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 Ins2akita/+ (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 diabetes onset and compared with age-matched controls. Quantitative mass spectrometry identified 7,933 proteins in Akita retinas and 7,399 proteins in STZ retinas. Differentially expressed proteins were identified using adjusted p-values and log₂ fold-change, ranked by Man-hattan distance, and visualized with volcano plots and heatmaps. The top 20 dysregulat-ed proteins in each model were subjected to canonical pathway analysis. Both models demonstrated upregulation of inflammatory and angiogenesis-associated proteins, in-cluding LRRC58, coronin-2A, S100-A4, and COL4A2, supporting a pro-inflammatory and vascular remodeling microenvironment. However, there were distinctive changes in some proteins between the two models. For example, Crystallins were downregulated in the STZ model but upregulated in the Akita model. Canonical pathway analysis revealed ac-tivation 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 can-didate molecular pathways for further investigation and therapeutic targeting.