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Endothelin-2-mediated protection of mutant photoreceptors in inherited photoreceptor degeneration.

Publication ,  Journal Article
Bramall, AN; Szego, MJ; Pacione, LR; Chang, I; Diez, E; D'Orleans-Juste, P; Stewart, DJ; Hauswirth, WW; Yanagisawa, M; McInnes, RR
Published in: PLoS One
2013

Expression of the Endothelin-2 (Edn2) mRNA is greatly increased in the photoreceptors (PRs) of mouse models of inherited PR degeneration (IPD). To examine the role of Edn2 in mutant PR survival, we generated Edn2(-/-) mice carrying homozygous Pde6b(rd1) alleles or the Tg(RHO P347S) transgene. In the Edn2(-/-) background, PR survival increased 110% in Pde6b(rd1/rd1) mice at post-natal (PN) day 15, and 60% in Tg(RHO P347S) mice at PN40. In contrast, PR survival was not increased in retinal explants of Pde6b(rd1/rd1) ; Edn2(-/-) mice. This finding, together with systemic abnormalities in Edn2(-/-) mice, suggested that the increased survival of mutant PRs in the Edn2(-/-) background resulted at least partly from the systemic EDN2 loss of function. To examine directly the role of EDN2 in mutant PRs, we used a scAAV5-Edn2 cDNA vector to restore Edn2 expression in Pde6b(rd1/rd1) ; Edn2(-/-) PRs and observed an 18% increase in PR survival at PN14. Importantly, PR survival was also increased after injection of scAAV5-Edn2 into Pde6b(rd1/rd1) retinas, by 31% at PN15. Together, these findings suggest that increased Edn2 expression is protective to mutant PRs. To begin to elucidate Edn2-mediated mechanisms that contribute to PR survival, we used microarray analysis and identified a cohort of 20 genes with >4-fold increased expression in Tg(RHO P347S) retinas, including Fgf2. Notably, increased expression of the FGF2 protein in Tg(RHO P347S) PRs was ablated in Tg(RHO P347S); Edn2(-/-) retinas. Our findings indicate that the increased expression of PR Edn2 increases PR survival, and suggest that the Edn2-dependent increase in PR expression of FGF2 may contribute to the augmented survival.

Duke Scholars

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

2

Start / End Page

e58023

Location

United States

Related Subject Headings

  • Up-Regulation
  • Signal Transduction
  • Rhodopsin
  • Retinal Diseases
  • Retina
  • RNA, Messenger
  • Photoreceptor Cells, Vertebrate
  • Mutation
  • Mice, Transgenic
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
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Bramall, A. N., Szego, M. J., Pacione, L. R., Chang, I., Diez, E., D’Orleans-Juste, P., … McInnes, R. R. (2013). Endothelin-2-mediated protection of mutant photoreceptors in inherited photoreceptor degeneration. PLoS One, 8(2), e58023. https://doi.org/10.1371/journal.pone.0058023
Bramall, Alexa N., Michael J. Szego, Laura R. Pacione, Inik Chang, Eduardo Diez, Pedro D’Orleans-Juste, Duncan J. Stewart, William W. Hauswirth, Masashi Yanagisawa, and Roderick R. McInnes. “Endothelin-2-mediated protection of mutant photoreceptors in inherited photoreceptor degeneration.PLoS One 8, no. 2 (2013): e58023. https://doi.org/10.1371/journal.pone.0058023.
Bramall AN, Szego MJ, Pacione LR, Chang I, Diez E, D’Orleans-Juste P, et al. Endothelin-2-mediated protection of mutant photoreceptors in inherited photoreceptor degeneration. PLoS One. 2013;8(2):e58023.
Bramall, Alexa N., et al. “Endothelin-2-mediated protection of mutant photoreceptors in inherited photoreceptor degeneration.PLoS One, vol. 8, no. 2, 2013, p. e58023. Pubmed, doi:10.1371/journal.pone.0058023.
Bramall AN, Szego MJ, Pacione LR, Chang I, Diez E, D’Orleans-Juste P, Stewart DJ, Hauswirth WW, Yanagisawa M, McInnes RR. Endothelin-2-mediated protection of mutant photoreceptors in inherited photoreceptor degeneration. PLoS One. 2013;8(2):e58023.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

2

Start / End Page

e58023

Location

United States

Related Subject Headings

  • Up-Regulation
  • Signal Transduction
  • Rhodopsin
  • Retinal Diseases
  • Retina
  • RNA, Messenger
  • Photoreceptor Cells, Vertebrate
  • Mutation
  • Mice, Transgenic
  • Mice