Background: Cataracts now account for the largest proportion of the global burden of blindness and vision loss. Understanding the changing trends in the global burden of cataracts over the past 30 years and the next 15 years is of clear significance for the prevention and control of cataracts in key populations. As far as we know, research on the future burden of cataracts is lacking. Objective: This study aims to assess the global burden of cataracts over the past 30 years by using age-period-cohort modeling and to estimate trends in the next 15 years. Methods: Data were obtained from the Global Burden of Disease Study 2019, the United Nations Development Programme, and the WHO (World Health Organization) Global Health Observatory data repository. The assessment of trends and disparities in the number and rate of disability-adjusted life years (DALYs) for cataracts from 1990 to 2019 was conducted. The association between the age-standardized DALY rate (ASDR) and the socio-demographic index (SDI), human development index (HDI), national levels of particulate matter <2.5 μm in diameter (PM2.5), and ambient ultraviolet radiation (UVR) was determined using linear regression analysis. Additionally, we used the Nordpred (Harald Fekjær and Bjørn Møller) age-period-cohort model to predict the cataract burden from 2020 to 2034. Results: Globally, the number of DALYs due to cataract increased from 3,492,604 (95% uncertainty interval [UI] 2,481,846-4,719,629) in 1990 to 6,676,281 (95% UI 4,761,210-9,006,193) in 2019. The ASDRs due to cataract decreased from 93.17 (95% UI 66.14-125.32) in 1990 to 82.94 (95% UI 59.06-111.75) in 2019, with an average annual percentage change of –0.37 (95% CI –0.44 to –0.3; P<.001). Age, female sex, air pollution, smoking, high fasting plasma glucose levels, and a high body mass index were risk factors for the burden of cataracts. SDI and HDI were negatively correlated with ASDRs of cataracts, while PM2.5 and UVR were positively associated with them. Higher DALY rates were also associated with lower SDI (R2=0.1939; P<.001), lower HDI (R2=0.2828; P<.001), national PM2.5 concentration (R2=0.1874; P<.001), and ambient UVR levels (R2=0.2354; P<.001). The prediction model suggested that the number of DALYs due to cataract will continue to rise globally, while the cataract DALY rate will continue to decrease. Conclusions: While the ASDR of cataracts has decreased, there has been a notable increase in the number of DALYs over the past 30 years. Projections suggest that the global burden of cataracts will continue to rise over the next 15 years. To address this challenge, appropriate prevention and treatment policies must be implemented.

The aim of the present study was to investigate the role of platelet‑derived growth factor (PDGF)‑BB/PDGF receptor (R)‑β signaling in an experimental murine corneal neovascularization (CrNV) model. Experimental CrNV was induced by alkali injury. The intra‑corneal expression of PDGF‑BB was examined using immunohistochemistry. The effect of PDGF‑BB on CrNV was evaluated using immunofluorescence staining. The expression levels of PDGFR‑β in human retinal endothelial cells (HRECs) under normal conditions or following cobalt chloride treatment, which induced hypoxic conditions, was assessed using reverse transcription‑quantitative PCR. The effect of exogenous treatment of PDGF‑BB on the proliferation, migration and tube formation of HRECs under normoxic or hypoxic conditions was evaluated in vitro using Cell Counting Kit‑8, wound healing and 3D Matrigel capillary tube formation assays, respectively. The results indicated that the intra‑corneal expression levels of the proteins of PDGF‑BB and PDGFR‑β were detectable on days 2 and 7 following alkali injury. The treatment with neutralizing anti‑PDGF‑BB antibody resulted in significant inhibition of CrNV. The intra‑corneal expression levels of vascular endothelial growth factor A, matrix metallopeptidase (MMP)‑2 and MMP‑9 proteins were downregulated, while the expression levels of thrombospondin (TSP)‑1, TSP‑2, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)‑1 and ADAMTS‑2 were upregulated significantly in mice treated with anti‑PDGF‑BB antibody. The expression levels of PDGFR‑β were upregulated in HRECs under hypoxic conditions compared with those noted under normoxic conditions. Recombinant human PDGF‑BB promoted the proliferation, migration and tube formation of HRECs under hypoxic conditions. The data indicated that PDGF‑BB/PDGFR‑β signaling was involved in CrNV and that it promoted endothelial cell proliferation, migration and tube formation. The pro‑angiogenic effects of this pathway may be mediated via the induction of pro‑angiogenic cytokine secretion and the suppression of anti‑angiogenic cytokine secretion.

The purpose of this study is to address the effect and mechanism of stromal cell‑derived factor‑1 (SDF‑1)α/chemokine (C‑X‑C motif) receptor 4 (CXCR4) signaling on capillary tube formation of human retinal vascular endothelial cells (HRECs). The expression of CXCR4 in HRECs was quantified by reverse transcription (RT‑PCR) and western blotting. The effects of SDF‑1α/CXCR4 signaling in capillary tube formation and migration of HRECs was examined using three‑dimensional Matrigel assay and wound scratching assay respectively in vitro. Cell proliferation of HRECs was examined using cell counting kit (CCK)‑8 assay in the presence of different concentrations of SDF‑1α protein. The effect of SDF‑1α/CXCR4 signaling in HREC expression of VEGF, basic fibroblast growth factor (bFGF), IL‑8 and intercellular cell adhesion molecule (ICAM)‑1 was examined using RT‑PCR and western blotting. RT‑PCR and western blot analysis revealed CXCR4 was expressed in HRECs. The number of intact capillary tubes formed by HRECs in the presence of SDF‑1α was markedly more compared with a PBS treated control group. However, it was reduced with treatment with an CXCR4 antagonist. Wound scratching assay showed a significant increase in the number of migrated HRECs under SDF‑1α stimulation and the number was reduced with treatment with an CXCR4 antagonist. RT‑PCR and western blotting showed that SDF‑1α significantly promoted VEGF, bFGF, IL‑8 and ICAM‑1 expression in HRECs. The proliferation of HRECs in the presence of SDF‑1α was promoted in a dosage‑dependent manner. SDF‑1α/CXCR4 signaling can increase HREC capillary tube formation through promoting HREC migration, proliferation and expression of VEGF, bFGF, IL‑8 and ICAM‑1.

AIM: To explore the interaction between macrophages and chemokines [monocyte chemoattractant protein 1 (MCP-1/CCL2) and fractalkine/CX3CL1] and the effects of their interaction on neovascularization. METHODS: Human peripheral blood mononuclear cells, donated by healthy volunteers, were separated and cultured in RPMI-1640 medium containing 10% fetal bovine serum, then induced into macrophages by stimulation with 30 mu g/L granulocyte macrophage-colony stimulating factor (GM-CSF). The expression of CCR2 and/or CX3CR1 in the macrophages was examined using flow cytometry. Macrophages were then stimulated with recombinant human CCL2 (rh-CCL2) or recombinant human CX3CL1 (rh-CX3CL1). The expression of angiogenesis-related genes, including VEGF-A, THBS-1 and ADAMTS-1 were examined using real-time quantitative polymerase chain reaction (PCR). Supernatants from stimulated macrophages were used in an assay of human retinal endothelial cell (HREC) proliferation. Finally, stimulated macrophages were co-cultured with HREC in a migration assay. RESULTS: The expression rate of CCR2 in macrophages stimulated by GM-CSF was 42%+/- 1.9%. The expression rate of CX3CR1 was 71%+/- 3.3%. Compared with vehicle-treated groups, gene expression of VEGF-A in the macrophages was greater in 150 mg/L CCL2-treated groups (P<0.05), while expression of THBS-1 and ADAMTS-1 was significantly lower (P<0.05). By contrast, compared with vehicle-treated groups, expression of VEGF-A in 150 mg/L CX3CL1-treated groups was significantly lower (P<0.05), while expression of THBS-1 and ADAMTS-1 was greater (P<0.05). Supernatants from CCL2 treated macrophages promoted proliferation of HREC (P<0.05), while supernatants from CX3CL1-treated macrophages inhibited the proliferation of HREC (P<0.05). HREC migration increased when co-cultured with CCL2-treated macrophages, but decreased with CX3CL1-treated macrophages (P<0.05). CONCLUSION: CCL2 and CX3CL1 exert different effects in regulation of macrophage in expression of angiogenesis-related factors, including VEGF-A, THBS-1 and ADAMTS-1. Our findings suggest that CCL2 and CX3CL1 may be candidate proteins for further exploration of novel targets for treatment of ocular neovascularization.

AIM: To investigate the effects of blockade of insulin receptor substrate-1 (IRS-1) on the bio-function of tube formation of human choroidal endothelial cells (HCECs). METHODS: Quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were performed to determine the expression level of IRS-1 and phospho-IRS-1 in HCECs. Tube formation of HCECs was analyzed using three dimensional in vitro Matrigel assay with or without IRS-1 blockage via IRS-1 inhibitor (GS-101) and vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor. In addition, cell counting kit (CCK)-8 and Transwell migration assay were exerted to analyze the effects of blockade of IRS-1 on the bio-function of proliferation and migration of HCECs, respectively. The apoptosis of HCECs was examined using flow cytometry (FCM). RESULTS: RT-PCR and Western blot revealed that IRS-1 phospho-IRS-1 were expressed in HCECs and the expression level was enhanced by stimulation of VEGF-A. The number of tube formation was decreased significantly in GS-101 treated groups compared to phosphate buffered saline (PBS) treated control groups. Furthermore, both cell proliferation and migration of HCECs were decreased in the presence of GS-101. FCM analysis showed that the apoptosis of HCECs was enhanced when the cells were treated with GS-101. Western blot also showed that the expression level of cleaved-caspase 3 in GS-101 treated group was higher than that in control group. CONCLUSION: Blockade of IRS-1 can inhibit tube formation of HCECs through reducing cell proliferation and migration and promoting cell apoptosis.

To evaluate the safety, tolerability, and preliminary efficacy of a single intravitreal injection of UGX-201, an optogenetic therapy utilizing an adeno-associated virus 2 type 7m8 variant to deliver a recombinant chimeric opsin to retinal ganglion cells, in advanced nonsyndromic retinitis pigmentosa (RP) patients. An investigator-initiated, open-label, nonrandomized, single-center trial (ChiCTR2200062174). Nine patients with advanced nonsyndromic RP were enrolled and stratified into two cohorts by visual function: six with light perception (LP) cohort and three with no LP (NLP) cohort. Single intravitreal injection of UGX-201 at dose of 1.5 × 10¹¹ vg/eye was administered in one eye per participant. All participants were followed up for at least 52 weeks and underwent comprehensive ophthalmic and systemic safety assessments along with visual structure and function examinations. The primary endpoint was safety, including adverse events (AEs), serious AEs, and treatment-related AEs over 52 weeks. Secondary endpoints included changes from baseline in best-corrected visual acuity, full-field stimulus threshold testing, and National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) scores through 52-week follow-up period. No serious ocular or systemic AEs occurred during the 52-week follow-up period. In the LP cohort, mean best-corrected visual acuity in the treated eyes assessed by Freiburg Visual Acuity and Contrast Test showed an improvement of 0.30 logMAR at Week 52. One participant exhibited substantial improvement in full-field stimulus threshold testing. The total composite score of the NEI VFQ-25 in LP cohort increased by 3.72 points at Week 52 from that at baseline. In the NLP cohort, all three participants restored LP in the treated eyes at Week 2, Week 4, and Week 24, respectively. Among them, two still maintained LP at Week 52 (end of study). UGX-201 exhibited a favorable safety profile and was well-tolerated in patients with advanced nonsyndromic RP. Sustained, meaningful visual acuity gains were observed in both LP and NLP cohorts, irrespective of baseline visual function status. These findings underscore the potential of UGX-201 as a first-in-class mutation-independent treatment option for advanced nonsyndromic RP.