Proteomic Analysis of Retinas from Two Different Type 1 Diabetic Models

ABSTRACT: Objective To explore the proteomic changes in retina associated with type 1 diabetes mellitus (T1DM) using two different mouse models of diabetic retinopathy (DR). Design Experimental study investigating retinal proteomic changes in Akita and streptozotocin (STZ)-induced diabetic mouse models using mass spectrometry. Subjects/Participants Retinas were obtained from Akita (n=4) and STZ-induced diabetic mice (n=6) 12–16 weeks after diabetes onset and compared with age-matched controls. Methods Quantitative mass spectrometry was performed to identify differentially expressed retinal proteins. Pathway enrichment was analyzed using QIAGEN IPA. Volcano plots with p- and q-value filtering were applied to identify significantly altered proteins. Main Outcome Measures Significantly dysregulated proteins and enriched molecular pathways associated with retinal dysfunction in T1DM, with comparative analysis between Akita and STZ-induced models. Results A total of 224 proteins in Akita mice and 229 proteins in STZ mice were significantly altered compared with controls. Thirty-five proteins in each model showed highly significant changes. Pathway analysis revealed mitochondrial dysfunction, oxidative stress, inflammatory signaling, and endoplasmic reticulum stress responses as key pathways. Comparative analysis suggested that Akita mice develop progressive neurovascular dysfunction, whereas STZ mice exhibit more acute retinal inflammatory responses. Conclusions Experimental diabetic models demonstrate distinctive pattern of retinal protein changes that may explain different patter of DR progression in these models to be considered in experimental studies. Aside from that, the two experiments were conducted in different settings, such differences may stem from the initiating event, such as non–beta cell toxicity in the STZ model or from variations in disease progression. Our study supports those proteomic changes in retina of Akita model is linked to progressive neurovascular damage, while in STZ model it is more linked to acute and aggressive onset of retinal inflammation. Furthermore, there are few common dysregulated proteins in both Akita and STZ models (e.g., HMG box transcription factor BBX and TYW5) are linked to specific signaling pathways (e.g., Wnt/β-catenin / TCF-LEF family signaling and wybutosine modification pathway). These proteins are known to be implicated in the pathogenesis and progression of DR which could be the focus for future studies that may lead to targeted therapies mitigating DR progression.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Retina

DISEASE(S): Type 1 Diabetes Mellitus

SUBMITTER: Paul Stemmer  

LAB HEAD: Mohamed Al-Shabrawey

PROVIDER: PXD069751 | Pride | 2026-10-05

REPOSITORIES: Pride