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Sun-Sook Paik, Ji Hyun Jeon, In-Beom Kim; NecroX-5 Rescue Retinal Degeneration Induced by N-methyl-N-nitrosourea in Rats. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4202. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
NecroX-5 is an indole-derived small molecule which showed anti-oxidative and anti-nitrosative effects in H9C2 cardiomyoblast and protective effect against in vivo ischemia-reperfusion injury. In this study, we examined the effect of NecroX-5 in an animal model for retinal degeneration (RD), which is one of the leading causes of photoreceptor cell death.
Retinal degeneration was induced in Sprague-Dawley rats by an intraperitoneal injection of N-methyl-N-nitrosourea (MNU) (75 mg/Kg), a DNA methylating agent, which causes selective retinal pigment epithelium damage with secondary photoreceptor cell death. NecroX-5 (50 μM) was injected intravitreally at 3 h after MNU injection. Electroretinogram (ERG) recordings and morphological analyses were performed at 1 week after MNU injection.
Marked loss of photoreceptors in the outer nuclear layer (ONL) was observed in untreated RD rats at 1 week after MNU injection, while the ONL in the MNU-induced RD rats injected with NecroX-5 was relatively well preserved. Immunohistochemistry with anti-glial fibrillary acidic protein (GFAP) showed that GFAP immunoreactivity was decreased in the retinas of the rats injected with NecroX-5, compared to that in the untreated RD rat retinas. In addition, functional assessment by using ERG recordings showed that ERG responses were significantly increased in RD rats with Necro-5 intravitreal injection (p < 0.05) compared with those of untreated RD rats.
These results demonstrate that NecroX-5 may protect retinal neurons from MNU-induced damages both structurally and functionally, suggesting that NecroX-5 has therapeutic potential for RD.
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