Comparative proteomic analysis of human vitreous in rhegmatogenous retinal detachment and diabetic retinopathy reveals a common pathway and potential therapeutic target

Background: The vitreous humor serves as a window into the physiological and pathological processes of the eye, particularly the retina. Diabetic retinopathy (DR), a leading cause of blindness, involves hyperglycemia-induced damage to retinal cells, leading to ischemia and elevated nitric oxide levels, culminating in vascular proliferation. Rhegmatogenous retinal detachment (RD) results from a break in the neuroretina, triggering ischemia, photoreceptor death, and cellular proliferation. Proliferative vitreoretinopathy (PVR) further complicates these conditions through fibrous proliferation. Despite their prevalence and potential for blindness, our understanding of the molecular mechanisms underlying these vitreoretinal diseases is incomplete. Methods and results: To elucidate disease mechanisms and identify potential therapeutic targets, we conducted a comparative proteomic analysis of vitreous samples from DR, RD, and macular pucker (P) patients, which were chosen as controls. LC-MS analysis identified 988 quantifiable proteins, with distinct clustering observed among disease groups. Differential expression analysis revealed 202 proteins in RD vs. P and 167 in DR vs. P, highlighting distinct proteomic signatures. Enrichment analysis identified glucose metabolism as an altered process in both diseases, suggesting common pathways despite differing etiologies. Notably, aldo-keto reductase family 1 member B1 (AKR1B1) has emerged as a potential key player in both DR and RD, indicating its role in glucose metabolism and inflammation. In silico drug screening identified diclofenac, an approved ophthalmic non-steroidal anti-inflammatory drug (NSAID), as a potential therapeutic agent targeting AKR1B1. Conclusion: Our study revealed distinct proteomic signatures and common pathways in vitreoretinal diseases, highlighting AKR1B1 as a potential therapeutic target. Using diclofenac during diagnosis and postoperative care for diabetic retinopathy or rhegmatogenous retinal detachment may reduce complications, lower costs, and improve quality of life. Future research will focus on confirming AKR1B1's role in vitreoretinal diseases and understanding diclofenac's mechanism of action.