Temporal Analysis of Retinal Gene Expression With Streptozotocin-Induced Diabetes

Abstract

Purpose:: The unique anatomy and physiology of the retina may predispose it to the metabolic stresses of diabetes. In addition to vascular alterations, diabetic retinopathy is characterized by neuroinflammation and neuronal pathophysiology. The aim of this study was to examine the gene expression changes underlying these processes.

Methods:: To examine, on a whole genome scale, changes in retinal gene expression, microarray analysis was conducted on whole retinal RNA from rats 1 and 3 months after streptozotocin (STZ)- induced, experimental Type I diabetes. Quantitative PCR confirmation of array changes took two forms: 1) confirmation from the same samples as the array analysis and, 2) confirmation in a second, independent set of 1 and 3 month animals.

Results:: A number of gene expression differences were found in comparison to age-matched, sodium citrate-injected controls. However, diabetes-induced gene expression profiles at 1 and 3 months demonstrated only moderate overlap. Confirmed array changes were grouped into transcripts relating to: vasculature, neural retina, inflammation, and stress.

Conclusions:: In total, these gene expression alterations suggest a progressive state of vascular permeability, inflammation and cellular stress, and impaired neurotransmission. These confirmed and replicated gene expression changes represent both potential targets for therapeutic intervention and biomarkers of diabetes for future preclinical studies of diabetic retinopathy.

Keywords: retina • gene microarray • diabetic retinopathy