Suppressing thyroid hormone signaling preserves cone photoreceptors in mouse models of retinal degeneration

摘要: Cone phototransduction and survival of cones in the human macula is essential for color vision visual acuity. Progressive cone degeneration age-related macular degeneration, Stargardt disease, recessive dystrophies a major cause blindness. Thyroid hormone (TH) signaling, which regulates cell proliferation, differentiation, apoptosis, plays central role opsin expression patterning retina. Here, we investigated whether TH signaling affects viability inherited retinal mouse models. Retinol isomerase RPE65-deficient mice [a model Leber congenital amaurosis (LCA) with rapid loss] photoreceptor function loss type 1 (severe achromatopsia) were used to determine suppressing antithyroid treatment reduces death. Further, cyclic nucleotide-gated channel B subunit-deficient (moderate guanylate cyclase 2e-deficient (LCA slower loss) triiodothyronine (T3) (stimulating signaling) causes deterioration cones. We found that density retinol increased about sixfold following treatment. decreased 40% T3 The effect on appears be independent its regulation expression. This work demonstrates retina dystrophy models protective cones, providing insights into preservation therapeutic interventions.