Systems Biology of Age-Related Macular Degeneration

Abstract

Purpose:: Age-related macular degeneration (AMD) is a progressive multifactorial degenerative disorder affecting the retina, retinal pigment epithelium (RPE) and choriocapillaries. We investigate this complex disease by using a systems biology approach that includes functional proteomics, bioinformatics and organic synthesis to integrate different levels of information on AMD.

Methods:: First, to gain understanding of the steps involved in the retinoid cycle, proteins from murine, bovine, and zebrafish were used to investigate the proteomics of the visual cycle. We then defined more natural and accurate protein-protein interactions that incorporate more global properties of the network in AMD by the use of new bioinformatics algorithms. Differential 2D-gel electrophoresis and mass spectrometry are used to identify additional target proteins of AMD focusing on 11-cis-retinoid binding proteins, angiogenic factors and neuroprotecting factors. Mapping of proteome and their post-translational modifications were conducted physically and quantitatively to identify spatial and temporal network of signal transduction in AMD.

Results:: In our examinations, we uncovered six primary aspects of the retinoid cycle related with AMD; 11-cis-Retinoid Binding Proteins in the Retinal Pigment Epithelium, existence of visual cycle specific protein complex p175, indirect protein-protein interaction predictions in the retina and RPE, new retinoid isomerase candidate, new inhibitors of visual cycle, and new molecular target for AMD.

Conclusions:: The interdisciplinary systems biology approach to AMD provides new therapeutic implications to prevent blindness and to preserve vision.

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