Abstract
Purpose :
Diabetic macular edema (DME) stands as the leading cause of vision loss in diabetic patients. Despite the widespread utilization of intravitreal anti-vascular endothelial growth factor (VEGF) therapies, the response to treatment varies widely. Our study's primary objective is to identify the molecular markers present in tears of individuals with DME.
Methods :
Tears were collected from 16 normal subjects, 9 diabetic patients with DME, and 36 diabetic patients without DME (spanning severity of diabetic retinopathy), along with corresponding ocular examination results. Tandem mass tag (TMT)-labeled liquid chromatography mass spectrometry (LC-MS/MS) was performed and MaxQuant was used for the tear proteins identification and quantification. Data was analyzed by R (version 4.3.1). Gene set enrichment analysis (GSEA) was used for the analysis of differentially expressed proteins (DEPs) and associated gene sets.
Results :
In our tear proteomic analysis, we identified a total of 2675 proteins. DEPs revealed that proteins associated with angiogenesis, extracellular matrix, and inflammation were significantly altered in DR and correlated with its severity. Furthermore, proteins related to retinal homeostasis were notably reduced in the DME group. Specifically, in DME, MMP9 (log2FC 1.89, p-value 0.001) was upregulated, suggesting its role in extracellular matrix degradation, while RARRES1 (log2FC 1.81, p-value 0.0001) may promote inflammation and fibrosis via the Nuclear Factor-κB signaling pathway.
In addition to the top DEPs identified by the volcano plot, a comprehensive analysis using GSEA revealed that DME patients exhibited enrichment in Sema4D-induced cell migration and growth cone collapse (FDR 0.159, p-value 0.014, NES 1.528). Conversely, negative enrichment was observed in the visual transduction pathway (FDR 0.67, p-value 0.108, NES -1.508).
Conclusions :
Our study highlights the effectiveness of tear proteomic analysis in DME, yielding results comparable to aqueous and vitreous proteomes. Tear proteomes could be used as a surrogate for intraocular samples in the investigation of machanism for DR and DME.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.