Testosterone promotes photoreceptor degeneration in the sodium iodate model

Previously, we found that retinas of young male mice were more damaged than those of young female mice in the sodium iodate (NaIO3) model. The purpose of this study was to test whether reducing testosterone levels would be retina-protective. Male C57Bl/6J mice underwent surgical castration or sham surgery, then were given an intraperitoneal injection of NaIO3 at 25 mg/kg. The mice were imaged a week later using optical coherence tomography (OCT). ImageJ with a custom macro was utilized to measure retinal thicknesses in OCT images. Electroretinography (ERG) was used to measure retinal function one week post-injection. After euthanasia, quantitative real-time PCR (qRT-PCR) was performed. Surgical castration partially protected photoreceptors, which was indicated by less photoreceptor layer thinning exhibited in OCT images compared to the sham surgery group. Consistent with this, qRT-PCR of castration group neural retinas revealed less reduction of rhodopsin mRNAs, and less upregulation of antioxidant as well as glucose transporter 1 mRNAs. ERG results also demonstrated partial preservation of both cone and rod function. These results indicate that surgical castration provided structural and functional protection to photoreceptors against NaIO3. These neuroprotective effects suggest that testosterone may be harmful to the stressed retina. Further investigation of this pathway could lead to a better understanding of the mechanisms involved in retinal degeneration. •Testosterone promotes structural and functional photoreceptor degeneration in NaIO3.•Testosterone promotes NaIO3 oxidative stress in the neural retina.•Ovariectomy does not affect photoreceptor degeneration in NaIO3.