Activation of TH pathways under light adaptation regulates retinal mitochondrial respiration and cone photoresponse. (A and B) Seahorse analysis of the oxygen consumption rate (OCR) of the mouse retinae treated with 100 nmol/L T3 incubation ex vivo. OCR was measured as baseline measurements and in the presence of the indicated drugs, i.e., 20 μmol/L oligomycin, 1 μmol/L FCCP, and 1 μmol/L rotenone with 1 μmol/L antimycin A (R + A). Data are representative of three independent experiments. n = 11, ^**P < 0.01. (C) Schematic of the ex vivo ERG for T3-incubated mouse retinae. Gnat1^−/− mice lacked transducin α protein, resulting in rods that were not photosensitive and cones that were normally photosensitive. (D) Representative flash response images of a-wave under 1.13 × 10⁴ photons•μm⁻² light. The T3 incubation group showed a higher photocurrent than the control group. (E) Quantification of ERG a-wave amplitudes of light intensity-response curves from cones in normal incubation and T3 incubation. The light intensity ranged from 80.71 to 7.89 × 10⁵ photons/μm². Intensity-response data are mean ± s.e.m. intensity-response curves. n = 18, ^****P < 0.0001, Two-way ANOVA.(F) Schematic diagram of the ERG recording experiment in AAV-GFAP-Cre/GFP virus-injected Dio2^f/f mice under light adaptation. The control group was injected with AAV-GFAP-GFP, and the experimental group was injected with AAV-GFAP-Cre-GFP. ERG recordings were performed 3 weeks after the virus injection. (G) Representative flash response images of in vivo ERG b-wave under different light intensities. Light with a 495 nm wavelength was used as the stimulus light, a 20 ms flash stimulus was given, and the light intensities were 6.8 × 10⁴, 3.4 × 10⁵, 1.2 × 10⁶, 2.9 × 10⁶, and 9.8 × 10⁶ photons/μm². (H) Quantification of ERG b-wave amplitudes of light intensity-response curves with light intensities from 2.0 × 10⁴ to 9.8 × 10⁶ photons/μm². Intensity-response data were shown as the mean ± s.e.m. intensity-response curves. n = 9, ^***P < 0.001, Two-way ANOVA. (I) Summary showing that the thyroid hormone signaling pathway activated by Dio2 under light adaptation affects overall retinal mitochondrial respiration and light response.