title: N -methyl- N -nitrosourea-induced retinal degeneration in mice.
abstract: Mouse retinal degeneration models have been investigated for many years in the hope of understanding the mechanism of photoreceptor cell death. N -methyl- N -nitrosourea (MNU) has been previously shown to induce outer retinal degeneration in mice. After MNU was intraperitoneally injected in C57/BL mice, we observed a gradual decrease in the outer nuclear layer (ONL) thickness associated with photoreceptor outer segment loss, bipolar cell dendritic retraction and reactive gliosis. Reactive gliosis was confirmed by increased GFAP protein levels. More serious damage to the central retina as opposed to the peripheral retina was found in the MNU-induced retinal degeneration model. Retinal ganglion cells (RGC) appear to be spared for at least two months after MNU treatment. Following retinal vessel labelling, we observed vascular complexes in the distal vessels, indicating retinal vessel damage. In the remnant retinal photoreceptor of the MNU-treated mouse, concentrated colouring nuclei were detected by electron microscopy, together with the loss of mitochondria and displaced remnant synaptic ribbons in the photoreceptor. We also observed decreased mitochondrial protein levels and increased amounts of nitrosylation/nitration in the photoreceptors. The mechanism of MNU-induced apoptosis may result from oxidative stress or the loss of retinal blood supply. MNU-induced mouse retinal degeneration in the outer retina is a useful animal model for photoreceptor degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).
authors: Dept of Ophthalmology, Wuhan Univ, Renmin Hospital, Wuhan, China; Eye Institute of Wuhan University, Wuhan, China.
authors: Yuan-Yuan
authors: YY
authors: Chen
authors: Dept of Ophthalmology, Wuhan Univ, Renmin Hospital, Wuhan, China; Eye Institute of Wuhan University, Wuhan, China.
authors: Shi-Liang
authors: SL
authors: Liu
authors: Dept of Ophthalmology, Wuhan Univ, Renmin Hospital, Wuhan, China; Eye Institute of Wuhan University, Wuhan, China.
authors: Dan-Ping
authors: DP
authors: Hu
authors: Dept of Ophthalmology, Wuhan Univ, Renmin Hospital, Wuhan, China; Eye Institute of Wuhan University, Wuhan, China. Electronic address: xyqdr07@gmail.com.
authors: Yi-Qiao
authors: YQ
authors: Xing
authors: Dept of Ophthalmology, Wuhan Univ, Renmin Hospital, Wuhan, China; Eye Institute of Wuhan University, Wuhan, China. Electronic address: yinshen@whu.edu.cn.
authors: Yin
authors: Y
authors: Shen
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D007274:Injections, Intraperitoneal; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000648:ultrastructure; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000473:pathology; D055351:Retinal Neurons / Q000187:drug effects / Q000648:ultrastructure
chemical_list: D000477:Alkylating Agents; D015415:Biomarkers; D005136:Eye Proteins; D008770:Methylnitrosourea
keywords: N -methyl- N -nitrosourea; photoreceptor; remodelling; retinal degeneration; retinal vessel; ribbon synapse