Intravitreal Ciliary Neurotrophic Factor Transiently Improves Cone-Mediated Function in a CNGB3-/- Mouse Model of Achromatopsia
| Autor: | Marangoni, Dario, Vijayasarathy, Camasamudram, Bush, Ronald A, Wei, Lisa L, Wen, Rong, Sieving, Paul A |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Drug Implants
Aging Animal CNGB3 Neurosciences intravitreal injection cone photoreceptors Color Vision Defects Biological Sciences Ophthalmology & Optometry Medical and Health Sciences Transgenic Mice Disease Models Intravitreal Injections Electroretinography Retinal Cone Photoreceptor Cells CNTF Animals Ciliary Neurotrophic Factor achromatopsia Eye Disease and Disorders of Vision |
| Zdroj: | Investigative ophthalmology & visual science, vol 56, iss 11 |
| Popis: | PurposeCiliary 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.MethodsFifty-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.ResultsSeven 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.ConclusionsIntravitreal 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. |
| Databáze: | OpenAIRE |
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