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

Yiwen Li, Weng Tao, Lingyu Luo, Deqiang Huang, Konrad Kauper, Paul Stabila, Matthew M. Lavail, Alan M. Laties, Rong Wen

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere9495
JournalPLoS One
Volume5
Issue number3
DOIs
StatePublished - Mar 2 2010

Fingerprint

Ciliary Neurotrophic Factor
Retinal Degeneration
neurotrophins
cones (retina)
Cones
Rats
Regeneration
animal models
Retina
Geographic Atrophy
eyes
Transgenic Rats
Peanut Agglutinin
Retinal Cone Photoreceptor Cells
Arrestin
Color Vision
Intravitreal Injections
Retinitis Pigmentosa
Rhodopsin
Macular Degeneration

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration. / Li, Yiwen; Tao, Weng; Luo, Lingyu; Huang, Deqiang; Kauper, Konrad; Stabila, Paul; Lavail, Matthew M.; Laties, Alan M.; Wen, Rong.

In: PLoS One, Vol. 5, No. 3, e9495, 02.03.2010.

Research output: Contribution to journalArticle

Li, Y, Tao, W, Luo, L, Huang, D, Kauper, K, Stabila, P, Lavail, MM, Laties, AM & Wen, R 2010, 'CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration', PLoS One, vol. 5, no. 3, e9495. https://doi.org/10.1371/journal.pone.0009495
Li, Yiwen ; Tao, Weng ; Luo, Lingyu ; Huang, Deqiang ; Kauper, Konrad ; Stabila, Paul ; Lavail, Matthew M. ; Laties, Alan M. ; Wen, Rong. / CNTF induces regeneration of cone outer segments in a rat model of retinal degeneration. In: PLoS One. 2010 ; Vol. 5, No. 3.
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AB - 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.

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