Retinal gene expression shows compartment specific differences in health and disease

In most degenerative eye diseases changes in the expression of specific genes are main contributors to their pathogenesis and progression. The retinal structure containing different compartments prompts the question whether compartment specific genes are involved in vasoregression.

We performed a transcriptional profiling of Polycystic Kidney Disease (PKD2) and Sprague Dawley (SD) rats using Affymetrix GeneChips. Isolated retinas were divided into an inner part, containing the GCL, IPL and INL, and an outer part, containing the ONL, rods and cones. The compartments were separated by Laser Dissection Microscopy. RNA was isolated, amplified and then subjected to profiling using the ArrayStudio software. Sets were analyzed with Ingenuity to allocate the identified genes to signaling pathways.

Overall 4908 transcripts were expressed significantly different between the retinal compartments. In the comparison of PKD2 with SD, 287 transcripts were differently regulated in the outer and 82 in the inner part, e.g. lipocalin-2 specifically expressed in the inner part of PKD2 rats (17.5 fold compared to SD, P < 0.001). The Ingenuity analysis identified the top canonical pathways for each compartment containing acute phase response and complement system components. The mechanistic transcriptomics data interpretation revealed possible upstream regulators responsible for the observed changes including cytokines (e.g. IL-4/TNF-α/IL-1β) and transcription factors (e.g. STAT1/STAT3).

This study clearly demonstrates the huge differences in compartment specific retinal gene expression. Our results elucidate the need for a more differentiated interpretation of gene regulation in eye diseases and demonstrate a method enabling us to identify specific genes as biomarkers for neurovascular interactions.