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Early manifestations and differential gene expression associated with photoreceptor degeneration in prom1-deficient retina

Kobayashi, Yuka ; Watanabe, Shizuka ; Ong, Agnes Lee Chen LU orcid ; Shirai, Manabu ; Yamashiro, Chiemi ; Ogata, Tadahiko ; Higashijima, Fumiaki ; Yoshimoto, Takuya ; Hayano, Takahide and Asai, Yoshiyuki , et al. (2021) In DMM Disease Models and Mechanisms 14(11). p.1-11
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
keywords
Endothelin receptor antagonist, Endothelin-2, Glial cell, Photoreceptor, Prominin-1, Retinal degeneration
in
DMM Disease Models and Mechanisms
volume
14
issue
11
article number
dmm048962
pages
1 - 11
publisher
The Company of Biologists Ltd
external identifiers
  • scopus:85121302935
  • pmid:34664634
ISSN
1754-8403
DOI
10.1242/dmm.048962
language
English
LU publication?
no
additional info
Publisher Copyright: © 2021. Published by The Company of Biologists Ltd
id
35f7bf59-5a24-44ca-a340-273528191c50
date added to LUP
2026-01-23 23:28:33
date last changed
2026-01-27 03:55:20
@article{35f7bf59-5a24-44ca-a340-273528191c50,
  abstract     = {{<p>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.</p>}},
  author       = {{Kobayashi, Yuka and Watanabe, Shizuka and Ong, Agnes Lee Chen and Shirai, Manabu and Yamashiro, Chiemi and Ogata, Tadahiko and Higashijima, Fumiaki and Yoshimoto, Takuya and Hayano, Takahide and Asai, Yoshiyuki and Sasai, Noriaki and Kimura, Kazuhiro}},
  issn         = {{1754-8403}},
  keywords     = {{Endothelin receptor antagonist; Endothelin-2; Glial cell; Photoreceptor; Prominin-1; Retinal degeneration}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{1--11}},
  publisher    = {{The Company of Biologists Ltd}},
  series       = {{DMM Disease Models and Mechanisms}},
  title        = {{Early manifestations and differential gene expression associated with photoreceptor degeneration in prom1-deficient retina}},
  url          = {{http://dx.doi.org/10.1242/dmm.048962}},
  doi          = {{10.1242/dmm.048962}},
  volume       = {{14}},
  year         = {{2021}},
}