Differences in regional
protein expression within the human retina may explain molecular predisposition of specific regions to ophthalmic diseases like
age-related macular degeneration,
cystoid macular edema,
retinitis pigmentosa, and
diabetic retinopathy. To quantify
protein levels in the human retina and identify patterns of differentially-expressed
proteins, we collected foveomacular, juxta-macular, and peripheral retina punch biopsies from healthy donor eyes and analyzed
protein content by liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Protein expression was analyzed with 1-way ANOVA, gene ontology, pathway representation, and network analysis. We identified a mean of 1,974
proteins in the foveomacular retina, 1,999 in the juxta-macular retina, and 1,779 in the peripheral retina. Six hundred ninety-seven differentially-expressed
proteins included those unique to and abundant in each anatomic region.
Proteins with higher expression in each region include:
heat-shock protein 90-alpha (HSP90AA1), and
pyruvate kinase (PKM) in the foveomacular retina;
vimentin (VIM) and
fructose-bisphosphate aldolase C (ALDOC); and
guanine nucleotide-
binding protein subunit beta-1 (GNB1) and
guanine nucleotide-
binding protein subunit alpha-1 (GNAT1) in the peripheral retina. Pathway analysis identified downstream mediators of the
integrin signaling pathway to be highly represented in the foveomacular region (P = 6.48 e-06). Metabolic pathways were differentially expressed among all
retinal regions. Gene ontology analysis showed that
proteins related to
antioxidant activity were higher in the juxta-macular and the peripheral retina, but present in lower amounts in the foveomacular retina. Our proteomic analysis suggests that certain
retinal regions are susceptible to different forms of metabolic and oxidative stress. The findings give mechanistic insight into retina function, reveal important molecular processes, and prioritize new pathways for therapeutic targeting.