Comparative Proteomic Analysis of Type 2 Diabetic versus Non-Diabetic Vitreous Fluids

Author:

Alanazi Abdulaziz H.123,Shan Shengshuai12ORCID,Narayanan S. Priya12ORCID,Somanath Payaningal R.12ORCID

Affiliation:

1. Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USA

2. Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA

3. Department of Clinical Practice, College of Pharmacy, Northern Border University, Rafha 91531, Saudi Arabia

Abstract

Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with complex mechanisms. The study aimed to comprehensively explore vitreous humor of diabetic and non-diabetic individuals, paving the way for identifying the potential molecular mechanisms underlying DR. Methods: Vitreous samples from type 2 diabetic and non-diabetic subjects, collected post-mortem, were analyzed using liquid chromatography–mass spectrometry. Pathway enrichment and gene ontology analyses were conducted to identify dysregulated pathways and characterize protein functions. Results: Pathway analysis revealed dysregulation in multiple metabolic and signaling pathways associated with diabetes, including glycerolipid metabolism, histidine metabolism, and Wnt signaling. Gene ontology analysis identified proteins involved in inflammation, immune response dysregulation, and calcium signaling. Notably, proteins such as Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2), Calcium homeostasis endoplasmic reticulum protein (CHERP), and Coronin-1A (CORO1A) were markedly upregulated in diabetic vitreous, implicating aberrant calcium signaling, inflammatory responses, and cytoskeletal reorganization in DR. Conclusions: Our study provides valuable insights into the intricate mechanisms underlying DR and highlights the significance of inflammation, immune dysregulation, and metabolic disturbances in disease progression. Identification of specific proteins as potential biomarkers underscores the multifactorial nature of DR. Future research in this area is vital for advancing therapeutic interventions and translating findings into clinical practice.

Funder

National Institutes of Health

National Center for Advancing Translational Sciences

Publisher

MDPI AG

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