (four months: β (SE) = 5.91 (0.76) µm, P < 0.0001; nine months: β (SE) = 3.95 (0.99) µm, P = 0.004) and ORL (four months: β (SE) = 4.86 (1.10) µm, P = 0.003; nine months: β (SE) = 4.46 (1.13) µm, P = 0.002). History of macular edema was associated with higher P/F ratios and thicker foveal ORL but not foveal IRL.</p><p><strong>Conclusions: </strong>Development of both inner and outer retina is altered in prematurity, and manifests from the time of preterm birth through infancy. During the first year of life, the most premature infants had shallower foveal pits and thicker IRL and ORL. Infants with a history of macular edema had thicker ORL.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"4"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13648560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149109641","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 Transcriptomic Profiling Reveals DECTIN-1-Mediated Immune Responses in Acanthamoeba Keratitis.","authors":"Jinding Pang, Zhenyu Wei, Yuheng Zhang, Yuan Wei, Qingquan Shi, Qiankun Chen, Zijun Zhang, Sitong Shen, Bo Peng, Ahyan Ilman Qudsi, Sizhe Ji Wu, Qingfeng Liang","doi":"10.1167/iovs.67.12.25","DOIUrl":"10.1167/iovs.67.12.25","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to investigate the dynamic immune response and the role of DECTIN-1 in Acanthamoeba keratitis (AK).</p><p><strong>Methods: </strong>The AK mouse model was established, and corneal tissue samples were collected at 1, 3, and 7 days post-infection (dpi). Transcriptomic profiling was performed to analyze differentially expressed genes and enriched Gene Ontology terms. Immune cell infiltration was estimated using ImmuCellAI-mouse. The expression of DECTIN-1 and associated signaling molecules was validated using quantitative PCR, immunostaining, and Western blotting. In vitro experiments were conducted to assess DECTIN-1 expression in human corneal epithelial cells (HCECs).</p><p><strong>Results: </strong>AK progression was characterized by dynamic changes, with peak inflammatory responses at 3 dpi. Immune infiltration analysis revealed early innate immune activation followed by adaptive immune involvement at later stages. Temporal transcriptome analysis identified DECTIN-1 as a significantly upregulated gene throughout disease progression. Activation of the DECTIN-1/SYK/NF-κB signaling pathway was associated with increased expression of pro-inflammatory cytokines. In vitro experiments confirmed that Acanthamoeba directly induced DECTIN-1 expression in HCECs.</p><p><strong>Conclusions: </strong>DECTIN-1 was dynamically upregulated during AK and may play a potential role in mediating innate immune responses and shaping immune cell dynamics. These findings provided new insights into AK pathogenesis and indicated DECTIN-1 as a potential therapeutic target.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"25"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181263","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":"Individual-Eye Pharmacokinetics of Intravitreal Ranibizumab: Linking Ocular Geometry to Drug Retention Using MRI and Modeling.","authors":"Patricia Lamirande, Eamonn A Gaffney, Michael Gertz, Basil Künnecke, Thomas Bielser, Andreas Bruns, Jessica R Crawshaw, Uwe Wessels, Antonella Rampazzo, Philip K Maini, Antonello Caruso","doi":"10.1167/iovs.67.12.31","DOIUrl":"10.1167/iovs.67.12.31","url":null,"abstract":"<p><strong>Purpose: </strong>The purpose of this study was to quantify the influence of ocular geometry on intravitreal (IVT) ranibizumab pharmacokinetics (PKs) in rabbits by integrating magnetic resonance imaging (MRI)-derived geometries, diffusion-based modeling, and PK measurements.</p><p><strong>Methods: </strong>MRI was performed to obtain detailed ocular geometries in 39 New Zealand White (NZW) rabbits. Ranibizumab PKs were assessed in the same animals by serial aqueous humour (AH) sampling following single or three 0.5 mg doses. Individual eye parameters were estimated using profile likelihood analysis. A mean first passage time model was developed to predict ocular half-life as a function of eye size and injection location. Simplified ocular models parameterized by axial length (AL) were constructed to assess whether reduced anatomic representations capture population-level trends.</p><p><strong>Results: </strong>MRI-derived vitreous geometries enabled quantification of inter-eye anatomic variability. The study cohort of adult rabbits exhibited a limited range of AL and vitreous volume compared to human variability. Modeling predicted increased ocular half-life with eye size, a trend reproduced by simplified AL-based models. Experimentally estimated half-lives ranged between 2.8 and 4.9 days and showed weak correlation to AL and vitreous volume. The population mean half-life was 3.67 days, consistent with previous results.</p><p><strong>Conclusions: </strong>This study provides a quantitative framework for analyzing IVT PKs at the level of individual eyes. Modeling predicts that ocular geometry influences drug elimination, and this relationship was also detected experimentally in rabbits, albeit over a limited anatomic range. Greater variability in human eye size may therefore contribute to interindividual PK differences and warrants further investigation, as it may inform personalized dosing strategies.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"31"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193824","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-Cell Sequencing Reveals Androgen Deficiency Arrests Meibocyte Differentiation and Impairs EMC-Mediated Lipid Metabolism.","authors":"Shenchuan Qian, Zihao Liu, Mike Pan, Meiling Zhu, Juan Li, Yuyang Fu, Qian Li, Zhiwei Zha, Ying Feng, Wei Chen","doi":"10.1167/iovs.67.12.46","DOIUrl":"https://doi.org/10.1167/iovs.67.12.46","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the cellular dynamics of androgen-deficient meibomian gland dysfunction (MGD) and to elucidate the molecular mechanisms limiting the structural regenerative efficacy of topical dihydrotestosterone (DHT) treatment.</p><p><strong>Methods: </strong>Single-cell RNA sequencing (scRNA-seq) was performed on meibomian glands from sham-operated controls, castrated mice, and castrated mice receiving topical 0.08% DHT. We performed comparative analyses to quantify changes in cell composition, reconstruct differentiation trajectories, and systematically profile alterations in metabolic pathways and organelle homeostasis networks.</p><p><strong>Results: </strong>Castration arrested meibocyte differentiation and redirected cell fate commitment. Pseudotime trajectory analysis revealed a pronounced shift from the meibocyte lineage toward ductal and progenitor fates, accompanied by comprehensive downregulation of lipogenic genes (e.g., Fasn, Awat2). This fate reprogramming was coupled with disrupted endoplasmic reticulum (ER) homeostasis, including suppression of the ER membrane protein complex (EMC) and impaired lipid assembly machinery. Topical DHT treatment partially restored meibocyte differentiation but failed to fully recover gland morphology. Furthermore, rapid metabolic reactivation following DHT treatment outpaced ER capacity recovery, inducing proteostatic stress.</p><p><strong>Conclusions: </strong>Androgen deficiency drives MGD through dual mechanisms: reprogramming of meibocyte cell fate toward non-lipogenic lineages and suppression of EMC-mediated stabilization of ER-resident lipogenic enzymes. The resulting temporal mismatch between lipogenic reactivation and ER capacity recovery upon DHT treatment induces proteostatic stress, limiting the efficacy of androgen monotherapy and identifying the EMC-ER axis as a candidate therapeutic target for combinatorial intervention.</p>","PeriodicalId":14620,"journal":{"name":"Investigative ophthalmology & visual science","volume":"67 12","pages":"46"},"PeriodicalIF":5.5,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149244732","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}