Altered Retinal Pigment Epithelium Protein Expression Associated With the Progression of Age–Related Macular Degeneration

Abstract

Abstract: : Purpose: Age–related macular degeneration (AMD) is characterized by specific clinical features such as drusen, retinal pigment epithelium (RPE) changes, geographic atrophy, and others. The underlying cellular response has not been fully described but likely involves changes in protein expression during defined stages of the disease process. Our goal is to identify proteins with altered expression that will provide insight into mechanisms involved in AMD. Methods: Human donor eyes obtained from the Minnesota Lions Eye Bank were graded using the Minnesota Grading System (MGS) to determine the level of AMD (Olsen & Feng, IOVS, 2004, 45: 4484–90). After grading, RPE proteins were resolved by 2–D gel electrophoresis and protein expression was quantified by densitometry. Differences between MGS categories were determined using a mixture model ANOVA (n = 7 samples per group). Proteins exhibiting significant changes were identified by MALDI–TOF mass spectrometry. Results: We observed distinct patterns of altered protein expression during the progression of AMD, with some changes apparent at early disease stages and others evident only at late stages. Some changes reflected increased protein expression while others reflected decreased expression. For example, several heat shock proteins decreased in expression with AMD while the expression of select mitochondrial proteins either increased or decreased. Conclusions: The present study identified RPE protein expression changes during the course of AMD. Our results suggest that RPE cells undergo changes in stress response capacity and mitochondrial function in AMD, with potential consequences for RPE and photoreceptor survival. Finally, the MGS allowed us to detect expression changes at different disease stages, including the earliest stage of AMD.

Keywords: proteomics • retinal pigment epithelium • age-related macular degeneration