Abstract
Previous observational studies have indicated a significant correlation between plasma proteome composition and cataract pathological status; however, the direction of causality remains uncertain. In light of the aforementioned findings, the present study employs a bidirectional two-sample Mendelian randomisation strategy, with the objective of elucidating the direct causal link between plasma proteome changes and cataract development. Following rigorous data analysis and validation, a series of plasma proteins were identified as being strongly associated with cataract risk. These included ILF3, FAM171A1, ARHGEF2, LPR1B, CRYGD, GLT8D1, ARHGEF10 and LRRTM1, all of which were confirmed to be potential risk factors for cataract. In contrast, proteins such as MXRA7, ZHX3, SPAG11B, ARID1A, DNASE1L2, COX7A1 and EEF2K were found to exert a protective effect against cataract. To gain further insight into the specific mechanisms by which these causally related proteins contribute to cataract pathology, we subsequently performed an exhaustive bioinformatics analysis. This analysis not only deepened our understanding of the functional properties of these proteins, but also revealed their possible involvement in signalling pathways and molecular interactions, thereby providing new insights into the pathogenesis of cataract.