Intranasal administration of erythropoietin rescues the photoreceptors in degenerative retina: a noninvasive method to deliver drugs to the eye
Intranasal administration of erythropoietin rescues the photoreceptors in degenerative retina: a noninvasive method to deliver drugs to the eye
复制标题
DOI：
10.1080/10717544.2018.1556361
复制
发表时间：
2019-01
期刊：
影响因子：
6
通讯作者：
Ye Tao;Chong Li;Anhui Yao;Yingxin Qu;Limin Qin;Zuojun Xiong;Jianbin Zhang;Weiwen Wang
中科院分区：
文献类型：
--
作者：
Ye Tao;Chong Li;Anhui Yao;Yingxin Qu;Limin Qin;Zuojun Xiong;Jianbin Zhang;Weiwen Wang
摘要遗传性视网膜病通常会导致受试者感光细胞丧失和严重的视力障碍。鼻内给药是将治疗剂递送至靶组织的有效方法。本研究旨在将促红细胞生成素（EPO）通过鼻内或静脉途径递送到N-甲基-N-亚硝基脲（MNU）诱导的药物性视网膜病变模型小鼠体内。然后对小鼠进行生物利用度测定和治疗效果评价。我们的结果表明，鼻内给药的EPO是有效的，以减轻MNU诱导的小鼠的形态学破坏。EPO的鼻内给药也改善了MNU诱导的小鼠的视觉障碍。免疫染色实验表明，鼻内递送EPO可以拯救退行性视网膜中的M-视锥和S-视锥群体。特别地，鼻内递送EPO优先保留背颞（DT）象限中的M-视锥光感受器和腹鼻（VN）象限中的S-视锥光感受器。机制研究表明，鼻内给药EPO可调节视网膜变性的细胞凋亡和抑制氧化。与静脉给药相比，鼻内给药导致视网膜中EPO浓度显著升高。鼻内递送导致更有效的保护，并且比静脉内递送具有更少的红细胞生成刺激活性。我们的研究结果表明，鼻内给药是一种非侵入性和有效的方法，将EPO输送到视网膜。这些发现奠定了基础，进一步鼻内给药的EPO在眼科的实践。
Abstract Inherited retinopathies typically lead to photoreceptor loss and severe visual impairments in the subjects. Intranasal administration is an efficient approach to deliver therapeutic agents to the targeted tissue. The present study is designed to deliver the erythropoietin (EPO) into the N-methyl-N-nitrosourea (MNU) induced mice, a pharmacological retinopathy model via intranasal or intravenous route. The mice were then subjected to bioavailability assay and therapeutic effects evaluation. Our results showed that the intranasal delivery of EPO is effective to alleviate the morphological disruptions in the MNU induced mice. The intranasal delivery of EPO also ameliorated the visual impairments in the MNU induced mice. Immunostaining experiment showed that both the M-cone and S-cone populations in the degenerative retinas are rescued by the intranasal delivery of EPO. In particular, the M-cone photoreceptors in dorsal-temporal (DT) quadrant and the S-cone photoreceptors in ventral-nasal (VN) quadrant were preferentially preserved by the intranasal delivery of EPO. Mechanism studies showed that the intranasal delivery of EPO could the modulate apoptosis and restrict oxidation in the degenerative retina. Compared with intravenous delivery, the intranasal delivery led to the significantly higher EPO concentration in the retina. The intranasal delivery resulted in more potent protection and had less erythropoiesis-stimulating activity than the intravenous delivery. Our results suggest that the intranasal administration is a noninvasive and efficient approach to deliver EPO into the retinas. These findings lay the groundwork for further intranasal administration of EPO in ophthalmological practice.