Tamoxifen protects photoreceptors in the sodium iodate model

• Published in: Experimental eye research 2024-05, Vol.242, p.109879-109879, Article 109879
• Main Authors: Lee, Timothy T., Bell, Brent A., Anderson, Brandon D., Song, Ying, Dunaief, Joshua L.
• Format: Article
• Language: English
• Subjects: Animals; Disease Models, Animal; Electroretinography; Iodates - toxicity; Mice; Mice, Inbred C57BL; Photoreceptor Cells, Vertebrate - drug effects; Photoreceptor Cells, Vertebrate - pathology; Real-Time Polymerase Chain Reaction; Retinal degeneration; Retinal Degeneration - chemically induced; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Retinal Degeneration - prevention & control; Retinal Pigment Epithelium - drug effects; Retinal Pigment Epithelium - metabolism; Retinal Pigment Epithelium - pathology; Retinal protection; Rhodopsin - genetics; Rhodopsin - metabolism; RNA, Messenger - genetics; Rod Opsins - metabolism; Selective Estrogen Receptor Modulators - pharmacology; Sex; Sodium iodate; Tamoxifen; Tamoxifen - pharmacology; Tomography, Optical Coherence - methods
• ISSN: 0014-4835; 1096-0007
• DOI: 10.1016/j.exer.2024.109879

Because the selective estrogen receptor modulator tamoxifen was shown to be retina-protective in the light damage and rd10 models of retinal degeneration, the purpose of this study was to test whether tamoxifen is retina-protective in a model where retinal pigment epithelium (RPE) toxicity appears to be the primary insult: the sodium iodate (NaIO3) model. C57Bl/6J mice were given oral tamoxifen (in the diet) or the same diet lacking tamoxifen, then 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. Tamoxifen administration partially protected photoreceptors. There was less photoreceptor layer thinning in OCT images of tamoxifen-treated mice. qRT-PCR revealed, in the tamoxifen-treated group, less upregulation of antioxidant and complement factor 3 mRNAs, and less reduction in the rhodopsin and short-wave cone opsin mRNAs. Furthermore, ERG results demonstrated preservation of photoreceptor function for the tamoxifen-treated group. Cone function was better protected than rods. These results indicate that tamoxifen provided structural and functional protection to photoreceptors against NaIO3. RPE cells were not protected. These neuroprotective effects suggest that estrogen-receptor modulation may be retina-protective. The fact that cones are particularly protected is intriguing given their importance for human visual function and their survival until the late stages of retinitis pigmentosa. Further investigation of this protective pathway could lead to new photoreceptor-protective therapeutics. •Tamoxifen provides structural and functional photoreceptor protection against NaIO3.•Tamoxifen results in more functional protection for cones than rods.•Estrogen-receptor modulation may be retina-protective.