Potential effects of progranulin and granulins against retinal photoreceptor cell degeneration

PURPOSE: The authors previously reported that progranulin attenuated retinal degeneration. The present study focused on the role of progranulin and its cleavage products, granulins, in the pathogenesis of photoreceptor degeneration. METHODS: Photoreceptor degeneration was induced with excessive exposure of murine photoreceptor cells and the retinas of albino mice to white fluorescent light. Damaged photoreceptor cells and retinas were examined using a cell death assay, western blotting, and immunostaining. RESULTS: Even after proteolytic cleavage, treatment with progranulin or its cleavage products or both exerted protective effects on photoreceptors against light exposure. In the murine retina, the expression levels of granulins and the macrophage and microglia marker Iba-1 were increased at 48 h after light exposure. Additionally, progranulin(+) and Iba-1(+) double-positive cells had accumulated in the outer nuclear layer, the primary location of photoreceptor cells. CONCLUSIONS: These results suggest that progranulin or its cleavage products, granulins, or both may be therapeutic targets for age-related macular degeneration and other neurodegenerative diseases.