Abstract
Purpose :
Alzheimer’s disease (AD), age-related macular degeneration (AMD), and diabetic retinopathy demonstrate common pathologies such as the activation of inflammatory processes and disruption of the blood-brain/retina barrier. This study aims to identify specific pathways shared by these three common diseases.
Methods :
Using a proteome approach, we analyzed disease-related proteins via an interaction predictor database followed by a pathway database. AD and AMD proteomics datasets were accessed from the PRIDE data repository (PXD037133: AD n= 8, non-AD controls n= 8 and PXD008354: dry AMD n= 6, wet AMD n= 10, ERM as control n= 9). Vitreous samples from individuals undergoing pars plana vitrectomy for advanced proliferative diabetic retinopathy (DR) were collected and analyzed for proteomics at the Tianjin Medical University Eye Hospital, Tianjin, China (DR n= 12, ERM as control n= 14). Mass spectrometry data were analyzed using Thermo Scientific Xcalibur, and proteins were identified using Proteome Discoverer. MetaboAnalyst was utilized for proteomics statistical analysis to identify disease-related proteins. Disease-associated protein profiles were further analyzed using the STRING database to obtain protein interactomes. Protein-protein interactions were analyzed through the REACTOME database to identify disease-associated pathways.
Results :
STRING analysis revealed protein-protein interaction enrichment in the AD (p= 0.032), AMD (p= 0.042), and DR (p= 0.023). REACTOME pathway analysis of disease associated proteins indicated RUNX2 regulation, and interleukin 1 signaling in AD (p≤0.05), RUNX2 regulation, interleukin 1 signaling, and WNT signaling in AMD (p≤0.05), and regulation of RUNX2 and FLT3, signaling of VEGF, MET, and PDGFR, proteinase activation, and membrane transporter pathways in DR (p≤0.05).
Conclusions :
Using an integrated bioinformatic analysis, we identified that the activation of RUNX2 was common for AD, AMD, and DR. Interleukin 1 signaling pathway was common for AD and AMD. RUNX2 has been implicated in the degradation of the blood-brain/retinal barriers via monocyte activation in DR but has not yet been associated with AD and AMD. RUNX2 pathway modulation may slow the progression or treat AD, AMD, and DR.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.