Lee Timothy T, Bell Brent A, Song Ying, Dunaief Joshua L
FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
Exp Eye Res. 2025 Feb;251:110221. doi: 10.1016/j.exer.2024.110221. Epub 2024 Dec 20.
Previously, we found that retinas of young male mice were more damaged than those of young female mice in the sodium iodate (NaIO) 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 NaIO 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 NaIO. 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.
此前，我们发现在碘酸钠（NaIO）模型中，年轻雄性小鼠的视网膜比年轻雌性小鼠的视网膜受损更严重。本研究的目的是测试降低睾酮水平是否具有视网膜保护作用。雄性C57Bl/6J小鼠接受手术去势或假手术，然后腹腔注射25 mg/kg的NaIO。一周后，使用光学相干断层扫描（OCT）对小鼠进行成像。利用带有自定义宏的ImageJ测量OCT图像中的视网膜厚度。在注射后一周，使用视网膜电图（ERG）测量视网膜功能。安乐死后，进行定量实时PCR（qRT-PCR）。手术去势对光感受器有部分保护作用，这表现为与假手术组相比，OCT图像中光感受器层变薄程度较轻。与此一致的是，去势组神经视网膜的qRT-PCR显示视紫红质mRNA减少较少，抗氧化剂以及葡萄糖转运蛋白1 mRNA的上调也较少。ERG结果也表明视锥和视杆功能均有部分保留。这些结果表明，手术去势为光感受器提供了针对NaIO的结构和功能保护。这些神经保护作用表明睾酮可能对处于应激状态的视网膜有害。对该途径的进一步研究可能有助于更好地理解视网膜变性所涉及的机制。
