Abstract
Purpose :
Proteome studies of the aqueous humor in diabetic macular edema (DME) may bring novel insights to molecular mechanisms underlying the complication.
Methods :
Aqueous humor samples from treatment naïve patients with clinically significant DME (n = 13) and age-matched controls (n = 11) were donated from Department of Ophthalmology, Kyoto Prefectural University of Medicine. BCVA was measured as LogMAR and the severity of DME was measured as central subfield thickness (CST) with OCT. Control samples were obtained prior to cataract surgery. DME and control samples were compared with proteomic analysis by label-free quantification nano liquid chromatography - tandem mass spectrometry. Correction for multiple hypothesis testing was performed with a permutation-based calculation with a false discovery rate at 0.05.
Results :
In DME, 101 proteins were differentially expressed. DME was associated with increased levels of proteins involved in monocyte recruitment, complement activation, coagulation, hemopexin signaling, and kallikrein-kinin signaling. A multitude of proteins involved in glycolysis, VEGF signaling, and HIF-1 signaling were regulated in DME. A loss of extracellular basal membrane proteins was observed in DME. Proteins involved in monocyte recruitment, complement activation and coagulation correlated with BCVA and CST. Proteins involved in insulin homeostatis, desmosomal integrity and adhesion were downregulated in DME and correlated negatively with the severity of DME.
Conclusions :
Multiple proteins correlated with BCVA and the severity of DME, supporting a multifactorial pathogenesis. The discovery of novel proteins involved in the formation of DME may potentially lead to important therapeutic advances.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.