Role of N6-methyladenosine-related lncRnas in pseudoexfoliation glaucoma.

To explore the role of lncRNA m6A methylation modification in aqueous humour (AH) of patients with pseudoexfoliation glaucoma (PXG). Patients with open-angle PXG under surgery from June 2021 to December 2021 were selected. Age- and gender-matched patients with age-related cataract (ARC) were chosen as control. Patients underwent detailed ophthalmic examinations. 0.05-0.1 ml AH were extracted during surgery for MeRIP-Seq and RNA-Seq. Joint analysis was used to screen lncRNAs with differential m6A methylation modification and expression. Online software tools were used to draw lncRNA-miRNA-mRNA network (ceRNA). Expression of lncRNAs and mRNAs was confirmed using quantitative real-time PCR. A total of 4151 lncRNAs and 4386 associated m6A methylation modified peaks were identified in the PXG group. Similarly, 2490 lncRNAs and 2595 associated m6A methylation modified peaks were detected in the control. Compared to the ARC group, the PXG group had 234 hypermethylated and 402 hypomethylated m6A peaks, with statistically significant differences (| Fold Change (FC) |≥2, p < 0.05). Bioinformatic analysis revealed that these differentially methylated lncRNA enriched in extracellular matrix formation, tight adhesion, TGF- ß signalling pathway, AMPK signalling pathway, and MAPK signalling pathway. Joint analysis identified 10 lncRNAs with differential m6A methylation and expression simultaneously. Among them, the expression of ENST000000485383 and ROCK1 were confirmed downregulated in the PXG group by RT-qPCR. m6A methylation modification may affect the expression of lncRNA and participate in the pathogenesis of PXG through the ceRNA network. ENST000000485383-hsa miR592-ROCK1 May be a potential target pathway for further investigation in PXG m6A methylation.

Fundus Tessellation and Parapapillary Atrophy, as Ocular Characteristics of Spontaneously High Myopia in Macaques: The Non-Human Primates Eye Study.

Purpose: This study aimed to evaluate the ocular characteristics associated with spontaneously high myopia in adult nonhuman primates (NHPs). Methods: A total of 537 eyes of 277 macaques with an average age of 18.53 ± 3.01 years (range = 5-26 years), raised in a controlled environment, were included. We measured ocular parameters, including spherical equivalent (SE), axial length (AXL), and intraocular pressure. The 45-degree fundus images centered on the macula and the disc assessed the fundus tessellation and parapapillary atrophy (PPA). Additionally, optical coherence tomography (OCT) was used to measure the thickness of the retinal nerve fiber layer (RNFL). Results: The mean SE was -1.58 ± 3.71 diopters (D). The mean AXL was 18.76 ± 0.86 mm. The prevalence rate of high myopia was 17.7%. As myopia aggravated, the AXL increased (r = -0.498, P < 0.001). Compared with non-high myopia, highly myopic eyes had a greater AXL (P < 0.001), less RNFL thickness (P = 0.004), a higher incidence of PPA (P < 0.001), and elevated grades of fundus tessellation (P < 0.001). The binary logistic regression was performed, which showed PPA (odds ratio [OR] = 4.924, 95% confidence interval [CI] = 2.375-10.207, P < 0.001) and higher grades of fundus tessellation (OR = 1.865, 95% CI = 1.474-2.361, P < 0.001) were independent risk characteristics for high myopia. Conclusions: In NHPs, a higher grade of fundus tessellation and PPA were significant biomarkers of high myopia. Translational Relevance: The study demonstrates adult NHPs raised in conditioned rooms have a similar prevalence and highly consistent fundus changes with human beings, which strengthens the foundation for utilizing macaques as an animal model in high myopic studies.

Temporal trends in the visual impairment burden attributable to high fasting plasma glucose levels: a population-based study.

AIMS: Elevated fasting plasma glucose (FPG) levels have been associated with visual impairment. Recognising global patterns of high FPG level exposure can facilitate the prevention and treatment of related visual impairment. We aimed to assess the trends of the visual impairment burden attributable to high FPG levels globally, regionally, nationally, and by income level. METHODS: We obtained data on the visual impairment burden attributable to high FPG levels from the Global Burden of Disease Study 2019. We evaluated the trends of related disability-adjusted life-years (DALYs) from 1990 to 2019 through joinpoint regression analysis and calculated the annual percentage change (APC) and average APC (AAPC). Countries/territories were categorised into high-, upper-middle-, lower-middle-, and low-income groups based on the 2019 World Bank criteria. RESULTS: The age-standardised rate of DALYs due to visual impairment attributable to high FPG levels significantly increased globally, from 6.75 (95% uncertainty interval [UI], 1.55-15.79) in 1990 to 8.44 per 100,000 population (95% UI, 2.00-19.63) in 2019 (AAPC, 0.79; 95% confidence interval [CI], 0.69-0.89; p < 0.001). The largest increases were observed in high-income (AAPC, 0.73; 95% CI, 0.60-0.85) and lower-middle-income countries/territories (AAPC, 0.68; 95% CI, 0.62-0.73). In 2019, lower-middle-income countries/territories had the highest age-standardised DALY rate (18.94 per 100,000 population; 95% UI, 4.39-43.98), whereas high-income countries/territories had the lowest (2.97 per 100,000 population; 95% UI, 0.75-6.74). CONCLUSIONS: The visual impairment burden associated with elevated FPG levels has increased significantly, necessitating enhanced public health prevention measures, clinical management, and treatment to mitigate adverse outcomes.

Quantitative Assessment of Fundus Tessellated Density in Highly Myopic Glaucoma Using Deep Learning.

Purpose: To characterize the fundus tessellated density (FTD) in highly myopic glaucoma (HMG) and high myopia (HM) for discovering early signs and diagnostic markers. Methods: This retrospective cross-sectional study included hospital in-patients with HM (133 eyes) and HMG (73 eyes) with an axial length ≥26 mm at Zhongshan Ophthalmic Center. Using deep learning, FTD was quantified as the average exposed choroid area per unit area on fundus photographs in the global, macular, and disc regions. FTD-associated factors were assessed using partial correlation. Diagnostic efficacy was analyzed using the area under the curve (AUC). Results: HMG patients had lower global (0.20 ± 0.12 versus 0.36 ± 0.09) and macular FTD (0.25 ± 0.14 vs. 0.40 ± 0.09) but larger disc FTD (0.24 ± 0.11 vs. 0.19 ± 0.07) than HM patients in the tessellated fundus (all P < 0.001). In the macular region, nasal FTD was lowest in the HM (0.26 ± 0.13) but highest in the HMG (0.32 ± 0.13) compared with the superior, inferior, and temporal subregions (all P < 0.05). A fundus with a macular region nasal/temporal (NT) FTD ratio > 0.96 (AUC = 0.909) was 15.7 times more indicative of HMG than HM. A higher macular region NT ratio with a lower horizontal parapapillary atrophy/disc ratio indicated a higher possibility of HMG than HM (AUC = 0.932). Conclusions: FTD differs in degree and distribution between HMG and HM. A higher macular NT alone or with a lower horizontal parapapillary atrophy/disc ratio may help differentiate HMG. Translational Relevance: Deep learning-based FTD measurement could potentially assist glaucoma diagnosis in HM.

Age-period-cohort analysis of the global burden of visual impairment according to major causes: an analysis of the Global Burden of Disease Study 2019.

BACKGROUND: Cataract, glaucoma and age-related macular degeneration (AMD) are major causes of visual impairment. As these are age-related conditions, the prevalence of associated visual impairment is anticipated to increase as the population ages. However, age-period-cohort effects on the disease burden have not been investigated. METHODS: This was a population-based study using aggregated data from the Global Burden of Disease Study 2019. Age-period-cohort analysis was conducted using age-standardised prevalence rates (ASPRs) of visual impairment caused by cataract, glaucoma and AMD as disease burden indicator. RESULTS: In 2019, the estimated global ASPRs of visual impairment due to cataract, glaucoma and AMD were 1207.9, 94.7 and 96.8 per 100 000 people, respectively. Between 1990 and 2019, the global visual impairment ASPRs for glaucoma and AMD declined by 15.4% and 2.0%, respectively, whereas that for cataract increased by 5.0%. Wide heterogeneity was observed in age-period-cohort effects on ASPRs across different Sociodemographic Index (SDI) regions. Low-middle SDI regions had the largest ASPR reductions for all three eye diseases and showed improvement in both period and cohort effects. In contrast, in high-middle SDI regions, visual impairment ASPRs significantly increased during the study period with unfavourable patterns. CONCLUSIONS: The wide heterogeneity in age-period-cohort effects reflects different stages of societal transition and vision health. The unfavourable trends in age-period-cohort effects on disease prevalence identified in specific groups provide key information that may be used to identify priority groups in need of treatment and prevention.

Naked-Eye 3-Dimensional Vision Training for Myopia Control: A Randomized Clinical Trial.

Importance: Early onset of myopia increases the risk of high myopia, which can lead to irreversible retinal damage and even loss of central vision. Objective: To investigate the efficacy and safety of naked-eye 3-dimensional vision training (NVT) in preventing the progression of myopia in children. Design, Setting, and Participants: This randomized clinical trial was conducted in 3 hospitals from May 25, 2022, to February 24, 2023. Participants were children (aged 6-18 years) who had a diagnosis of myopia with a spherical equivalent refraction of -0.75 to -6.00 diopters (D). Intervention: Children in the intervention group received 20 minutes of NVT treatment every day, whereas children in the control group lived as usual without vision training. Main Outcome and Measure: The primary outcome was the change in axial length at 6 months. Spherical equivalent refraction (SER) was included as a secondary outcome. Results: Among 263 participants, 125 (47.5%) were male and 138 (52.5%) were female; the mean (SD) age was 10.3 (1.9) years (range, 6.1-15.6 years). A total of 227 patients (86.3%) completed the 6-month follow-up, including 102 in the intervention group and 125 in the control group. In the intervention group, the changes in axial length and SER at 6 months were 0.18 mm (95% CI, 0.16 to 0.20 mm) and -0.25 D (95% CI, -0.31 to -0.19 D), respectively. In the control group, the changes in axial length and SER at 6 months were 0.23 mm (95% CI, 0.21 to 0.25 mm) and -0.35 D (95% CI, -0.41 to -0.30 D), respectively. The differences in AL and SER between the 2 groups were significant (AL difference: -0.06 mm; 95% CI, -0.09 to -0.03; P < .001; SER difference: 0.10 D; 95% CI, 0.02 to 0.19; P = .02). No study-related adverse reactions were reported during follow-up. Conclusions and Relevance: NVT is a safe and promising means to control myopia progression in children with good adherence. Trial Registration: ClinicalTrials.gov Identifier: NCT05468775.

Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina.

Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment. Through high-throughput single-cell RNA sequencing (scRNA-seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA-seq database of age-related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age-related retinal disorders.

Intracellular Zn2+ promotes extracellular matrix remodeling in dexamethasone-treated trabecular meshwork.

Given the widespread application of glucocorticoids in ophthalmology, the associated elevation of intraocular pressure (IOP) has long been a vexing concern for clinicians, yet the underlying mechanisms remain inconclusive. Much of the discussion focuses on the extracellular matrix (ECM) of trabecular meshwork (TM). It is widely agreed that glucocorticoids impact the expression of matrix metalloproteinases (MMPs), leading to ECM deposition. Since Zn2+ is vital for MMPs, we explored its role in ECM alterations induced by dexamethasone (DEX). Our study revealed that in human TM cells treated with DEX, the level of intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. This correlated with changes in several Zrt-, Irt-related proteins (ZIPs) and metallothionein. ZIP8 knockdown impaired extracellular Zn2+ uptake, but Zn2+ chelation did not affect ZIP8 expression. Resembling DEX's effects, chelation of Zn2+ decreased MMP2 expression, increased the deposition of ECM proteins, and induced structural disarray of ECM. Conversely, supplementation of exogenous Zn2+ in DEX-treated cells ameliorated these outcomes. Notably, dietary zinc supplementation in mice significantly reduced DEX-induced IOP elevation and collagen content in TM, thereby rescuing the visual function of the mice. These findings underscore zinc's pivotal role in ECM regulation, providing a novel perspective on the pathogenesis of glaucoma.NEW & NOTEWORTHY Our study explores zinc's pivotal role in mitigating extracellular matrix dysregulation in the trabecular meshwork and glucocorticoid-induced ocular hypertension. We found that in human trabecular meshwork cells treated with dexamethasone, intracellular Zn2+ significantly decreased, accompanied by impaired extracellular Zn2+ uptake. Zinc supplementation rescues visual function by modulating extracellular matrix proteins and lowering intraocular pressure, offering a direction for further exploration in glaucoma management.

Visual impairment burden in retinopathy of prematurity: trends, inequalities, and improvement gaps.

Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment, and the increase in number and survival of premature infants may inflate its burden globally. We aimed to comprehensively assess the trends and inequalities in the burden of ROP-related visual impairment and to identify improvement gaps to facilitate appropriate actions in neonatal care systems. We obtained ROP data from the Global Burden of Disease 2019 study. We employed joinpoint regression analysis to assess the trends of the burden of ROP-related visual impairment, measured by age-standardised prevalence rates, health equity analysis methods to evaluate cross-country burden inequalities, and data envelopment and stochastic frontier analyses to identify improvement gaps based on the development status, i.e., sociodemographic index (SDI). Between 1990 and 2019, the age-standardised prevalence rates of ROP-related visual impairment significantly increased worldwide (average annual percentage change: 0.23 [95% confidence interval, 0.21-0.26] among males and 0.26 [0.25-0.27] among females), primarily in developed regions. Although significant SDI-related cross-country inequalities were identified, these reduced over time (slope index of inequality: -57.74 [-66.22 to -49.25] in 1990 to -29.68 [-38.39 to -20.97] in 2019; health concentration index: -0.11 [-0.13 to -0.09] in 1990 to -0.07 [-0.09 to -0.06] in 2019). Notably, some less-developed countries exhibited superior performance despite limited resources, whereas others with a higher SDI delivered lagging performance.  Conclusion: The global burden of ROP-related visual impairment has steadily increased between 1990 and 2019, with disproportionate burden concentration among less-developed countries, requiring appropriate preventive and intervention measures. What is Known: • Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment. • The prevalence of ROP is anticipated to increase due to the growing number of extremely premature infants. What is New: • The prevalence of ROP-related visual impairment has increased worldwide, primarily in developed regions, with declining but persisting cross-country inequalities. • The increasing burden of ROP-related visual impairment should be considered as part of global and national health agendas, requiring interventions with proven efficacy.

Single-cell transcriptomic Atlas of aging macaque ocular outflow tissues.

The progressive degradation in the trabecular meshwork (TM) is related to age-related ocular diseases like primary open-angle glaucoma. However, the molecular basis and biological significance of the aging process in TM have not been fully elucidated. Here, we established a dynamic single-cell transcriptomic landscape of aged macaque TM, wherein we classified the outflow tissue into 12 cell subtypes and identified mitochondrial dysfunction as a prominent feature of TM aging. Furthermore, we divided TM cells into 13 clusters and performed an in- depth analysis on cluster 0, which had the highest aging score and the most significant changes in cell proportions between the two groups. Ultimately, we found that the APOE gene was an important differentially expressed gene in cluster 0 during the aging process, highlighting the close relationship between cell migration and extracellular matrix regulation, and TM function. Our work further demonstrated that silencing the APOE gene could increase migration and reduce apoptosis by releasing the inhibition on the PI3K-AKT pathway and downregulating the expression of extracellular matrix components, thereby increasing the aqueous outflow rate and maintaining intraocular pressure within the normal range. Our work provides valuable insights for future clinical diagnosis and treatment of glaucoma.

Lens power, cornea power and association with refractive error in children with moderate to high hyperopia.

OBJECTIVE: This study aimed to profile ocular biometry parameters and predictors of spherical equivalent refraction (SER) among children with moderate to high hyperopia. METHODS: Individuals <18 years of age with moderate to high hyperopia were enrolled from November 2015 to November 2021. Participants underwent a series of comprehensive ocular examinations, and were classified as having low hyperopia, that is, SER +0.5 to < +2.0 D or moderate to high hyperopia, that is, SER ≥ +2.0 D. RESULTS: A total of 459 and 230 eyes with moderate to high hyperopia and low hyperopia, respectively, were included. Moderate to high hyperopic eyes had a shorter axial length, stronger lens power (24.78 ± 5.47 D vs. 18.74 ± 1.63 D, p < 0.001) and weaker corneal power (42.82 ± 1.75 D vs. 43.31 ± 1.55 D, p < 0.001) than low hyperopic eyes. When comparing values before and after 5 years of age, both lens power and axial length differed significantly in the moderate to high hyperopia group, whereas in the low hyperopia group, they only differed significantly after 9 years of age. Lens power was negatively associated with AL in eyes with axial lengths between 20 and 22 mm. A multiple linear regression model which included axial length (standardised ß = -0.80, p < 0.001), corneal power (standardised ß = -0.47, p < 0.001) and lens power (standardised ß = 0.23, p < 0.001) explained 81.2% of the variance in SER. CONCLUSIONS: Differences in lens power and axial length in moderate to high hyperopic eyes became significantly smaller after 5 years of age, at least 4 years earlier than for the low hyperopia. Lens power could offset the axial elongation in participants with axial lengths between 20 and 22 mm, suggesting that children with moderate to high hyperopia might have different ocular growth patterns. Axial length, corneal power and lens power were the main predictors of SER in moderate to high hyperopia.

Temporal trends and projection of blindness and vision loss prevalence in older adults in BRICS countries.

BACKGROUND: Blindness and vision loss (BVL) is a major global health issue affecting older adults, but its burden in transition countries has received limited attention. Therefore, we aimed to assess the trends in the burden of BVL among older adults between 1990 and 2019 across Brazil, Russia, India, China, and South Africa (BRICS), and predict the burden by 2040. METHODS: Data on BVL and its related causes were obtained from the Global Burden of Disease 2019 study. We investigated the temporal trends by calculating the average annual percentage change using joinpoint regression analysis. Subsequently, we performed Bayesian age-period-cohort modeling to estimate the burden of BVL and its related causes by 2040. RESULTS: Most BRICS countries experienced a significant decline (p < 0.05) in age-standardized prevalence rates, and the decreasing trends tend to continue. However, by 2040, the number of BVL cases is expected to increase by approximately 50% across BRICS, with an estimated approximately 192, 170, 25, 17, and 7 million cases in China, India, Russia, Brazil, and South Africa, respectively. The related ranks of BVL causes are also estimated to change in the future, particularly in India. CONCLUSIONS: The different burdens and trends of BVL across BRICS reflected the different stages of population health transition. Effective eye disease prevention requires appropriate public health interventions. Developing effective health policies and services for older adults is urgently needed in BRICS countries.

The associations of self-perception, movement competence, and clinical features of young school-aged children with glaucoma.

The purpose of the study was to determine the associations of self-perception, motor skills, and clinical features of young school-age children with glaucoma (CG). This is a cross-sectional observational study. Children from preschool to second grade, including CG (N = 19), children with amblyopia (CA, N = 28), and controls (N = 32), completed the Manual Dexterity and Aiming and Catching Scales of the Movement Assessment Battery for Children-2nd edition (MABC-2), including Manual Dexterity, Aiming and Catching, and Balance. CG, CA, and their parent completed the Pictorial Scale of Perceived Competence and Social Acceptance for Young Children, respectively, assessing the child's cognitive competence, peer acceptance, physical competence, and maternal acceptance. The Kruskal-Wallis H test and Bonferroni post hoc test compared motor skills among groups. Spearman's correlation analysis evaluated the correlations between motor skills, self-perception, and clinical features. The CG reported lower peer acceptance than CA (P = 0.040), and the parents of CG reported lower cognitive competence than CG reported (P = 0.046). Compared with controls, CG had worse performance of Aiming and Catching, and Balance (P = 0.018 and P = 0.001), and CA had worse performance of Balance (P = 0.009). The motor skills were comparable between CG and CA. For CG, older age correlated with worse competence of Aiming and Catching (r = - 0.620, P = 0.005), better best-corrected visual acuity of better-seeing eye correlated with higher competence of Manual Dexterity and Balance (r = - 0.494, P = 0.032, and r = - 0.516, P = 0.024), and longer duration of glaucoma correlated with worse competence of Manual Dexterity (r = - 0.487, P = 0.034). CONCLUSION:  Glaucoma and amblyopia have significant negative impacts on children's daily motor skills. The acuity of a better-seeing eye is an important factor influencing motor movement. TRIAL REGISTRATION: ClinicalTrials.gov identifier, ChiCTR2100050415. WHAT IS KNOWN: • The state of mental health in early childhood influences the development of their future personality and physical development. The prognosis and management of glaucoma may seriously impair the mental health development of the affected children. However, the exploration of psychological aspects and motor movement of childhood glaucoma was limited. WHAT IS NEW: • Children with glaucoma have impaired motor skills and self-perception development, especially in terms of peer socialization.

Reduced Zn2+ promotes retinal ganglion cells survival and optic nerve regeneration after injury through inhibiting autophagy mediated by ROS/Nrf2.

The molecular mechanism of how reduced mobile zinc (Zn2+) affected retinal ganglion cell (RGC) survival and optic nerve regeneration after optic nerve crush (ONC) injury remains unclear. Here, we used conditionally knocked out ZnT-3 in the amacrine cells (ACs) of mice (CKO) in order to explore the role of reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (NFE2L2, Nrf2) and autophagy in the protection of RGCs and axon regeneration after ONC injury. We found that reduced Zn2+ can promote RGC survival and axonal regeneration by decreasing ROS, activating Nrf2, and inhibiting autophagy. Additionally, autophagy after ONC is regulated by ROS and Nrf2. Visual function in mice after ONC injury was partially recovered through the reduction of Zn2+, achieved by using a Zn2+ specific chelator N,N,N',N'-tetrakis-(2-Pyridylmethyl) ethylenediamine (TPEN) or through CKO mice. Overall, our data reveal the crosstalk between Zn2+, ROS, Nrf2 and autophagy following ONC injury. This study verified that TPEN or knocking out ZnT-3 in ACs is a promising therapeutic option for the treatment of optic nerve damage and elucidated the postsynaptic molecular mechanism of Zn2+-triggered damage to RGCs after ONC injury.

Empagliflozin targets Mfn1 and Opa1 to attenuate microglia-mediated neuroinflammation in retinal ischemia and reperfusion injury.

BACKGROUND: Neuroinflammation and mitochondrial dysfunction play crucial roles in retinal ischemia and reperfusion (IR) injury. Recent studies have identified mitochondrial function as a promising target for immunomodulation. Empagliflozin (EMPA), an anti-diabetic drug, has exhibited great potential as both an anti-inflammatory agent and a protector of mitochondrial health. This study aimed to assess the therapeutic efficacy of EMPA in retinal IR injury. METHODS: To evaluate the protective effects of EMPA, the drug was injected into the vitreous body of mice post-retinal IR. Single-cell RNA sequencing (scRNA-seq) analysis was conducted to uncover the underlying mechanisms, and the results were further validated through in vivo and in vitro experiments. RESULTS: EMPA effectively protected retinal ganglion cells (RGCs) from IR injury by attenuating local retinal inflammation. The scRNA-seq analysis revealed that EMPA downregulated the nucleotide-binding domain and leucine-rich repeat containing protein 3 (NLRP3) signaling pathway and restored mitochondrial dynamics by upregulating the expression of mitochondrial fusion-related genes, Mitofusin 1 (Mfn1) and optic atrophy 1 (Opa1). These findings were further corroborated by Western blotting. In vitro experiments provided additional insights, demonstrating that EMPA suppressed lipopolysaccharide (LPS)-induced cell inflammation and NLRP3 inflammasome activation. Moreover, EMPA enhanced mitochondrial fusion, neutralized mitochondrial reactive oxygen species (mtROS), and restored mitochondrial membrane potential (MMP) in BV2 microglia. Notably, genetic ablation of Mfn1 or Opa1 abolished the anti-inflammatory effects of EMPA. CONCLUSIONS: Our findings highlight the positive contribution of Mfn1 and Opa1 to the anti-inflammatory therapeutic effect of EMPA. By restoring mitochondrial dynamics, EMPA effectively mitigates microglia-mediated neuroinflammation and prevents RGC loss in retinal IR injury.

Discovery of Clinical Manifestations in Spontaneous Glaucoma Suspect Nonhuman Primates.

INTRODUCTION: The primary aim of this study was to assess the longitudinal changes in retinal nerve fiber layer (RNFL) thickness and relative ONH parameters using spectral-domain optical coherence tomography (SD-OCT) in the living eyes of nonhuman primates with spontaneous glaucoma. METHODS: Totally 9 macaque subjects underwent a standard fundus photo and OCT examination, including 3 adult monkeys with stable elevated intraocular pressure (IOP) as the glaucoma suspect group and 6 normal IOP monkeys as the control group. Each eye of primates with IOP measurement was repeated three times. OCT measurements recorded RNFL, Bruch's membrane opening (BMO) minimum rim width (MRW). The follow-up scan of glaucomatous subjects was undergone in 10 months. RESULTS: The mean ages of glaucoma and healthy subjects are 19.33 ± 0.33 and 20.5 ± 1.46 years. Elevated IOP was achieved in three nonhuman primate eyes with an average increase of 10 mm Hg over the study period. Elevated IOP was associated with decreased RNFL thickness in all the regions and decreased RNFL phase retardation in the superior and inferior regions. When averaged over the entire retinal area, only the whole RNFL and temporal regions showed a significant decrease. The mean IPL thicknesses are 87.17 ± 2.15 µm in glaucomatous and 93.33 ± 1.51 µm in healthy eyes (p = 0.03). Lamina cribrosa parameters are measured from the OCT images and showed significant differences between glaucoma primates and normal primates. CONCLUSIONS: Of the measured parameters, decreased RNFL and MRW were correlated with glaucomatous damage. Natural glaucoma primate can be a natural glaucoma model which is closer to glaucoma in humans.

Cell atlas of trabecular meshwork in glaucomatous non-human primates and DEGs related to tissue contract based on single-cell transcriptomics.

As the major channel of aqueous humor outflow, dysfunction of trabecular meshwork (TM) can lead to intraocular pressure elevating, which can trigger primary open-angle glaucoma (POAG). In this study, we use single-cell RNA sequencing (scRNA-seq) technique to build an atlas and further explore the spontaneous POAG and healthy macaques cellular heterogeneity associated with the dysfunction of TM contraction. We built the TM atlas, which identified 14 different cell types. In Beam A, Beam B, Beam C, and smooth muscle cell (SMC) cell types, we first found multiple genes associated with TM contraction (e.g., TPM1, ACTC1, TNNT1), determining their differential expression in the POAG and healthy groups. In addition, the microstructural alterations in TM of POAG non-human primates were observed, which was compact and collapsed. Thus, our study indicated that TPM1 may be a key target for regulating TM structure, contraction function, and resistance of aqueous humor outflow.

Standard ophthalmology residency training in China: an evaluation of resident satisfaction on training program in Guangdong Province.

BACKGROUND: National standardized training for resident doctors (STRD) in mainland China has been formally established since 2014 as a kind of postgraduate education. The purpose of this survey was to assess the satisfaction of the training residents in Guangdong Province on the ophthalmology STRD program after a duration of 5 years. METHOD: A 48-item survey was sent to all postgraduate ophthalmology residents from bases in Guangdong Province to inquire about their attitude towards the program. The survey contained questions about demographic and work-related information, job satisfaction, psychological resilience, and job performance. All responses were verified, and invalid questionnaires were excluded. Statistical analyses were performed using SPSS software version 22.0 (SPSS, Inc., Chicago, IL). Multiple logistic regression analysis was used to evaluate the factors (demographic information, working environment, clinical exposure, supervision and hands-on training opportunities, and involvement in academic activities) impacting the overall satisfaction. P < 0.05 was considered statistically significant. RESULTS: A total of 471/635 (74.17%) valid questionnaires were returned from all the STRD bases of Guangdong Province, which included 38 hospitals. 60.3% of the respondents reported overall satisfaction with their training. The satisfaction with operative teaching (60.7%) was slightly lower than the other settings of teaching experience (above 65%). Meanwhile, the satisfaction on different secessions of operative experience was all below 70%, of which in the areas of cornea and orbit were 55.42% and 57.53%, respectively. Some potential factors were found to affect general satisfaction, including the training grade, marriage, working time, income level, the doctor-patient relationship, family members working as doctors, the time proportion spent on writing medical documents during clinical work, and the frequency of attending academic meetings. Improvement was observed in both performing and reporting clinical examinations in the last year of training in comparison to the first year. Finally, 82.8% of the residents acknowledged this training was helpful for future clinical work. The first five career preferences for residents were cataract (67.1%), refractive surgery (42.3%), vitreo-retina (36.5%), optometry (28.7%), and oculoplastic (27.2%). CONCLUSION: Ophthalmology residents in Guangdong Province expressed comparable satisfaction with the STRD program. To further improve satisfaction, factors such as resident subsidy, harmonious marriage, the patient-doctor relationship, and chances of attending academic conferences should be emphasized.