Networks modulating the retinal response to injury: Insights from microarrays, expression genetics, and bioinformatics

Abstract

Defining the master regulators of retinal wound-healing response is the holy grail of transcriptome-wide analyses. To predict regulatory networks, we integrated transcriptome-wide changes with genetic linkage analysis and bioinformatics. Our studies yielded three complementary insights. First, groups of functionally related genes underlie the early, delayed, and sustained responses of wound healing. For example, transcriptional factor upregulation define the early response, whereas glial reactive markers and crystallin family upregulation define the sustained response. Second, expression of a subset of neural development, proliferation, and cell survival genes displayed genetic linkage to a locus that includes positional candidate genes Id2 and Lpin1. Third, mice with a nonfunctional Lipin 1 protein displayed increased ganglion cell survival and crystallin expression after optic nerve crush. The Crystallin Network represents one of the first modulatory mechanisms predicted from expression data of injured retina, expression genetics, and bioinformatics. © 2012 Springer Science+Business Media, LLC.