Cytokine Regulation of Photoreceptor Gene Expression

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DESCRIPTION (provided by applicant): Neurological cytokines have shown tremendous therapeutic potential for preventing or delaying blindness. Several of these cytokines stimulate the receptor gp130. Stimulation with either leukemia inhibitory factor (LIF) or ciliary neurotrophic factor (CNTF) has three profound effects on retinal cells: inhibition of differentiation; neuroprotection from retinal degeneration; and reduced light response of photoreceptors. Despite the interest in these effects, little is known about the role of gp130 in normal retinal development or its role in preventing photoreceptor death. In this study we will use tissue specific inactivation of gp130 to address three important questions. 1. What is the role gp130 in normal differentiation of the retina? 2. Is gp130 expression in photoreceptors or Muller cells responsible for neuroprotection and function loss? 3. Is the PI3K/Akt pathway responsible for gp130 induced neuroprotection?