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Abstract:
PURPOSE. To clone, map, and determine the site of expression (mRNA and protein) of the a subunit of the receptor for ciliary neurotrophic factor (CNTFRalpha) in the normal adult canine retina.METHODS. The complete coding sequence of the canine CNTFRa cDNA was cloned, and radiation hybrid (RH) mapping was used to determine the chromosomal localization of the gene. CNTFRa mRNA expression in retina and other tissues was examined by reverse transcription-polynterase chain reaction. The cellular distribution of CNTFRa in the canine retina was studied by in situ hybridization and immunocytochemistry.RESULTS. Canine CNTFRa shares a high degree of homology with the human, mouse, and rat coding sequences, both at the nucleotide and amino acid level, but has lower homology with the chicken. CNTFRa was RH mapped to CFA 11 (Canis familiaris autosome 11) in the dog, a region showing homology to the short arm of human chromosome 9 (9P13). The gene is transcribed in retina, brain, spleen, lung, liver, and kidney. In the retina, CNTFRa was highly expressed by photoreceptors, but both the transcript and protein were also found in the RPE, inner nuclear layer, and ganglion cells.CONCLUSIONS. These findings demonstrate that CNTFRa is expressed by rods and cones in the normal adult canine retina and suggest that ciliary neurotrophic factor (CNTF) could have a direct photoreceptor rescue effect by binding to CNTFRa in these cells. This could open novel pathways for the treatment of retinal degeneration in animal models and humans.
