Growth factor rescue of photoreceptor degeneration in animal models of retinitis pigmentosa

This thesis evaluates the potential of new gene therapies to slow photoreceptor cell death, exhibited by diseases such as retinitis pigmentosa (RP). Human RP patients experience night blindness and progressive vision loss due to photoreceptor cell death. The use of gene therapy to deliver growth factors, such as FGF-2, to the retina shows promise in retarding the progression of the disorder. Sustained expression of these introduced genes occurred through the use of recombinant adeno-associated virus (rAAV) and a ubiquitous cytomegalovirus (CMV) promoter. These studies utilized several rat models, TgN S334ter-4 rhodopsin, TgN P23H-3 rhodopsin, and light damage, all of which mimic the course of various human retinal dystrophies. Viral delivery of FGF-2 provides significant protection from cell death in TgN S334ter-4 rats. This effect was not observed with viral delivery of FGF-2 to TgN P23H and light damage models of photoreceptor degeneration. Two growth factors, FGF-2 and FGF-5, were also delivered to the retina to examine the possible synergistic effects on photoreceptor apoptosis. Variations in rescue effects observed in this thesis reflect the issues that face the use of gene therapy for practical disease applications.