Qiu Suo, Wei Yantao, Zhou Xuezhi, Jiang Zhaoxin, Zhang Ting, Jiang Xintong, Zhang Shaochong
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
Neurosci Lett. 2017 Sep 14;657:53-61. doi: 10.1016/j.neulet.2017.07.041. Epub 2017 Jul 25.
In most studies, the major supplement docosahexaenoic acid (DHA) is administered orally or intraperitoneally. In this study, we proposed to assess the safety and efficacy of the intravitreal injection of DHA in an age-related macular degeneration (AMD) rat model. Different concentrations of DHA were injected into the vitreous body. Histopathology and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) analysis showed that there was no difference in thickness, observable structure, or apoptosis among the untreated, normal saline, and DHA groups (0.2, 1.0, 5.0 and 10μg). However, GFAP expression was increased in the 10μg group. To investigate whether intravitreal injection of DHA could protect photoreceptors, we developed a NaIO-induced retinal damage model in adult rats. Decreases in deformation and thickness were observed in the outer nuclear layer (ONL) after NaIO administration but were improved with DHA injection. The NaIO group showed a substantial reduction in the number of nuclei in ONL, whereas the DHA group showed an increase. Additionally, significant increases in SOD activity and Nrf2 expression were observed after DHA injection; GFAP and NF-κB expression levels were markedly decreased by DHA injection. Moreover, Western blotting showed that Bax, cleaved caspase-3 and CHOP were notably increased in the NaIO group but were significantly decreased by DHA injection. Collectively, intravitreal injection of DHA is safe and effective in select doses in a NaIO-induced AMD rat model. The current results suggest that intravitreal injection of DHA may be a new avenue for the treatment of AMD.
在大多数研究中，主要补充剂二十二碳六烯酸（DHA）通过口服或腹腔注射给药。在本研究中，我们提议评估玻璃体内注射DHA在年龄相关性黄斑变性（AMD）大鼠模型中的安全性和有效性。将不同浓度的DHA注入玻璃体。组织病理学和末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）分析表明，未治疗组、生理盐水组和DHA组（0.2、1.0、5.0和10μg）在厚度、可观察结构或细胞凋亡方面没有差异。然而，10μg组的胶质纤维酸性蛋白（GFAP）表达增加。为了研究玻璃体内注射DHA是否能保护光感受器，我们在成年大鼠中建立了碘酸钠诱导的视网膜损伤模型。碘酸钠给药后，外核层（ONL）的变形和厚度减小，但DHA注射后有所改善。碘酸钠组ONL中的细胞核数量大幅减少，而DHA组则增加。此外，DHA注射后超氧化物歧化酶（SOD）活性和核因子E2相关因子2（Nrf2）表达显著增加；DHA注射使GFAP和核因子κB（NF-κB）表达水平明显降低。此外，蛋白质免疫印迹法显示，碘酸钠组中促凋亡蛋白Bax、裂解的半胱天冬酶-3和C/EBP同源蛋白（CHOP）显著增加，但DHA注射后显著降低。总体而言，在碘酸钠诱导的AMD大鼠模型中，玻璃体内注射特定剂量的DHA是安全有效的。目前的结果表明，玻璃体内注射DHA可能是治疗AMD的一条新途径。
