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SAFETY OF INTRAVITREALLY ADMINISTERED RECOMBINANT ERYTHROPOIETIN (AN AOS THESIS)

机译:内输卵管重组红蛋白的安全性(AOS论文)

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Purpose: This study investigated the safety and potential retinal toxicity of intravitreally administered erythropoietin (EPO) in a rodent animal model. Methods: Forty-two healthy Sprague-Dawley rats were divided into one of 7 groups (N = 6 per group): control, sham injection, vehicle injection, and EPO injections of 50 ng (5 U), 100 ng (10 U), 250 ng (25 U), and 625 ng (62.5 U). Only the right eye was treated in each animal. Standard full-field dark- and light-adapted electroretinography (ERG) was obtained at 1 day prior to injection and then on postinjection days 3, 7, 14, and 21. Intraocular pressure (IOP) was measured at the conclusion of each ERG recording. Animals were sacrificed and the eyes underwent histologic examination with light microscopy and hematoxylin-eosin staining. Results: Rod peak, scotopic, and photopic responses (amplitude and latency) were not statistically different in the animals receiving 50 to 100 ng EPO. In the 250-ng group, the photopic b-wave amplitude at day 21 was elevated (P <.05), whereas in the 625-ng group, the scotopic OP3 latency ratio was higher at baseline (P <.05). No significant histologic abnormalities were noted except for one animal (625-ng group) with qualitative differences in retinal layer thickness and cellular density. Conclusions: Intravitreal administration of EPO (at doses up to 625 ng) does not cause adverse effects on retinal function as assessed by ERG. Moreover, single intravitreal dosing does not appear to elicit retinal neovascularization. Further investigation is warranted to assess fully the potential of this neuroprotective cytokine as a treatment for glaucoma.
机译:目的:本研究调查了在啮齿动物模型中玻璃体内施用促红细胞生成素(EPO)的安全性和潜在的视网膜毒性。方法:将42只健康Sprague-Dawley大鼠分为7组(每组N = 6)之一:对照组,假注射,媒介物注射和EPO注射50 ng(5 U),100 ng(10 U) ,250 ng(25 U)和625 ng(62.5 U)。在每只动物中仅右眼被治疗。在注射前1天,然后在注射后第3、7、14和21天,获得标准的全场暗和光适应性视网膜电图(ERG)。在每次ERG记录结束时测量眼内压(IOP)。 。处死动物,并用光学显微镜和苏木精-伊红染色对眼睛进行组织学检查。结果:在接受50至100 ng EPO的动物中,杆峰,暗视和视光反应(幅度和潜伏期)无统计学差异。在250 ng组中,第21天的明视b波振幅升高(P <.05),而在625 ng组中,暗视OP3潜伏期比率在基线时更高(P <.05)。除了一只动物(625 ng组)的视网膜层厚度和细胞密度有质的差异外,没有发现明显的组织学异常。结论:ERG评估玻璃体内给予EPO(最大剂量625 ng)不会对视网膜功能产生不利影响。而且,单次玻璃体内给药似乎未引起视网膜新血管形成。有必要进行进一步的研究,以充分评估这种神经保护性细胞因子作为治疗青光眼的潜力。

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