Retinitis pigmentosa (RP) and macular dystrophy (MD) are characterized by gradual photoreceptor death in the retina and are often associated with genetic mutations, including those in the prominin-1 (Prom1) gene.Prom1-knockout (KO) mice recapitulate key features of these diseases including light-dependent retinal degeneration and constriction of retinal blood vessels.The mechanisms underlying such degeneration have remained unclear, however.We here analysed early events associated with retinal degeneration in Prom1-KO mice.We found that photoreceptor cell death and glial cell activation occur between 2 and 3 weeks after birth.
Whereas gene expression was not affected at Ankle Support 2 weeks, the expression of several genes was altered at 3 weeks in the Prom1-KO retina, with the expression of E-Z REST PETS that for endothelin-2 (Edn2) being markedly upregulated.Expression of Edn2 was also induced by light stimulation in Prom1-KO mice reared in the dark.Treatment with endothelin receptor antagonists attenuated photoreceptor cell death, gliosis and retinal vessel stenosis in Prom1-KO mice.Our findings thus reveal early manifestations of retinal degeneration in a model of RP/MD and suggest potential therapeutic agents for these diseases.This article has an associated First Person interview with the first author of the paper.