Proteomic Analysis of Retinas from Two Different Type-1 Diabetic Models

This study investigated retinal proteomic alterations associated with type-1 diabetes mellitus (T1DM) using two mouse models of diabetic retinopathy (DR): the genetic Ins2^akita/+ (Akita) model and streptozotocin (STZ)-induced diabetes. Retinas were collected from Akita (n = 4) and STZ-induced diabetic mice (n = 6) 15-16 weeks after the onset of diabetes and compared with age-matched controls. Quantitative mass spectrometry identified 7933 proteins in Akita retinas and 7399 proteins in STZ retinas. Differentially expressed proteins were identified using adjusted p-values and log₂ fold-change, ranked by Manhattan distance, and visualized with volcano plots and heatmaps. The top 20 dysregulated proteins in each model were subjected to canonical pathway analysis. Both models demonstrated upregulation of inflammatory and angiogenesis-associated proteins, including LRRC58, coronin-2A, S100-A4, and COL4A2, supporting a pro-inflammatory and vascular remodeling microenvironment. However, several protein changes differed between the two models. For example, Crystallins were downregulated in the STZ model but upregulated in the Akita model, which were validated by western blot analysis. Canonical pathway analysis revealed activation of platelet-related signaling pathways, enrichment of lipid metabolic networks, and significant alterations in extracellular matrix organization. These findings indicate coordinated inflammatory, metabolic, and structural remodeling in DR and identify candidate molecular pathways for further investigation and therapeutic targeting.