Although occasionally observed in ciliopathy, the consequences of neuronal death and the functional role of neurons in vessel survival and physiology following photoreceptor damage are largely unknown. Using a transgenic rat with overexpression of the mutant cilia gene polycystin-2, we sought to investigate the spatial and temporal development of neuronal degeneration and its functional consequences on the mature retinal vasculature. We used quantitative retinal morphometry, markers of apoptosis, electroretinogram, and expression analysis of neurotrophic and angiogenic growth factors. To this end,TH-302 we established a clear temporal relationship between neuronal degeneration, glial activation and vessel regression and found a predominance of neurotrophic factor activation. To determine whether retinal degeneration is a result of neuronal apoptosis, TGR retinas at 1, 2, 3, 5 and 7 months were evaluated using terminal transferase dUTP nick-end labeling as described in materials and methods. As shown in Fig. 2, apoptotic cells were detected in the outer nuclear layer of TGR retinas,Tofacitinib but no apoptotic cells were recognized in SD control retinas. The onset of apoptosis was observed during the first month of age and increased over time achieving a maximum at 3 months. There were a few apoptotic cells observed in the outer nuclear layer of the TGR retinas at 5 and 7 months of age. The localization and abundance of apoptotic cells in the TGR retinas from 1 to 7 months suggest that neuronal degeneration in TGR retinas is the result of increasing apoptosis in the photoreceptor cells where cilia protein is defective in TGR retinas. To assess alterations in retinal neuronal function of TGR rats, flash ERGs were recorded from 1-, 2-and 3-month-old TGR and SD rats under scotopic and photopic conditions. Under both conditions, retinal functions were normal in TGR rats at the age of 1 month despite the incipience of apoptotic neural cell loss described above. However, 2-month-old TGR rats showed a considerable reduction in amplitudes of both scotopic and photopic ERG responses, indicating alterations of both rod and cone system.