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 Scopus citations

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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Keywords

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

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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