Factors influencing rod photoreceptor differentiation in the mouse retina: a focus on insulin-like growth factor 1

Hecker, Laura
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Previous studies have identified several genes important in rod genesis, however, there is little information on how these genes are regulated during development. The purpose of this dissertation is to identify and investigate factors influencing rod photoreceptor differentiation. Using high throughput gene and protein expression data we have identified several factors as good candidates for involvement in rod photoreceptor development. We are specifically investigating insulin-like growth factor 1 (IGF-1) and how it affects the molecular network controlling rod photoreceptor differentiation.;IGF-1 is a growth factor present in the developing retina and has previously been shown to influence proliferation, differentiation, and survival of retinal neurons. We characterized IGF-1 receptor expression in developing and mature rod photoreceptors using immunohistochemical methods. IGF-1 receptor immunoreactivity was detected in the outer neuroblastic layer in the embryonic retina and in developing and mature rods in postnatal and adult mice. Using a serum free retinal explant culture system we have investigated the effects of long term exposure to IGF-1 on E17 and P0 mouse retinas. Application of exogenous IGF-1 significantly increased rhodopsin expression at both time points. Thus we have demonstrated a specific role for IGF-1 in promoting rod photoreceptor differentiation. In addition we have shown that IGF-1 acts through a MAP kinase independent pathway to mediate the increase in rods. Our studies are the first to demonstrate a role for IGF-1 in rod photoreceptor differentiation in the murine retina.