Ophthalmology Department of Affiliated Hospital of North Sichuan Medical College, Medical School of Ophthalmology & Optometry, Nanchong, Sichuan Province, 637000, China.
Medical School of Ophthalmology & Optometry, North Sichuan Medical College, Nanchong, Sichuan Province, 637000, China.
BMC Ophthalmol. 2024 Nov 14;24(1):497. doi: 10.1186/s12886-024-03754-6.
In recent years, the global prevalence of myopia has reached an unprecedented level, especially in East Asia. Multitude of studies has shown that the etiology of myopia is complex. Some researchers have suggested that oxidative stress (OS) may contribute to myopia, although there are limited reports on the alterations of related signaling pathways. Notably, the Kelch-like ECH-associated protein 1 (KEAP1) -nuclear factor erythroid 2-related factor 2 (NRF2), which plays a significant role in regulating OS and the mechanism, has not been explored in myopia. To investigate the modulation of KEAP1-NRF2 signaling pathway and its downstream superoxide dismutase (SOD) during the development of form-deprivation myopia, three-week-old guinea pigs were randomly assigned to four groups: negative control (NC), self-control (SC), form-deprivation myopia (FDM), and FDM group treated with tert-butylhydroquinone (TBHQ). Spherical equivalent (SE) and axial length (AL) were measured by retinoscopy and A-scan ultrasound, respectively. The results revealed that TBHQ treatment decelerated the progression in SE and AL changes. Immunohistochemistry (IHC) assessed the distribution and expression of KEAP1, NRF2, and SOD. The results shown that they located in the retinal ganglion cells (RGC). Subsequently, retinal mRNA and protein expression levels of KEAP1, NRF2, and SOD were quantified using real-time polymerase chain reaction (RT-PCR) and Western blot (WB) analysis. The RT-PCR and WB results demonstrated that TBHQ could activate NRF2, induce KEAP1 degradation, and enhance the expression of the antioxidant SOD. In summary, the modulation of KEAP1-NRF2 and it downstream SOD expression could alter the retinal antioxidant capacity and influence the development of myopia.
近年来，近视的全球患病率达到了前所未有的水平，尤其是在东亚地区。大量研究表明，近视的病因复杂。一些研究人员认为氧化应激（OS）可能导致近视，尽管有关相关信号通路改变的报道有限。值得注意的是，Kelch-like ECH-associated protein 1（KEAP1）-nuclear factor erythroid 2-related factor 2（NRF2）在调节 OS 和机制方面起着重要作用，在近视中尚未得到探索。为了研究在形觉剥夺性近视发展过程中 KEAP1-NRF2 信号通路及其下游超氧化物歧化酶（SOD）的调节作用，将 3 周龄豚鼠随机分为 4 组：阴性对照组（NC）、自身对照组（SC）、形觉剥夺性近视组（FDM）和 FDM 组用叔丁基对苯二酚（TBHQ）处理。通过视网膜检影法和 A 型超声分别测量球镜等效（SE）和眼轴（AL）。结果表明，TBHQ 处理可减缓 SE 和 AL 变化的进展。免疫组织化学（IHC）评估了 KEAP1、NRF2 和 SOD 的分布和表达。结果表明，它们位于视网膜神经节细胞（RGC）中。随后，使用实时聚合酶链反应（RT-PCR）和 Western blot（WB）分析定量测定视网膜 KEAP1、NRF2 和 SOD 的 mRNA 和蛋白表达水平。RT-PCR 和 WB 结果表明，TBHQ 可以激活 NRF2，诱导 KEAP1 降解，并增强抗氧化剂 SOD 的表达。总之，KEAP1-NRF2 及其下游 SOD 表达的调节可以改变视网膜的抗氧化能力并影响近视的发展。
