title: Intravitreal Ciliary Neurotrophic Factor Transiently Improves Cone-Mediated Function in a CNGB3-/- Mouse Model of Achromatopsia.
abstract: OBJECTIVE
  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.affiliation: National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States 3Department of Biotechnology and Applied Clinical Science, University of L'Aquila, L'Aquila, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Marangoni
authors.affiliation: National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Camasamudram
authors.initials: C
authors.lastname: Vijayasarathy
authors.affiliation: National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Bush
authors.affiliation: National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Lisa L
authors.initials: LL
authors.lastname: Wei
authors.affiliation: Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami, Miller School of Medicine, Miami, Florida, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Wen
authors.affiliation: National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland, United States 2National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Sieving
mesh_terms: D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage*; D003117:Color Vision Defects / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D004343:Drug Implants; D004596:Electroretinography; D058449:Intravitreal Injections; D051379:Mice; D008822:Mice, Transgenic; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects* / Q000502:physiology
chemical_list: D020934:Ciliary Neurotrophic Factor; D004343:Drug Implants