A combination treatment based on drug repurposing demonstrates mutation agnostic efficacy in pre-clinical retinopathy models. [RNA-seq: Rd10]
To determine the gene expression changes in the retina of two separate groups (experimental groups: vehicle and TMB) of vivarium-reared 5-week-old Rd10 mice (strong disease), as well as one group of 4-week-old dark-reared Rd10 mice (mild disease) and one group of wild-type mice (healthy). TMB group received dietary administration of tamsulosin, metoprolol and bromocriptine drug cocktail between 4-5-weeks of age, for 9 days prior to sample collection. All other groups received base/vehicle diet. Overall design: Experimental Rd10 mice were dark reared between P0-P28. Dietary tamsulosin, metoprolol and bromocriptine (TMB) administration was started at P28. Another group remained on a base/vehicle diet. One day later at P29, the vehicle- and TBM-treated Rd10 mice were transferred to normal vivarium conditions which induced faster progressing retinal degeneration. At P37, the mice were euthanized under ketamine & xylazine anesthesia, and the eyes were enucleated, retinas dissected, and RNA was extracted from the one retina per mouse. One group of C57BL/6J mice (healthy control) experienced the same housing conditions and were euthanized for sample collection at P37 under ketamine & xylazine anesthesia. One group of Rd10 mice was reared under darkness throughout their life and euthanized without experience to light at P28 under ketamine & xylazine anesthesia. The dark reared Rd10 mice carry the disease, but the phenotype is milder due to protective effect of dark rearing in this retinal degeneration model.