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Onkar Sawant, Banumathi Tamilselvan, Amanda Horton, Ivy S Samuels, Sujata Rao; Role of Type II deiodinase (Dio2) and circadian clock gene Bmal1 in photoreceptor development. Invest. Ophthalmol. Vis. Sci. 2016;57(12):563.
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© ARVO (1962-2015); The Authors (2016-present)
Recent findings from our group demonstrated that light exposure during early postnatal period is crucial for rod photoreceptor development and maturation. We also reported that these light dependent developmental processes in the eye are mediated by alterations in thyroid hormones (TH). The purpose of this study was to investigate if retinal components of TH signaling are under circadian control and to determine the role of thyroid activating enzyme Dio2 and circadian clock gene Bmal1 in cone development.
Mouse pups were reared under cyclic light-dark conditions (LD) or in constant darkness (DD) from post natal day 1 (P1) to post natal day P24 (P24). Retinal expression of thyroid activating enzyme type II deiodinase (Dio2), thyroid deactivating enzyme type III deiodinase (Dio3) and thyroid hormone receptor (Trβ2) was assessed in DD and LD animals using RT-PCR and western blot. Dio2 null mice were used to assess role of Dio2 in photoreceptor development. Photoreceptor specific Cre line (CrxCre/+) was used to achieve conditional deletion of Bmal1 from developing photoreceptors. Retinas from Dio2 and Bmal1 mutant mice were collected at P10, P17 and P24 to determine expression and distribution of rhodopsin, S-opsin and M-opsin using immunohistochemistry and whole mount immunofluorescence. Quantification of cone density and opsin distribution was performed using ImageJ. Immunofluorescence data was confirmed by RT-PCR and western blot. Dark and light-adapted ERGs were performed at P24 to assay for visual function.
We observed a significant reduction in retinal Dio2 expression in the DD group compared to the LD group at all ages. Both Dio2 and Bmal1 mutant animals have disrupted gradient of cone opsins. ERG data at P24 revealed reduced b-wave responses under light and dark adapted conditions in conditional Bmal1 mutant animals compared to controls. Dark-adapted a-wave amplitudes were comparable between conditional Bmal1 mutants and controls.
Our data demonstrates that thyroid activating enzyme Dio2 may be under circadian control and Dio2 and circadian clock gene Bmal1 are required for photoreceptor development.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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