Tao Ye, Chen Tao, Fang Wei, Yan Zhongjun, Yang Qinghua, Huang Yifei, Yu Linjun, Fan Lingling
Department of Ophthalmology, Ophthalmology and Visual Science Key Lab of PLA, Chinese PLA General HospitalBeijing, China.
Department of Aerospace Health Service, Fourth Military Medical UniversityXi'an, China.
Front Pharmacol. 2017 Aug 29;8:587. doi: 10.3389/fphar.2017.00587. eCollection 2017.
Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal diseases leading to blindness. The present study explored the protective effects of hydrogen rich saline (HRS) against the photoreceptor degeneration in the -Methyl--nitrosourea (MNU) administrated rat, a pharmacologically induced RP model. The therapeutic effects of intraperitoneal (IP) and intravitreous (IV) injections of HRS on regional retina was quantified via topographic measurements. The MNU administrated rats received IV or IP injections of HRS, and then they were subjected to electroretinography, multi electrode array, histological and immunohistochemistry examinations. The concentrations of the retinal malondialdehyde (MDA), superoxide dismutase (SOD), as well as the mRNA levels of apoptotic-associated genes were quantified. The IP and IV delivery pathways of HRS were both effective to ameliorate MNU induced photoreceptor degeneration. Moreover, the IV acted as a more efficient delivery method than the IP in terms of therapeutic effects. Particularly, the topographic measurements suggested that the IV delivery of HRS could alleviate MNU induced photoreceptor degeneration in the posterior retina. The immunostaining experiments also verified the comparative efficiency between IV and IP delivery of HRS on regional cone photoreceptors. Focal cone photoreceptors showed different susceptibilities to HRS and exhibited as a distinct spatial disequilibrium: cone photoreceptors in the ST quadrant were preferentially rescued; meanwhile, HRS induced protection was feeblest in the IN quadrant. Furthermore, the HRS treatment increased the level of retinal SOD, while reduce the level of retinal MDA in MNU administered rats. The expression levels of sever apoptotic -associated genes were significantly altered by HRS treatment. Collectively, these findings suggest that the IV space is an excellent target for HRS delivery. The IV delivery of HRS can efficiently alleviate the photoreceptors (especially these locate at the posterior retina) from MNU toxicity and act as a candidate treatment for RP.
视网膜色素变性(RP)是一组导致失明的遗传性视网膜疾病的异质性群体。本研究探讨了富氢盐水(HRS)对经甲基亚硝基脲(MNU)处理的大鼠(一种药理学诱导的RP模型)光感受器变性的保护作用。通过地形图测量对腹腔内(IP)和玻璃体内(IV)注射HRS对局部视网膜的治疗效果进行了量化。给经MNU处理的大鼠进行IV或IP注射HRS,然后对它们进行视网膜电图、多电极阵列、组织学和免疫组织化学检查。对视网膜丙二醛(MDA)、超氧化物歧化酶(SOD)的浓度以及凋亡相关基因的mRNA水平进行了量化。HRS的IP和IV给药途径均能有效改善MNU诱导的光感受器变性。此外,就治疗效果而言,IV作为一种给药方法比IP更有效。特别是,地形图测量表明,IV注射HRS可减轻MNU诱导的后极部视网膜光感受器变性。免疫染色实验也证实了HRS的IV和IP给药在局部视锥光感受器上的相对效率。局灶性视锥光感受器对HRS表现出不同的敏感性,并呈现出明显的空间失衡:ST象限的视锥光感受器优先得到挽救;与此同时,HRS诱导的保护在IN象限最弱。此外,HRS治疗可提高经MNU处理的大鼠视网膜SOD水平,同时降低视网膜MDA水平。HRS治疗显著改变了多个凋亡相关基因的表达水平。总体而言,这些发现表明IV腔隙是HRS给药的理想靶点。IV注射HRS可有效减轻光感受器(尤其是位于后极部视网膜的光感受器)免受MNU毒性的影响,并可作为RP的一种候选治疗方法。