Glial cell line derived neurotrophic factor delays photoreceptor degeneration in a transgenic rat model of retinitis pigmentosa

We designed experiments to evaluate the therapeutic potential of glial cell line derived neurotrophic factor (GDNF) to rescue photoreceptors from gene tically determined cell death. Gene transfer of the neurotrophic factor to the retina was achieved via a recombinant adeno-associated virus (rAAV) vec tor containing the chicken beta -actin promoter/immediate early cytomegalov irus enhancer (CBA) driving the human GDNF gene. We delivered AAV-CBA-GDNF to the retinas of an animal model of retinitis pigmentosa, the TgN S334ter- 4 rhodopsin line of transgenic rats. Immunohistochemical studies localized AAV-CBA-GDNF-derived recombinant protein to cell bodies, inner segments, an d outer segments of photoreceptor cells as well as to retinal pigment epith elial cells. We assessed the effect of viral delivery by morphometric and e lectroretinographic analysis. These experiments showed that GDNF vector tre atment leads to increased rod photoreceptor survival as indicated by morpho metric analysis of outer nuclear layer thickness. AAV-CBA-GDNF-treated reti nas also demonstrated functional improvement by the substantially increased amplitude of electroretinograms. AAV-CBA-GDNF delivery had a significant r escue effect on photoreceptor degeneration in this animal model.