Cataract

ObjectiveCataract is the most prevalent cause of blindness. Surgery remains the only effective and widely accepted treatment; early diagnosis and intervention can significantly prevent blindness. Hence,Understanding the current epidemiological status of cataract is crucial for formulating better healthcare policies and effectively preventing blindness due to cataract.DesignThis study utilizes Global burden of Disease (GBD) 2021 data to conduct an in-depth analysis of the burden of cataract from 1990 to 2021, including gender disparities, risk factors, and the relationship between Socio-Demographic index (SDI) and disease burden. Additionally, we performed a frontier analysis of Disability-Adjusted Life Years (DALYs) due to cataract from 1990 to 2021. Finally, we used the BAPC model to project the burden of cataract by gender from 2022 to 2030.ResultsThe study revealed that the global burden of cataract remains significant. Worldwide, the Estimate Annual Percentage Change (EAPC) for cataract prevalence was 0.2117([95% CI] 0.1172-0.3063); the EAPC for cataract DALYs is -0.4798([95%CI] -0.5766--0.3828). Predominantly affecting females, individuals aged 50 and older, and those in medium-low and low SDI regions. Furthermore, the Bayesian Age-Period-Cohort (BAPC) model forecast a gradual decline in the global burden of cataract over the next nine years.ConclusionThis study utilized GBD 2021 to provide an in-depth analysis of the current global disease burden of cataracts. The results showed that although the Age-Standardized Rate (ASR) of DALYs decreased, the overall cataract Number still showed an increasing trend from 1990 to 2021 and 2022-2030.

Cataracts, characterized by the opacification of the eye lens, remain a leading cause of reversible blindness globally. Age and diabetes are key risk factors, and with the increasing aging and diabetic population, the global burden of cataracts is projected to rise significantly. Current treatment is predominantly surgical; however, pharmacological strategies could offer a non-invasive alternative with the potential to delay, prevent, or even reverse cataract progression. Recent research has enhanced our understanding of cataractogenesis, emphasizing oxidative stress as a key underlying mechanism, but also including other processes such as calcium dysregulation and altered lens homeostasis or specific events induced by hyperglycemia in diabetic cataracts. New therapeutic approaches have emerged considering the molecular mechanisms involved in cataracts, most of which focus on pharmacological agents with antioxidant properties. Additionally, small-molecule chaperones, aldose reductase inhibitors, and protein aggregation inhibitors have also demonstrated potential in stabilizing or restoring lens protein structure and transparency. While experimental results have shown encouraging results, further research is needed to optimize drug delivery systems to the lens, assess long-term safety, and confirm the clinical efficacy of these treatments. This article reviews current progress in pharmacological treatments for cataracts, outlining challenges and prospects for future integration into clinical practice.

As a major component of intracellular trafficking, the coat protein complex II (COPII) is indispensable for cellular function during embryonic development and throughout life. The 4 SEC24 proteins (A-D) are essential COPII components involved in cargo selection and packaging. A human disorder corresponding to alterations of SEC24 function is currently known only for SEC24D. Here, we reported that biallelic loss of SEC24C leads to a syndrome characterized by primary microcephaly, brain anomalies, epilepsy, hearing loss, liver dysfunction, anemia, and cataracts in an extended consanguineous family with 4 affected individuals. We showed that knockout of sec24C in zebrafish recapitulated important aspects of the human phenotype. SEC24C-deficient fibroblasts displayed alterations in the expression of several COPII components as well as impaired anterograde trafficking to the Golgi, indicating a severe impact on COPII function. Transcriptome analysis revealed that SEC24C deficiency also affected the proteasome and autophagy pathways. Moreover, a shift in the N-glycosylation pattern and deregulation of the N-glycosylation pathway suggested a possible secondary alteration of protein glycosylation, linking the described disorder with the congenital disorders of glycosylation.

Selenium-independent peroxiredoxin 6 (Prdx6) is a unique member of the peroxiredoxin family, which protects cells from various stressors by regulating reactive oxygen species (ROS) and maintaining survival signaling. As a multifunctional "moonlighting" protein, Prdx6 exhibits glutathione peroxidase (GPx), acidic calcium-independent phospholipase A2, and lysophosphatidylcholine acyltransferase activities, enabling it to reduce ROS. Loss of Prdx6, owing to dysregulation of its transactivator nuclear factor erythroid 2-related factor 2 or aberrant oxidative post-translational modifications from aging or oxidative stress, disrupts cellular homeostasis and triggers inflammatory or non-inflammatory cell death, including apoptosis and pyroptosis. Similar to GPx4, Prdx6 exhibits selenium-independent peroxidase activity and possesses phospholipid hydroperoxide-reducing GPx activity. A novel function of Prdx6 in facilitating selenium utilization was identified recently; that is, it enhances the expression and activity of selenoproteins, especially GPx4, and prevents ferroptosis. Conversely, Prdx6 deficiency reduces selenoprotein levels and promotes ferroptosis. Nevertheless, the molecular mechanisms through which Prdx6 modulates cell death and survival, particularly under aging and oxidative stress conditions contributing to cataractogenesis, remain unclear. In this review, we summarize the current knowledge of Prdx6 regulation and activity during oxidative stress and aging, highlighting its role in inflammatory and non-inflammatory signaling that contributes to eye lens pathology and cataract formation. Additionally, we discuss natural activators and potential therapeutic strategies targeting Prdx6 to extend eye lens health and delay or prevent cataract development. Overall, we conclude that enhancing Prdx6 activity offers a promising strategy to prevent or reverse age-related cataracts.