Prosaposin is a dual-action therapeutic target for vascular stabilization and neuroprotection.

The disruption of vascular homeostasis is a key pathological feature of fundus abnormal vascular diseases, including wet age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. While anti-vascular endothelial growth factor therapies are widely used, many patients exhibit limited or suboptimal responses. Through proteomic analysis of 173 aqueous humor samples from fundus abnormal vascular disease patients, followed by validation in an independent cohort of 70 samples, this study identifies prosaposin as a potential therapeutic candidate. In vitro, prosaposin mitigated endothelial dysfunction and reduced vascular permeability, while in vivo, it demonstrated anti-angiogenic and anti-inflammatory effects comparable to aflibercept, effectively reducing vascular leakage and retinal edema. Additionally, prosaposin provided neuroprotection by preserving photoreceptor cells. These findings highlight the dual role of prosaposin in maintaining vascular homeostasis and protecting neural tissues, suggesting its potential as an alternative treatment for patients unresponsive to anti-vascular endothelial growth factor therapies.