PRCD is concentrated at the base of photoreceptor outer segments and is involved in outer segment disc formation
| Autor: | Lital Remez, Ido Perlman, Elisabeth Sehn, Irit Mann, Mariela J. Nevet, Uwe Wolfrum, Tamar Ben-Yosef, Leah Rizel, Gilad Allon |
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| Rok vydání: | 2019 |
| Předmět: |
Retinal degeneration
Male genetic structures Immunoelectron microscopy Retinal Pigment Epithelium Biology Retina chemistry.chemical_compound Mice Phagocytosis Genetics medicine Animals Scotopic vision Outer nuclear layer Eye Proteins Molecular Biology Genetics (clinical) Mice Knockout Retinal Degeneration Membrane Proteins Retinal General Medicine medicine.disease Rod Cell Outer Segment Photoreceptor outer segment eye diseases Cell biology Mice Inbred C57BL medicine.anatomical_structure chemistry Retinal Cone Photoreceptor Cells Female sense organs Cone-Rod Dystrophies Retinitis Pigmentosa Photopic vision Signal Transduction |
| Zdroj: | Human molecular genetics. 28(24) |
| ISSN: | 1460-2083 |
| Popis: | Mutations of the PRCD gene are associated with rod-cone degeneration in both dogs and humans. Prcd is expressed in the mouse eye as early as embryonic day 14. In the adult mouse retina PRCD is expressed in the outer segments of both rod and cone photoreceptors. Immunoelectron microscopy revealed that PRCD is located at the outer segment rim, and that it is highly concentrated at the base of the outer segment. Prcd-knockout mice present with progressive retinal degeneration, starting at 20 weeks of age and onwards. This process is reflected by a significant and progressive reduction of both scotopic and photopic electroretinographic responses, and by thinning of the retina, and specifically of the outer nuclear layer, indicating photoreceptor loss. Electron microscopy revealed severe damage to photoreceptor outer segments, which is associated with immigration of microglia cells to the Prcd-knockout retina, and accumulation of vesicles in the inter-photoreceptor space. Phagocytosis of photoreceptor outer segment discs by the retinal pigmented epithelium is severely reduced. Our data show that Prcd-knockout mice serve as a good model for retinal degeneration caused by PRCD mutations in humans. Our findings in these mice support the involvement of PRCD in outer segment disc formation of both rod and cone photoreceptors. Furthermore, they suggest a feedback mechanism which coordinates the rate of photoreceptor outer segment disc formation, shedding and phagocytosis. This study has important implications for understanding the function of PRCD in the retina, as well as for future development of treatment modalities for PRCD-deficiency in humans. |
| Databáze: | OpenAIRE |
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