RGD Reference Report - CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration. - Rat Genome Database

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CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration.

Authors: Li, Y  Tao, W  Luo, L  Huang, D  Kauper, K  Stabila, P  LaVail, MM  Laties, AM  Wen, R 
Citation: Li Y, etal., PLoS One. 2010 Mar 2;5(3):e9495.
RGD ID: 6893562
Pubmed: PMID:20209167   (View Abstract at PubMed)
PMCID: PMC2830484   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0009495   (Journal Full-text)

BACKGROUND: Cone photoreceptors are responsible for color and central vision. In the late stage of retinitis pigmentosa and in geographic atrophy associated with age-related macular degeneration, cone degeneration eventually causes loss of central vision. In the present work, we investigated cone degeneration secondary to rod loss in the S334ter-3 transgenic rats carrying the rhodopsin mutation S334ter. METHODOLOGY/PRINCIPAL FINDINGS: Recombinant human ciliary neurotrophic factor (CNTF) was delivered by intravitreal injection to the left eye of an animal, and vehicle to the right eye. Eyes were harvested 10 days after injection. Cone outer segments (COS), and cell bodies were identified by staining with peanut agglutinin and cone arrestin antibodies in whole-mount retinas. For long-term treatment with CNTF, CNTF secreting microdevices were implanted into the left eyes at postnatal day (PD) 20 and control devices into the right eyes. Cone ERG was recorded at PD 160 from implanted animals. Our results demonstrate that an early sign of cone degeneration is the loss of COS, which concentrated in many small areas throughout the retina and is progressive with age. Treatment with CNTF induces regeneration of COS and thus reverses the degeneration process in early stages of cone degeneration. Sustained delivery of CNTF prevents cones from degeneration and helps them to maintain COS and light-sensing function. CONCLUSIONS/SIGNIFICANCE: Loss of COS is an early sign of secondary cone degeneration whereas cell death occurs much later. At early stages, degenerating cones are capable of regenerating outer segments, indicating the reversal of the degenerative process. Sustained delivery of CNTF preserves cone cells and their function. Long-term treatment with CNTF starting at early stages of degeneration could be a viable strategy for preservation of central vision for patients with retinal degenerations.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell body  IDA 6893562 RGD 
photoreceptor outer segment  IDA 6893562; 6893562 RGD 
terminal bouton  IDA 6893562 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Opn1mw  (opsin 1, medium wave sensitive)
Opn1sw  (opsin 1, short wave sensitive)


Additional Information