Artikel
Physiological findings of experimental pig models with outer retinal degeneration induced by intravitreal loading of Nmethyl-N-nitrosourea after vitrectomy
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Veröffentlicht: | 10. Dezember 2019 |
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Gliederung
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Objective: Degenerated retina shows abnormal histological and physiological features compared with normal retina. Thus, understanding of retinal degeneration (RD) network through animal model is a prerequisite for the development of retinal prosthesis. Here, we report a new canine model of drug-induced RD with sodium iodate (SI) injection after vitrectomy. Materials and methods: SI (1.2 mg) was injected at 2 weeks after vitrectomy in the right eyeball of canines (n=6). For the observation of histological changes, we performed H&E staining and immunohistochemistry (IHC) after 1 (n=1), 3 (n=2) and 6 (n=2) months of injection. Also, we recorded the spiking activity of retinal ganglion cells (RGCs) in response to light (full field flash) and electrical stimulation in 4 different retinal regions [Tapetum Lucidum-Nasal (LN), Lucidum-Temporal (LT), Nigrum-Nasal (NN) and Nigrum-Temporal (NT)] with in-vitro multielectrode array (MEA) at 6 month after SI injection.
Results: In H&E and IHC study, PNA and rhodopsin signals decreased rapidly after 3 months but not disappeared completely, although PKCα, NeuN and GFAP signals rarely changed. In MEA study, we observed debatable finding in SI-injected retina: LN and NT regions showed a loss of light response. But LT and NN regions preserve light response. The electrical responses of RGCs were found in both SI-injected and normal retinal patches.
Discussion: In histology, 1.2 mg of SI induced the localized RD only in outer not in inner retina of canine model. However, in MEA recording, LN and NT regions lost light evoked response, which was opposite with the response of LT and NN regions. SI dose optimization is needed to establish solid outer RD model in dogs for a preclinical study for developing the retinal prosthesis.
Supported by ational Research Foundation (NRF) of Korea grant funded by the Korea government (NRF-2017M3A9E2056460 and NRF-2017M3A9E2056458)