Intravitreal ciliary neurotrophic factor transiently improves cone-mediated function in a CNGB3−/− mouse model of achromatopsia

Dario Marangoni, Camasamudram Vijayasarathy, Ronald A. Bush, Lisa L. Wei, Rong Wen, Paul A. Sieving

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Purpose: Ciliary neurotrophic factor (CNTF) was recently shown to augment cone function in CNGB3 mutant achromat dogs. However, testing CNTF-releasing implant in human CNGB3 achromats failed to show benefit. We evaluated the effects of CNTF protein on the retinal function in an additional achromatopsia model, the CNGB3−/− mouse. Methods: Fifty-nine CNGB3−/− mice (postnatal day [PD] ± SD = 30 ± 7) received a unilateral intravitreal injection of 1 or 2 μg CNTF protein, and 15 wild-type (WT) mice (PD = 34 ± 3) received 1 μg CNTF. Retinal function was evaluated by flash ERG and photopic flicker ERG (fERG) at 7 and 14 days after treatment. Results: Seven days post CNTF, the photopic b-wave Vmax was significantly increased in CNGB3−/− mice (P <0.01), whereas it was reduced in WT mice (P <0.05). Ciliary neurotrophic factor significantly increased the amplitude of photopic fERG and the photopic oscillatory potentials (OPs) in CNGB3−/− mice. Ciliary neurotrophic factor did not alter the scotopic a-wave in either CNGB3−/− or WT mice, but it increased the scotopic b-wave k (P <0.01) in CNGB3−/− mice, indicating diminished scotopic sensitivity, and reduced the scotopic b-wave Vmax in WT mice (P <0.05). No difference was found in ERG parameters between 1 or 2 μg CNTF. Fourteen days after CNTF injection the ERG changes in CNGB3−/−mice were lost. Conclusions: Intravitreal bolus CNTF protein caused a small and transient improvement of cone-mediated function in CNGB3−/−mice, whereas it reduced rod-mediated function. The increase in photopic OPs and the lack of changes in scotopic a-wave suggest a CNTF effect on the inner retina.

Original languageEnglish (US)
Pages (from-to)6810-6822
Number of pages13
JournalInvestigative Ophthalmology and Visual Science
Volume56
Issue number11
DOIs
StatePublished - Oct 1 2015

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Color Vision Defects
Ciliary Neurotrophic Factor
Nerve Growth Factors
Intravitreal Injections
Retina

Keywords

  • Achromatopsia
  • CNGB3
  • CNTF
  • Cone photoreceptors
  • Intravitreal injection

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Intravitreal ciliary neurotrophic factor transiently improves cone-mediated function in a CNGB3−/− mouse model of achromatopsia. / Marangoni, Dario; Vijayasarathy, Camasamudram; Bush, Ronald A.; Wei, Lisa L.; Wen, Rong; Sieving, Paul A.

In: Investigative Ophthalmology and Visual Science, Vol. 56, No. 11, 01.10.2015, p. 6810-6822.

Research output: Contribution to journalArticle

Marangoni, Dario ; Vijayasarathy, Camasamudram ; Bush, Ronald A. ; Wei, Lisa L. ; Wen, Rong ; Sieving, Paul A. / Intravitreal ciliary neurotrophic factor transiently improves cone-mediated function in a CNGB3−/− mouse model of achromatopsia. In: Investigative Ophthalmology and Visual Science. 2015 ; Vol. 56, No. 11. pp. 6810-6822.
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AU - Wei, Lisa L.

AU - Wen, Rong

AU - Sieving, Paul A.

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