Impacts of ciliary neurotrophic factor on the retinal transcriptome in a mouse model of photoreceptor degeneration

Ciliary neurotrophic factor (CNTF) has been tested in clinical trials for human retinal degeneration due to its potent neuroprotective effects in various animal models. To decipher CNTF-triggered molecular events in the degenerating retina, high-throughput RNA sequencing analyses were performed using the Rds/Prph2 (P216L) transgenic mouse as a preclinical model for retinitis pigmentosa. Retinal transcriptome data was obtained for untreated wild type retinas, Rds retinas treated with a lentivirus expressing CNTF from postnatal day 25 to 35, and Rds retinas similarly treated with a control lentivirus expressing GFP. Comparisons of transcriptome data detect significant changes between wild type and Rds retinas. In addition, RNA-seq data reveal elevation of transcripts in the innate immune system and growth factor signaling, as well as altered neuronal transmission and metabolism in CNTF-treated Rds retinas. These results demonstrate the influence of exogenous CNTF on the retinal transcriptome landscape and illuminate likely CNTF impacts in degenerating human retinas. Overall design: Mouse retinas carried an rds mutation was treated with CNTF for 10 days by lentivirues-mediated delivery. Retinal transcriptomes of wild type and rds mutant retinas treated with lentivurs expressing CNTF or control lentivirus expressing GFP were analyzed by high throughput sequnecing.