Proteomic and Inflammatory Profile of Aqueous Humor at Different Stages of Diabetic Retinopathy: Identification of Potential Biomarkers
Diabetic Retinopathy; Aqueous Humor; Proteomics; Mass Spectrometry; Biomarkers; Cytokines.
Diabetic Retinopathy (DR) is the leading cause of irreversible blindness in working-age adults, with a pathophysiology that has evolved from classic microvascular damage to a complex paradigm of retinal Neurovascular Unit (NVU) dysfunction. Mechanisms such as mitochondrial stress, neuroinflammation, dysregulation of the VEGF/Angiopoietin-2 pathways, senescence, and NLRP3 inflammasome-mediated pyroptosis drive tissue injury, necessitating novel molecular biomarkers. This real-world study aims to map global proteomic profiles and inflammatory cytokines in the aqueous humor (AH) of 60 eyes (20 Controls, 20 Non-Proliferative DR [NPDR], and 20 Proliferative DR [PDR]), correlating molecular findings with best-corrected visual acuity (BCVA) and spectraldomain optical coherence tomography (SD-OCT) parameters. AH aliquots (100 µL) will be analyzed using untargeted mass spectrometry (LC-MS/MS) and a Luminex multiplex immunoassay to validate key cytokines, accompanied by bioinformatics analysis via Metascape. AH sampling seeks to evaluate functional (BCVA) and structural SD-OCT alterations, such as macular edema (CRT), EZ/ELM disruption, DRILL, and hyperreflective foci (HRF). It is expected that intraocular liquid biopsy through proteomics and cytokine profiling will identify promising translational biomarkers for early detection, monitoring of response to anti-VEGF therapy, and the advancement of precision ophthalmology.