Retinal Gene Expression Changes Mediated by Leukemia Inhibitory Factor (LIF)

Abstract

Abstract: : Purpose: We have previously found that transgenic expression of LIF blocks the functional maturation of photoreceptors and bipolar neurons through inhibited expression of genes including NRL, opsin, and protein kinase C. The mechanism appears to be mediated through glial cells, suggesting that glial cells may regulate gene expression in retinal neurons. Methods: To investigate the mechanism by which LIF stimulated cells regulate gene expression in retinal neurons, we have adopted DNA microarrays, real-time PCR, and in situ hybridizations to identify genes that are expressed in normal retinas, but that are not expressed in the developmentally-arrested retinas in LIF transgenic mice. Results: The data reveals that many genes that are highly expressed in normal developing retinas are not expressed or are under expressed in the LIF transgenic mice. Our real-time PCR and in situ analysis has confirmed that LIF dramatically inhibits the expression genes in developing retinal neurons, and expression of genes in Muller glial cells. Conclusions: There is significant interest in developing cytokine therapies to prevent or delay retinal degenerations. Members of the interleukin 6 cytokine family, including ciliary neurotrophic factor (CNTF) and LIF have been shown to protect retinal neurons through an unknown mechanism. Based on their function and developmental expression, some of these genes we have identified are likely to play a role in neuronal differentiation as well as a neural protective function.

Keywords: gene microarray • retinal development • animal model