Chronological age incompletely captures heterogeneity in biological aging. In this prospective study of 45,819 UK Biobank participants, we developed a multimodal ocular aging index (MOAI) by integrating ophthalmic phenotypes with plasma proteomic and metabolomic profiles using machine learning. The MOAI quantifies divergence between ocular biological and chronological age. Over 13.80 years of follow-up, accelerated ocular aging was significantly associated with higher risks of incident age-related macular degeneration and cataract, even after adjustment for chronological age and established risk factors. Incorporation of the MOAI significantly improved risk reclassification beyond traditional predictors. Explainable modeling and pathway enrichment analyses identified inflammation-related proteins and pathways, including cytokine-cytokine receptor interactions and PI3K-Akt signaling, as key drivers of accelerated ocular aging. These findings establish a multimodal framework for quantifying organ-specific biological aging, link ocular aging to systemic inflammatory processes, and highlight the eye as a sensitive readout of aging biology with implications for healthspan.

Given the genetic predisposition to myopia, polygenic risk scores (PRS) have been proposed as a tool for early risk identification. This study assessed the discriminatory ability of PRS in myopia prediction systematically and compared the performance of different PRS models. This systematic review followed PRISMA guidelines and was preregistered in PROSPERO (CRD420251180577). Five databases (PubMed, Web of Science, Cochrane Library, EMBASE and Scopus) were searched from inception to October 11, 2025. Eligible studies were required to develop or validate myopia prediction models that incorporated PRS and to report at least one discrimination metric. The methodological quality and risk of bias were assessed independently using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Ten studies met the inclusion criteria. The discriminatory performance of PRS-only models ranged from an area under the receiver operating characteristic curve (AUC) of 0.51–0.80, whereas combined models integrating PRS with clinical or other factors demonstrated a higher performance range (AUC 0.57–0.99). Predictive performance varied according to myopia phenotype, ancestry, and PRS construction strategy. Models tended to achieve stronger discrimination for high or moderate myopia compared with low myopia, and performed better in European populations than in other ancestry groups. Increasing the number of single-nucleotide polymorphisms included in the PRS yielded only modest incremental improvements in predictive accuracy. Across all comparisons, combined models consistently outperformed PRS-only models. PRS contributes to myopia risk prediction, particularly when integrated with clinical or other risk factors, and its predictive performance varies across myopia phenotype, ethnicity, age and the number of single-nucleotide polymorphisms. Further large-scale, multi-ancestry validation and evaluation of implementation feasibility are needed before PRS can be incorporated effectively into routine myopia prevention and risk stratification strategies.

BACKGROUND:Age-related cataract (ARC) is a leading cause of visual impairment and blindness among older adults, yet effective pharmacological options remain limited. This study aimed to identify candidate circulating metabolic biomarkers and pathways associated with ARC risk. METHODS:Genetic data for blood metabolites and ARC were derived from three metabolite genome-wide association studies (GWASs) and FinnGen. Mendelian randomization (MR) analyses assessed associations between 121 metabolites and ARC. UK Biobank cohort analyses evaluated whether MR-identified associations were observed in longitudinal real-world data. Bioinformatics and molecular docking analyses were used to explore potential mechanistic pathways and applicability. RESULTS:MR analyses identified protective associations of 1,5-anhydroglucitol (odds ratio (OR) = 0.60, 95% confidence interval (CI), 0.43-0.82), triglycerides in low-density lipoprotein (LDL) (OR = 0.95, 95% CI, 0.92-0.98), linoleic acid (OR = 0.92, 95% CI 0.88-0.97), and polyunsaturated fatty acids (PUFAs) (OR = 0.93, 95% CI, 0.89-0.97) with ARC. In cohort analysis, linoleic acid (hazard ratio (HR) = 0.96, 95% CI, 0.94-0.98) and PUFAs (HR = 0.96, 95% CI, 0.94-0.98) were associated with a lower incident ARC risk, whereas triglycerides in LDL was not significant overall, although an inverse association was observed in participants aged ≥ 60 years (HR = 0.97, 95% CI, 0.95-0.99). Bioinformatics analyses identified candidate genes and pathways, and docking suggested potential interactions between linoleic acid and candidate proteins. CONCLUSIONS:Linoleic acid and PUFAs showed consistent inverse associations with ARC. Further experimental studies are needed to validate their biological relevance and clinical utility.

Aims to outline the application of neuroeconomics in paediatric myopia prevention, offering a framework for designing public health interventions that target decision-making mechanisms such as intertemporal choice, social preferences and neurohormonal regulation. We synthesized theories and empirical evidence from neuroeconomics, psychology and neuroscience. Multimodal approaches-including behavioural tasks (e.g. delay discounting, Ultimatum Game), functional near-infrared spectroscopy (fNIRS), pupillometry and salivary assays-were used to evaluate how interventions influence neurocognitive processes. Neuroeconomic research reveals that myopia-related behaviours involve neural competition between impulsive and regulatory systems, temporal discounting of future rewards and modulation by social norms and neurohormones (e.g. dopamine, oxytocin). Intervention strategies incorporating immediate incentives, social normative feedback, environmental nudges and reduced cognitive effort show potential in promoting outdoor time and behaviour change. Neuroeconomics provides a novel framework for myopia prevention by targeting neural computation mechanisms. Future research should focus on cross-cultural and developmental validation while addressing ethical and implementation challenges to advance precise and equitable public health strategies.

BACKGROUND:High myopia increases the risk of pathological ocular changes that may lead to irreversible vision loss. Therefore, the identification of potential biomarkers and therapeutic targets for high myopia is essential for early intervention and prevention. METHODS:Summary statistics for 122 blood metabolites were obtained from three genome-wide association studies (GWASs), whereas data on high myopia were derived from a large GWAS conducted with 50,372 participants from the UK Biobank. Mendelian randomisation (MR) analyses were conducted to assess the causal relationships between blood metabolites and high myopia. A real-world case-control study was conducted to validate the causal associations identified in the MR analyses. RESULTS:The systematic MR analysis identified 5 blood metabolites as both biomarkers and potential drug targets for high myopia, including glutamine (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.97-1.00), tyrosine (OR: 0.98; 95% CI: 0.97-0.99), degree of unsaturation (OR: 0.98, 95% CI: 0.98-0.99), docosahexaenoic acid (DHA) (OR: 0.99; 95% CI: 0.98-1.00) and isobutyrylcarnitine (OR: 1.09, 95% CI: 1.05-1.13). The case-control study indicated that the levels of glutamine (OR = 0.76, 95% CI: 0.58-0.98) and tyrosine (OR = 0.72, 95% CI: 0.55-0.94) were significantly associated with a decreased risk of high myopia. CONCLUSIONS:Systematic MR analysis suggested that glutamine, tyrosine, the degree of unsaturation, DHA, and isobutyrylcarnitine may represent promising drug targets for high myopia prevention. Further investigations are needed to validate the therapeutic efficacy and elucidate the underlying mechanisms involved.

This study aims to forecast future trends and quantify the contributions of key determinants, extending current evidence for tailored interventions The study used data from the Global Burden of Disease Study 2021 for children, adolescents and young adults aged 0–24 years. Temporal trends were analysed with joinpoint regression, while health inequalities were assessed using the slope index of inequality (SII) and concentration index (CIx). Bayesian age-period-cohort (BAPC) modelling and XGBoost were employed to project prevalence and years lived with disability (YLDs) and SHAP values were used to quantify the contributions of key predictors. A slight but significant global decrease was observed in both prevalence (average annual percent change, AAPC: –0.05

TOPIC:To determine whether the transparency of conflicts of interest (COI) declarations is associated with study outcomes and methodological quality in randomized controlled trials (RCTs) of myopia controlled interventions. CLINICAL RELEVANCE:Myopia control practice is guided largely by RCT evidence, much of which involves industry participation. Variability in the transparency of COI disclosures may influence how such evidence is interpreted for clinical decision-making. METHODS:PubMed, Embase, Cochrane Library, and Web of Science were systematically searched from inception to October 6, 2025. Eligible studies were RCTs of myopia controlled interventions in children or adolescents with at least 6 months of follow-up and reporting cycloplegic spherical equivalent and/or axial length outcomes. COI declaration transparency was categorized a priori into predefined levels. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Associations between COI transparency and study conclusions, statistical significance, and effect sizes were evaluated using cross-sectional, multiple meta-regression models. The protocol was registered in PROSPERO (CRD420261291949). RESULTS:A total of 134 RCTs were included. Sixteen trials (11.9%) did not report a COI statement, 85 (63.4%) provided simple declarations of no conflicts, 14 (10.4%) reported intermediate disclosures, and 19 (14.2%) provided detailed COI statements. Distributions of overall risk of bias and the domain of selective outcome reporting differed significantly across COI transparency categories, with a higher proportion of low-risk judgments observed in trials with more detailed COI disclosures (both P < .01). Overall, COI transparency was not significantly associated with study outcomes. However, in stratified analyses, greater COI transparency was significantly associated with more favorable study conclusions among trials evaluating optical interventions, even after adjustment for industry funding and other covariates (odds ratio = 2.66, 95% confidence interval: 1.19-5.92, P = .02). Similar patterns were observed in trials with larger sample sizes and those published in higher-impact factor journals, although these associations were attenuated after accounting for industry funding. CONCLUSION:Transparency in COI declarations demonstrates context-specific relationships with study conclusions and reporting quality in myopia controlled trials. While transparent disclosure is essential for research integrity, its interpretation should be integrated with funding context when evaluating evidence to inform clinical practice.

Purpose: The purpose of this study was to investigate the prospective association between intrinsic capacity (IC) and the risk of incident glaucoma. Methods: We performed prospective cohort analyses among 397,881 UK Biobank participants. An IC deficit composite score was constructed based on six IC components. Cox proportional hazards models were utilized to estimate the associations of IC deficit scores and individual IC components with the risk of glaucoma. We tested gene-IC interactions using polygenic risk score (PRS) data for glaucoma. Results: During a median follow-up time of 13.8 years, 6264 glaucoma cases were identified, encompassing 1661 cases of primary open-angle glaucoma (POAG). After adjustments for glaucoma PRS and conventional risk factors, each 1-point increase in IC score was associated with a 12% higher glaucoma risk (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.09-1.14). Participants with no less than 4 IC deficits had a 65% increased risk compared with those with no deficits (HR = 1.65, 95% CI = 1.43-1.90). Evidence of interaction between IC and glaucoma PRS was observed on the multiplicative scale, whereas no significant interaction was found on the additive scale. Population attributable fraction (PAF) analysis suggested that 12.0% of glaucoma cases could be prevented if all individuals maintained optimal IC. Conclusions: Impaired IC is significantly associated with an elevated risk of developing glaucoma, highlighting the value of nurturing and maintaining IC in preventing glaucoma. Translational Relevance: Our findings suggest that assessing and maintaining IC may serve as a practical strategy for early identification and prevention of glaucoma in clinical and population health settings.

Per- and polyfluoroalkyl substances (PFAS) have raised increasing concerns due to their potential neurotoxicity; however, their effects on retina, a highly specialized neural tissue, remain unclear. This study aimed to investigate the retinal toxicity of PFAS in adolescents and to elucidate underlying molecular mechanisms and therapeutic targets. A cross-sectional study involving 1686 Chinese adolescents was conducted to evaluate associations between serum PFAS concentrations and retinal structural characteristics. In parallel, toxicogenomic analyses were performed to identify key genes associated with PFAS exposure and retinal diseases. Correspondingly, in vitro experiments were conducted to reveal the potential molecular mechanisms underlying the cytotoxic effects of PFAS on retinal ganglion cells (RGCs). Higher serum levels of PFOA (β = -0.05, P = 0.01), PFOS (β = -0.06, P = 0.04) and PFHxS (β = -0.11, P = 0.03), were negatively associated with global retinal nerve fiber layer (RNFL) thickness. Applying toxicogenomic screening, nine hub genes related to PFAS (e.g., CCL2, TNF-α, and TLR4) were identified to be enriched in inflammatory pathways. Mechanistically, apoptotic cell death in R28 and RGCs were promoted by PFAS exposure, characterized by elevated cleaved PARP and cleaved Caspase-3. This study provides evidence that PFAS exposures are correlated with retinal neurotoxicity in adolescents through inflammatory activation and apoptosis. The identified gene signatures highlight potential targets for prevention and therapeutic intervention.

Purpose: Household air pollution (HAP) is a major environmental risk factor affecting nearly 3 billion people worldwide, and is strongly associated with cataract formation. However, the temporal dynamic and future trends of the global cataract burden attributable specific to HAP remain insufficiently understood. Unlike previous studies focusing on the overall cataract burden, this study quantifies the independent contribution of HAP as an intervenable environmental risk factor. Methods: Using data from the Global Burden of Disease database, we assessed global, regional, and national cataract burden attributable to HAP from 1990 to 2021. Joinpoint regression evaluated temporal trends, Age-Period-Cohort modeling elucidated drivers of burden changes, and health inequality was examined. Future burden was projected using ARIMA and ARIMA-LSTM hybrid models. Results: In 2021, global HAP-attributable cataract burden reached 1956.32 thousand years lived with disability (YLDs), with age-standardized YLDs rate (ASYR) of 22.84 per 100,000. From 1990 to 2021, global YLDs increased steadily, with females consistently exhibiting higher burden than males, while ASYR declined. South Asia and East Asia bore the highest burden, with low socio-demographic index (SDI) regions most affected. Forecasts indicate global YLDs will rise to 1987.94 thousand by 2035, although ASYR will continue declining. Conclusion: HAP is strongly associated with cataracts globally. Females and people living in low-SDI regions are disproportionately affected. There is an urgent need to strengthen clean energy promotion, public health education, and targeted prevention programs in high-burden settings to reduce the cataract burden attributed to HAP.

AIMS:The impact of genetic variants on high myopia (HM) remains unclear. This study aims to systematically evaluate the relationship between genetic polymorphisms and HM. METHODS:Eligible studies were retrieved from five databases (PubMed, Web of Science, Cochrane, Embase and Scopus) up to 18 January 2025. We included all case-control studies that examined the association of single nucleotide polymorphisms (SNPs) with HM susceptibility. Fixed or random effects models were used to evaluate pooled ORs and CIs for each SNP in HM. Sensitivity analyses were conducted to assess the reliability and stability of the results. RESULTS:Seventy-six studies (89 separate cohorts) were eligible for the meta-analysis of HM, involving 77 SNPs in 34 genes. Twenty-two SNPs in 13 genes (rs1516794 in ACAN gene; rs2269336 in COL1A1 gene; rs2071861 and rs2009066 in CRYBA4 gene; rs339501 in FGF10 gene; rs698047 in HIVEP3 gene; rs3741834, rs2300588, rs3759223 and rs7135740 in LUM gene; rs9318086 in MIPEP gene; rs243845 and rs1861320 in MMP2 gene; rs662702 and rs644242 in PAX6 gene; rs8027411 and rs17175798 in RASGRF1 gene; rs7839488, rs4395927 and rs6469937 in SNTB1 gene; rs1800470 in TGFβ1 gene; and rs7829127 in ZMAT4 gene) showed significant associations with HM. CONCLUSION:This study identified 22 SNPs in 13 genes (ACAN, COL1A1, CRYBA4, FGF10, HIVEP3, LUM, MIPEP, MMP2, PAX6, RASGRF1, SNTB1, TGFβ1 and ZMAT4) as potential genetic biomarkers for HM. Future research should conduct large-scale genome-wide association studies across diverse populations to yield more robust evidence.

Studies show that exposure to air pollutants is linked to eye diseases, but they don't specify the impact on different eye structures. This study aims to analyse the risk of ocular surface, anterior and middle segment and fundus eye diseases among individuals exposed to common and specific air pollutants. Seven databases were searched for relevant studies published between January 2000 and August 2024. Inclusion criteria encompassed individuals of all ages, with studies providing associations between common air pollutants (carbon monoxide [CO], nitrous oxide [NO], nitrogen dioxide [NO2], sulphur dioxide [SO2], ozone [O3], black carbon, particulate matter [PM], environmental tobacco smoke [ETS]), specific air pollutants (volatile organic compounds [VOCs] in cosmetics, smoke from indoor solid fuel cookers, biomass fuel use and road dust). Pooled odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated. A total of 55 studies were included. Consistent evidence of associations was found between air pollutant exposure and eye diseases, with 51 studies reporting positive associations. The combined overall result was OR = 1.26 (95% CI, 1.20-1.32). Additionally, evidence of associations was observed for ocular surface diseases (OR = 1.29, 95% CI, 1.20-1.39), anterior and middle segment diseases (OR = 1.22, 95% CI, 1.14-1.31) and fundus oculi diseases (OR = 1.35, 95% CI, 1.17-1.57). In conclusion, the meta-analysis suggests air pollutant exposure is associated with ocular diseases, with the highest pooled risk for fundus diseases, though direct comparisons are limited by study heterogeneity.

Background: Although previous studies indicate that perceived social support might be associated with adolescent psychological problems, the specific mechanism has not been thoroughly discussed. Based on theoretical and empirical research on problematic Internet use (PIU) and sleep quality, this study explored whether they play a mediating role between perceived social support and symptoms of depression and anxiety among adolescents. Furthermore, we investigated whether these relationships varied by place of residence. Methods: A sample of 2115 Chinese adolescents was included, and analyzed data related to perceived social support, PIU, sleep quality, symptoms of depression and anxiety, and sociodemographic variables. Correlation analysis, mediation, and moderation analysis were mainly used. Results: Perceived social support was negatively correlated with depressive symptoms (r = -0.22, p < 0.001) and anxiety symptoms (r = -0.20, p < 0.001) among adolescents. PIU and sleep quality played a chain mediating role in the relationship between perceived social support and symptoms of depression and anxiety in adolescents. Additionally, the place of residence moderated the relationships between perceived social support and PIU and symptoms of depression and anxiety. Perceived social support was a significant negative predictor of PIU and symptoms of depression and anxiety among adolescents in urban areas but not in rural areas. Conclusion: The findings suggest that low levels of perceived social support may lead to more PIU and poorer sleep quality, which may further increase the risk of symptoms of depression and anxiety in adolescents, especially in urban areas.

Abstract： Background: While multimorbidity patterns in Western populations are well-documented, their characterization and impact on Health-related Quality of Life (HRQoL) in China\'s aging population remain underexplored. This study aimed to identify multimorbidity patterns and their associations with HRQoL in China. Methods: A survey was conducted in 148 cities across China between June 20 and August 31, 2022, using quota sampling. A total of 8,725 participants aged over 45 years were included in the current study. Latent class analysis (LCA) was performed to identify distinct multimorbidity classes based on 14 self-reported chronic conditions. Model selection was based on appropriate BIC, entropy, and probability distributions. Tobit regression models, accounting for the ceiling effects of the EQ-5D index, were used to analyze the relationship between multimorbidity patterns and HRQoL. Results: Four distinct multimorbidity patterns were identified by LCA: relatively healthy class (74.3%), cardio-metabolic class (13.2%), musculoskeletal class (11.4%), and multidisease class (1.1%). Compared to the relatively healthy group, the multidisease class had the largest reduction in EQ-5D index (?0.141, 95% CI: ?0.173, ?0.109), followed by cardio-metabolic and musculoskeletal classes. Pain/discomfort was the most affected HRQoL domain across all multimorbidity patterns, with the strongest association observed in the multidisease class (OR = 5.98, 95% CI: 3.40, 11.07). Conclusion: Distinct multimorbidity patterns were significantly associated with lower HRQoL, particularly in dimensions of pain and anxiety. Targeted interventions for multimorbidity patterns may optimize resource allocation in China\'s primary care system. Further studies should be carried out to investigate effective measures to improve HRQoL of the elderly with multimorbidity.

Myopia is highly prevalent among children and adolescents and results from abnormal refractive development. Less outdoor time as well as more near work have been recognised as major risk factors for myopia. This study analysed the major environmental factors related to myopia, such as outdoor activities and near work, and reviewed the potential mechanisms of myopia development. A systematic search was conducted across PubMed, Web of Science, Cochrane Library and Ovid databases within the last two decades up to November 2024. This review followed the recommendations of the PRISMA Statement and only full-text review articles in English were included. Summarising the findings from 13 review articles, the environmental risk factors for myopia included lighting features such as low illumination and monochromatic light as well as aspects of the visual scene, for example, the presence of low spatial frequencies and hyperopic defocus. These particular visual stimuli may contribute to the onset and progression of myopia and increase the risk of retinal disorders by reducing choroidal blood flow, leading to scleral hypoxia and remodelling. When analysing environmental risk factors, it is challenging to isolate the individual contributions of outdoor time and near work. Furthermore, previous studies used different definitions of environmental exposures. Future research needs quantitative, objective and standardised measures to improve the comparability and consistency between studies. In addition, work should focus on different ethnic populations and gene–environment studies, so as to determine the influence of environmental risk factors on myopia.

PURPOSE:To elucidate the association of visual impairment (VI) on both all-cause and cause-specific mortality. DESIGN:Population based cohort study. METHODS:A total of 12,510 US adults aged 40 years or older from the US National Health and Nutrition Examination Survey (1999-2008) and 95,477 UK adults aged 40 years or older from the UK Biobank (2006-2010). Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% CIs. Competing risk models were used to investigate the influence of VI on cause-specific mortality. RESULTS:After adjusting for socio-demographic information, lifestyle factors, and health status, the HR for all-cause mortality was significantly elevated among individuals with VI (US NHANES: HR = 1.63, 95% CI: 1.39-1.91; UK Biobank: HR = 1.25, 95% CI: 1.08-1.44). A significant association between VI and heart disease-specific mortality was observed in the US NHANES (HR = 1.76, 95% CI: 1.33-2.32), which was confirmed in the competing risk analysis (HR = 1.34, 95% CI: 1.12-1.61). CONCLUSIONS:VI is associated with elevated hazards of all-cause and heart disease-specific mortality. Early detection and management of VI, integrated with comprehensive cardiovascular risk prevention, may have significant public health implications.

Problematic Internet use (PIU) has been shown to be associated with multiple adverse outcomes, and its prevalence has increased significantly in recent years. The influence of personality and family factors on PIU has been studied separately, but the combined effect has not been well explored. This study aimed to examine the associations of personality traits and family health with different dimensions of PIU through network analysis. A total of 21,916 individuals from the psychology and behavior investigation of Chinese residents were included in the current study. A regularized partial correlation network consisting of different dimensions of family health, personality and PIU was constructed. Network Comparison Tests were applied to investigate the differences between men and women within the network. "Family social/emotional health processes" had the highest expected influence centrality, followed by "Family healthy lifestyle" and "Control disorder". "Family external social supports", "Family social/emotional health processes" and "Family healthy lifestyle" were identified as bridge symptoms. Family health play an important role in the combined network, but some personality traits may have a strong deactivate impact on this association. Special attention to family health may be critical to preventing PIU and its related adverse outcomes in the general population.

Purpose:This investigation aimed to elucidate the causal role of inflammatory cytokines in the risk of developing refractive errors. Methods:Genetic variants previously associated with inflammatory cytokines served as instrumental variables in genome-wide association studies (GWASs) of European ancestry. Bidirectional two-sample Mendelian randomization (MR) analyses were conducted using summary data from GWAS meta-analyses. Rigorous sensitivity analyses were performed to validate the reliability of the MR results. Results:We found that, for every unit increase in interleukin 1 receptor antagonist (IL1RA) and interleukin 2 (IL2), there was a corresponding decrease in the prevalence of myopic refractive errors by 0.235 (95% confidence interval [CI], 0.050-0.419 for fixed effects; 95% CI, 0.125-0.345 for random effects) and 0.132 (95% CI, 0.032-0.231 for fixed effects; 95% CI, 0.044-0.220 for random effects), respectively. No substantial causal associations were observed for IL1α, IL1β, IL12p70, or monocyte chemoattractant protein 1 (MCP1) with refractive errors. Conversely, reverse MR analyses failed to indicate a causal influence of refractive errors on IL1RA and IL2. Conclusions:The present study offers evidence for a causal link between inflammatory cytokines and refractive errors, which could have significant implications for the early detection, surveillance, and management of refractive errors. Translational Relevance:Our study underscores the importance of IL1RA and IL2 in the prevention and management of refractive errors, suggesting the feasibility of strategies for early identification, continuous surveillance, and the deployment of focused therapeutic approaches.

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are emerging contaminants widely found in drinking water and food, potentially entering the human body through these sources. To investigate these effects, we simulated PFAS exposure doses in animal models, ranging from general population to occupational levels, and analyzed blood and spleen samples. Epidemiological studies linked PFAS exposure to immunosuppression and hematotoxicity, while toxicogenomic analyses validated the underlying biological mechanisms. PFAS exposure caused immunotoxic effects, including altered blood parameters and lymphocyte edema. Cellular abnormalities such as decreased cytoplasmic density, incomplete rough endoplasmic reticulum, chromatin condensation, lymphocyte nuclear shrinkage, and reduced mitochondrial cristae were observed. Epidemiological evidence revealed a dose-response relationship between mixed PFAS exposure and hematologic indices such as hematocrit (HCT), hemoglobin (HGB), platelet count (PLT), platelet-to-lymphocyte ratio (PLR), white blood cell count (WBC), monocyte percentage, and platelet large cell ratio (PLCR), with perfluorooctanoic acid (PFOA) playing a dominant role. Toxicogenomic analysis identified genes associated with platelets, anemia, and leukocyte function, linked to inflammation, Th17 cell differentiation, apoptosis, lipid metabolism, atherosclerosis, and JAK-STAT signaling. This study provides novel insights into the hematotoxicity and immunosuppressive effects of mixed PFAS exposure, emphasizing the need for PFAS substitution, removal, and policies addressing mixed exposures to protect public health.

BackgroundPlatelet parameters have been linked with glaucomatous optic neuropathy but whether they were associated with retinal nerve fiber layer (RNFL) thickness among healthy individuals remains unclear. We aim to determine the relationship between different platelet parameters and RNFL thickness in healthy university students.MethodsThe Dali University Students Eye Health Study is a university-based, cross-sectional study in southwestern China in 2021. RNFL thickness was measured automatically using an optical coherence tomography scanner. An automated hematology analyzer was used to analyze the platelet parameters including platelet (PLT) count, platelet distribution width (PDW), mean platelet volume (MPV) and plateletcrit (PCT). Linear regression models and generalized additive models were established to examine the associations of platelet parameters with RNFL thickness.ResultsA total of 1905 participants with valid RNFL thickness and platelet parameters data were included in the current analysis. Per unit increase in the levels of MPV and PDW was associated with a decrease of 0.74 μm (P = 0.04) and 0.35 μm (P = 0.04) in RNFL thickness in multivariable-adjusted model. Subgroup analyses indicated that the association between MPV and RNFL thickness was present in male students. A non-linear trend in the association of MPV with RNFL thickness were observed (P = 0.04).ConclusionIncreased levels of MPV and PDW were associated with thinner RNFLs among university students, suggesting that the platelet parameters, a simple, global, and economical markers, have the potentials to be an additional valuable biomarker for predicting the change of RNFL thickness and onset of RNFL-related nerve diseases in late adulthood.