Adeno-associated virus-mediated neuroglobin overexpression ameliorates the N-methyl-N-nitrosourea-induced retinal impairments: a novel therapeutic strategy against photoreceptor degeneration

In: info:eu-repo/semantics/altIdentifier/doi/10.2147/TCRM.S144822

Abstract

Ye Tao,1,* Zhen Yang,2,* Wei Fang,2 Zhao Ma,3 Yi Fei Huang,1 Zhengwei Li4 1Department of Ophthalmology, Key Lab of Ophthalmology and Visual Science, Chinese PLA General Hospital, Beijing, 2Department of Neurosurgery, Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an, 3Department of Neurosurgery, Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 4Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China *These authors contributed equally to this work Abstract: Retinal degeneration (RD) is a heterogeneous group of inherited dystrophies leading to blindness. The N-methyl-N-nitrosourea (MNU)-administered mouse is used as a pharmacologically induced RD animal model in various therapeutic investigations. The present study found the retinal neuroglobin (NGB) expression in the MNU-administered mice was significantly lower than in normal controls, suggesting NGB was correlated with RD. Subsequently, an adeno-associated virus (AAV)-2-mCMV-NGB vector was delivered into the subretinal space of the MNU-administered mice. The retinal NGB expression of the treated eye was upregulated significantly in both protein and mRNA levels. Further, we found NGB overexpression could alleviate visual impairments and morphological devastations in MNU-administered mice. NGB overexpression could rectify apoptotic abnormalities and ameliorate oxidative stress in MNU-administered mice, thereby promoting photoreceptor survival. The cone photoreceptors in MNU-administered mice were also sensitive to AAV-mediated NGB overexpression. Taken together, our findings suggest that manipulating NGB bioactivity via gene therapy may represent a novel therapeutic strategy against RD. Future elucidation of the exact role of NGB would advance our knowledge about the pathological mechanisms underlying RD. Keywords: neuroglobin, retinal degeneration, photoreceptor