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Early manifestations and differential gene expression associated with photoreceptor degeneration in Prom1-deficient retina.
- Source :
-
Disease models & mechanisms [Dis Model Mech] 2021 Nov 01; Vol. 14 (11). Date of Electronic Publication: 2021 Nov 24. - Publication Year :
- 2021
-
Abstract
- 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 2 weeks, the expression of several genes was altered at 3 weeks in the Prom1-KO retina, with the expression of 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.<br />Competing Interests: Competing interests The authors declare no competing or financial interests.<br /> (© 2021. Published by The Company of Biologists Ltd.)
Details
- Language :
- English
- ISSN :
- 1754-8411
- Volume :
- 14
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Disease models & mechanisms
- Publication Type :
- Academic Journal
- Accession number :
- 34664634
- Full Text :
- https://doi.org/10.1242/dmm.048962