Expression of neurturin, glial cell line-derived neurotrophic factor, and their receptor components in light-induced retinal degeneration.

ABSTRACT

PURPOSE: Dysregulation of neurturin (NTN) expression has been linked to photoreceptor apoptosis in a mouse model of inherited retinal degeneration. To investigate the extent to which any such dysregulation depends on the nature of the apoptotic trigger, the expression of NTN, glial cell line-derived neurotrophic factor (GDNF), and their corresponding receptor components were compared in a rat model of light-induced retinal degeneration. METHODS: Retinal expression of NTN, GDNF, their corresponding receptors GFRalpha-2 and -1, the transmembrane receptor tyrosine kinase (Ret), and cSrc-p60, a member of the cytoplasmic protein-tyrosine kinases family, were analyzed by Western blot analysis and immunocytochemistry in cyclic light- and dark-reared rats in the presence and absence of intense light exposure. RESULTS: All components for NTN-mediated signaling activation are present in rat photoreceptors and retinal pigment epithelium, the cells primarily affected by light-induced damage. The expression levels of GDNF, its receptor components, and NTN, were not affected by light-induced stress. However, GFRalpha-2 expression strikingly increased with the extent of retinal damage, especially at the photoreceptors, in contrast to decreased levels that were observed previously in an inherited degeneration model. CONCLUSIONS: The present study indicates that the expression of receptors of the GDNF family is independently regulated in normal and light-damaged rat retina, and in conjunction with previous work, suggests that the pattern of modulation of these genes during photoreceptor degeneration is determined by the nature of the apoptotic trigger. Such differential responses to different modes of retinal degeneration may reflect influences of the neurotrophic system on photoreceptor survival or in the regulation of neuronal plasticity.