A systematic proteomic profiling and pathway analysis of protein biomarkers in diabetic retinopathy with subsequent validation of the IL-6 upstream regulator

Purpose Diabetic retinopathy (DR) is a leading cause of irreversible blindness worldwide. Identifying risk factors associated with DR development and progression is crucial for improving treatment efficacy. Although proteomic changes in DR have been extensively studied, the results remain equivocal. Hence, this study aims to summarize and identify potential diagnostic or prognostic markers for DR. In addition, the upstream regulator responsible for protein deregulation of this disease was also validated. Methods We systematically analyzed the current literature on proteomic profile changes in DR, followed by pathway analysis identification. To validate the protein level changes, ELISA was performed from serum samples collected from 27 patients with DR and 25 healthy controls. Results Our analysis revealed that 1 candidate marker (afamin [AFM]) distinguished non-proliferative diabetic retinopathy (NPDR) from type 2 diabetic patients with no diabetic retinopathy/controls, 65 candidate markers distinguished proliferative diabetic retinopathy (PDR) from NPDR, 1 candidate marker (thyroid receptor-interacting protein 11 [TRIP11]) distinguished PDR from PDR-DME/DME, and 3 candidate markers for therapeutic evaluation of PDR. Our results pinpoint that inflammatory response, which IL-6 mainly modulated, is responsible for the changes of proteomic profiles identified in DR. This was also validated by ELISA analysis, indicating that IL-6 could be potentially useful for diagnosing DR. Conclusion We report a comprehensive patient-based proteomic approach to identify potential biomarkers for DR diagnosis, prognosis, and treatment evaluation.