Journal article
Establishment of Retinal Degeneration Model in Rat and Monkey by Intravitreal Injection of Sodium Iodate
Current molecular medicine, v 18(6), pp 352-364
01 Jan 2018
PMID: 30421676
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Animal models play critical roles in studies of the etiology and therapy of retinal degeneration (RD).
Objective: To establish an RD model without severe systemic side effects in monkeys.
Methods: Cynomolgus monkeys and Sprague-Dawley rats were treated with intravenous and intravitreal sodium iodate (SI). Electroretinographic (ERG) recording, fluorescein fundus angiography (FFA), optical coherence tomography (OCT) and a retinal morphology examination were conducted to evaluate retinal function and structure. ARPE-19 cells were treated with SI to assess cell viability and morphology. Glutathione (GSH) was administered to SI-treated cultured cells and rats for mechanistic studies.
Results: Intravenous SI failed to induce RD in monkeys due to its lethal toxicity and the spontaneous recovery of visual function. However, intravitreal SI injection induced very rapid and severe retinal damage in both monkeys and rats. Different doses of SI were tested in both rats and monkeys, and the SI dose appropriate for the model was calculated. GSH partially rescued oxidative damage to SI-treated retinas. A combination of the appropriate dose of intravitreal SI and intravenous GSH generated moderate subacute RD.
Conclusions: An RD model was established in cynomolgus monkeys by intravitreal SI injection. The key advantages of this model are that lethal SI side effects can be avoided and that the structural and functional changes are similar to those in patients with RD, although the development of RD in the model is too rapid and more severe. An appropriate dose of SI plus systemic GSH generates delayed and moderate RD; this prolonged therapeutic window allows the development of new therapies, such as gene or stem cell-based therapy, for RD.
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Details
- Title
- Establishment of Retinal Degeneration Model in Rat and Monkey by Intravitreal Injection of Sodium Iodate
- Creators
- Qingjian Ou - Shanghai Tenth People's HospitalTong Zhu - Shanghai Tenth People's HospitalPeng Li - Shanghai Tenth People's HospitalZongyi Li - Shanghai Tenth People's HospitalLi Wang - Shanghai Tenth People's HospitalChunpin Lian - Shanghai Tenth People's HospitalHua Xu - Shanghai Tenth People's HospitalCaixia Jin - Shanghai Tenth People's HospitalFurong Gao - Shanghai Tenth People's HospitalJing-Ying Xu - Shanghai Tenth People's HospitalJuan Wang - Shanghai Tenth People's HospitalJieping Zhang - Shanghai Tenth People's HospitalWeiye Li - Drexel UniversityHaibin Tian - Shanghai Tenth People's HospitalLixia Lu - Shanghai Tenth People's HospitalGuo-Tong Xu - Shanghai Tenth People's Hospital
- Publication Details
- Current molecular medicine, v 18(6), pp 352-364
- Publisher
- Bentham Science Publ Ltd
- Number of pages
- 13
- Grant note
- 2015CB964601; 2017YFA0104100; 2016YFA0101302 / Ministry of Science and Technology of China; Ministry of Science and Technology, China 201640229 / Shanghai Municipal Commission of Health and Family Planning project ZJ2014-ZD-002 / Shanghai East Hospital 17ZR1431300 / Shanghai Science and Technology Committee Grant 81670867; 81370999; 81372071; 81770942; 81500733 / National Natural Science Foundation; National Natural Science Foundation of China (NSFC)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Ophthalmology [Historical]
- Web of Science ID
- WOS:000456940200002
- Scopus ID
- 2-s2.0-85061500865
- Other Identifier
- 991019167533504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Medicine, Research & Experimental