Intravitreal Ciliary Neurotrophic Factor Transiently Improves Cone-Mediated Function in a CNGB3-/- Mouse Model of Achromatopsia.

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.

• Authors: Dario Marangoni, Camasamudram Vijayasarathy, Ronald A Bush, Lisa L Wei, Rong Wen, Paul A Sieving
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 56 Issue 11 Pg. 6810-22 (Oct 2015) ISSN: 1552-5783 [Electronic] United States
• PMID: 26567794 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Ciliary Neurotrophic Factor
• Drug Implants

Topics

• Animals
• Ciliary Neurotrophic Factor (administration & dosage)
• Color Vision Defects (drug therapy, physiopathology)
• Disease Models, Animal
• Drug Implants
• Electroretinography
• Intravitreal Injections
• Mice
• Mice, Transgenic
• Retinal Cone Photoreceptor Cells (drug effects, physiology)