May 2005
Volume 46, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2005
Evaluation of CNTF’s Photoreceptor Rescue Effect in Affected XLPRA2 Dogs
Author Affiliations & Notes
  • W.A. Beltran
    James A Baker Inst Animal Hlth, Cornell University, Ithaca, NY
    School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • G.M. Acland
    James A Baker Inst Animal Hlth, Cornell University, Ithaca, NY
    School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • G.D. Aguirre
    School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA
  • Footnotes
    Commercial Relationships  W.A. Beltran, None; G.M. Acland, None; G.D. Aguirre, None.
  • Footnotes
    Support  EY13132, EY06855, EY13729, FFB, SquareD/Schneider Electric Van Sloun Fund, Cornell GRA program
Investigative Ophthalmology & Visual Science May 2005, Vol.46, 169. doi:
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      W.A. Beltran, G.M. Acland, G.D. Aguirre; Evaluation of CNTF’s Photoreceptor Rescue Effect in Affected XLPRA2 Dogs . Invest. Ophthalmol. Vis. Sci. 2005;46(13):169.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Abstract: : Purpose: Previous work conducted in our lab has shown that ciliary neurotrophic factor (CNTF) protects photoreceptor cells in the rcd1 dog, a canine model of retinal degeneration caused by a mutation in PDE6B. Here, we evaluate whether CNTF provides morphologic rescue of photoreceptors in the XLPRA2 dog: a model of early onset X–linked retinitis pigmentosa caused by a mutation in exon ORF15 of RPGR. Methods: Eight XLPRA2 affected dogs were used for this study. At 4 weeks of age, all dogs received under general anesthesia an intravitreal injection of 12 µg of CNTF (30 µl of a 0.4 µg/µl solution) in the left eye (OS). The right eye (OD) served as a control and was injected intravitreally with 30 µl of PBS. All animals underwent an ocular examination at least once a week. At 8 weeks of age, 4 dogs (group 1) were euthanized and eyes enucleated. The remaining 4 dogs (group 2) received a second intravitreal injection of 12 µg of CNTF (OS), and PBS (OD). At 12 weeks of age these dogs were euthanized and their eyes were collected. Following enucleation, the eyes from 1 dog (in each of the 2 groups) were processed for Epon embedding), while the eyes from the 3 other dogs (of each group) were processed for OCT embedding. All anterior segments were postfixed in Bouin’s solution and paraffin embedded. Sections were stained with Azure II/methylene blue and PPDA counterstain (Epon sections), or H&E stain (cryo and paraffin sections) Photoreceptor rescue was assessed in all four quadrants by measuring the mean number of rows of nuclei in the ONL in 3 distinct locations (per quadrant) in the left eyes (CNTF injected) and comparing those values to that measured in the contra–lateral eye (PBS injected). Results: All eyes that received the CNTF injection(s) showed early clinical signs of corneal epitheliopathy, subcapsular cataracts and uveitis. Preliminary results from group 2 show that the ONL in the CNTF injected eyes had approximately one extra row of nuclei than the ONL of the PBS injected eyes. In addition, the ONL thickness in the CNTF injected eyes was (at 12 weeks) significantly reduced in comparison to that of 4 week–old XLPRA2 dogs. Conclusions: Intravitreal injections of CNTF may provide a mild photoreceptor rescue effect in the XLPRA2 dog, yet do not appear to arrest the course of photoreceptor cell death.

Keywords: neuroprotection • photoreceptors • retinal degenerations: hereditary 
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