Retinal Gene and Protein Expression Associated with CNTF-Induced Deconstruction of Photoreceptor Outer Segments in normal and CNGB3-achromatopsia dogs

Background: Intravitreal injection of CNTF leads to deconstruction and regeneration of photoreceptor outer segments in normal dogs, and improves the success rate of viral CNGB3 gene replacement therapy in dogs (> 1 year) with CNGB3-achromatopsia. Objectives: The goal of this study was to examine the changes caused by intravitreal CNTF injection to the retinal gene expression profiles and the retinal function of normal and CNGB3-achromatopsia affected dogs. Retinal gene expression profiles were evaluated with canine specific Agilent Oligo Microarray containing 42,034 60-mer oligonucleotide probes. Expression of eleven selected genes (BCL2, CCL2, STAT3, TNFRSF1A, ARR3, RHO, TYROBP, COL1A1, C3, CNGA1, and CNGB3) was quantified in the same RNA samples by quantitative real-time PCR. The results confirmed the differential expression levels observed with the microarray analysis. Five CNGB3-mutant dogs (age: ca. 11 months; carrying the D262N missense mutation CNGB3m/m) and 5 control dogs (age: ca. 11 months; homozygous CNGB3+/+; heterozygous CNGB3+/m) were injected with either 12 µg of intravitreal CNTF (right eye: OD) or PBS (left eye: OS, used as control).