Single Particle Protein Profiling for High Myopic Cataract Lens Capsule Tissue-derived Extracellular Vesicles Reveals Macrophage Involvement and AQP1 Correlation

High myopia stands as the primary cause of blindness globally, with cataract emerging as one of the most prevalent complications. However, the underlying mechanism of high myopic cataract remains unknown. The lens capsule is the basement membrane enclosing the lens. In this study, we hypothesized lens capsule tissue-derived EVs (Ti-EVs) play a vital role in the formation of cataract. Ti-EVs were collected from the lens capsule of high myopic and age-related cataract patients during cataract surgery, and isolated by ExoDisc. Then we performed proximity barcoding assay (PBA) for single EV analysis, which enabled us to identify the alteration of Ti-EV subpopulations associated with high myopic cataract. Our findings revealed a predominant immunity cluster within cataracts, characterized by a significantly higher abundance of macrophage-derived EVs in high myopic cataracts, which strongly correlated with the AQP1 cluster, suggesting a potential interaction between these two components in the progression of high myopic cataract. It was also observed that the eye morphogenesis cluster may also work in concert with AQP1, potentially driving the progression of high myopic cataracts through this pathway. These findings not only shed new light on the underlying mechanisms of high myopic cataract, but also pave the way for the development of novel therapeutic strategies to prevent or treat this devastating condition.