Genetic evidence and cross-species functional characterization implicate <i> CNN2 </i> in age-related macular degeneration susceptibility

Abstract

Title: Significance Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss among older adults and is projected to affect approximately 288 million people worldwide by 2040. Identifying the genes and cellular mechanisms underlying established AMD risk loci is essential for understanding disease pathogenesis and facilitating therapeutic development. By integrating human genetic analyses with functional studies in zebrafish and mouse models, we identify CNN2 as a compelling candidate AMD gene and demonstrate that CNN2 deficiency disrupts photoreceptor structure and visual function. Our findings support a model in which CNN2 deficiency perturbs retinal neurovascular homeostasis, potentially contributing to photoreceptor dysfunction in AMD.