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Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons.

Publication ,  Journal Article
Cho, K-I; Yi, H; Yeh, A; Tserentsoodol, N; Cuadrado, L; Searle, K; Hao, Y; Ferreira, PA
Published in: Cell Death Differ
February 2009

Prolonged light exposure is a determinant factor in inducing neurodegeneration of photoreceptors by apoptosis. Yet, the molecular bases of the pathways and components triggering this cell death event are elusive. Here, we reveal a prominent age-dependent increase in the susceptibility of photoreceptor neurons to undergo apoptosis under light in a mouse model. This is accompanied by light-induced subcellular changes of photoreceptors, such as dilation of the disks at the tip of the outer segments, prominent vesiculation of nascent disks, and autophagy of mitochondria into large multilamellar bodies. Notably, haploinsufficiency of Ran-binding protein-2 (RanBP2) suppresses apoptosis and most facets of membrane dysgenesis observed with age upon light-elicited stress. RanBP2 haploinsufficiency promotes decreased levels of free fatty acids in the retina independent of light exposure and turns the mice refractory to weight gain on a high-fat diet, whereas light promotes an increase in hydrogen peroxide regardless of the genotype. These studies demonstrate the presence of age-dependent and RanBP2-mediated pathways modulating membrane biogenesis of the outer segments and light-elicited neurodegeneration of photoreceptors. Furthermore, the findings support a mechanism whereby the RanBP2-dependent production of free fatty acids, metabolites thereof or the modulation of a cofactor dependent on any of these, promote apoptosis of photoreceptors in concert with the light-stimulated production of reactive oxygen species.

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Published In

Cell Death Differ

DOI

EISSN

1476-5403

Publication Date

February 2009

Volume

16

Issue

2

Start / End Page

287 / 297

Location

England

Related Subject Headings

  • Retinal Degeneration
  • Reactive Oxygen Species
  • Photoreceptor Cells, Vertebrate
  • Nuclear Pore Complex Proteins
  • Molecular Chaperones
  • Mice, Transgenic
  • Mice
  • Light
  • Hydrogen Peroxide
  • Fatty Acids
 

Citation

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Cho, K.-I., Yi, H., Yeh, A., Tserentsoodol, N., Cuadrado, L., Searle, K., … Ferreira, P. A. (2009). Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons. Cell Death Differ, 16(2), 287–297. https://doi.org/10.1038/cdd.2008.153
Cho, K-in, H. Yi, A. Yeh, N. Tserentsoodol, L. Cuadrado, K. Searle, Y. Hao, and P. A. Ferreira. “Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons.Cell Death Differ 16, no. 2 (February 2009): 287–97. https://doi.org/10.1038/cdd.2008.153.
Cho K-I, Yi H, Yeh A, Tserentsoodol N, Cuadrado L, Searle K, et al. Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons. Cell Death Differ. 2009 Feb;16(2):287–97.
Cho, K-in, et al. “Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons.Cell Death Differ, vol. 16, no. 2, Feb. 2009, pp. 287–97. Pubmed, doi:10.1038/cdd.2008.153.
Cho K-I, Yi H, Yeh A, Tserentsoodol N, Cuadrado L, Searle K, Hao Y, Ferreira PA. Haploinsufficiency of RanBP2 is neuroprotective against light-elicited and age-dependent degeneration of photoreceptor neurons. Cell Death Differ. 2009 Feb;16(2):287–297.

Published In

Cell Death Differ

DOI

EISSN

1476-5403

Publication Date

February 2009

Volume

16

Issue

2

Start / End Page

287 / 297

Location

England

Related Subject Headings

  • Retinal Degeneration
  • Reactive Oxygen Species
  • Photoreceptor Cells, Vertebrate
  • Nuclear Pore Complex Proteins
  • Molecular Chaperones
  • Mice, Transgenic
  • Mice
  • Light
  • Hydrogen Peroxide
  • Fatty Acids