Objective To explore the characteristics of N-Nitroso-N-methylurea （MNU） induced retinal degeneration in mice. Methods Experimental study. Thirty-two C57/BL mice （5 weeks） in total were randomly divided into two groups： a control group and a MNU group. Sixty mg·kg-1 of MNU was intraperitonealy injected in mice， leading to damage of retinal photoreceptors， while the control group was given physiological saline. The eyes of each group were enucleated at 3 d， 7 d and 14 d after injection. The slides were stained by immunofluorescence labeling to observe the morphological changes to the photoreceptors in MNU-induced retinal damage. Retinal flat-mount immunofluorescence was performed to observe the change in ganglion cells. The ultrastructures of the nucleus， mitochondria and synaptic ribbon were observed under transmission electron microscope. Ganzfeld electroretinogram ERG was used to test the electrophysiological changes. The data were analyzed using independent t test. Results After MNU administration， immunofluorescence labeling showed a gradual decrease in the thickness of the outer nuclear layer （ONL）， the loss of photoreceptors labeled with anti-OPN1SW， reactive gliosis with anti-glial fibrillary acidic protein （GFAP） and oxidative damage in photoreceptors labeled with anti-nitrosylation. Brn-3a labeled ganglion cells did not appear to be lost two weeks after MNU administration. Electron microscopy showed concentrated coloring of the nucleus in the photoreceptor nucleus and the disappearance of mitochondria and metabolic synaptic ribbons after MNU administration. ERGs revealed that mice with MNU treatment showed a-waves and b-waves with reduced amplitudes. Conclusion MNU induced retinal apoptosis of ONL and outer piexiform layer. MNU administrated mice show similar electrophysiological results to retintis pigmentosa.
Nambu H， Yuge K， Nakajima M， et al. Morphologic characteristics of N-methyl-N-nitrosourea-induced retinal degeneration in C57BL mice[J]. Pathol Int，1997，47（6）：377-383.
[2]
Marmor MF， Fulton AB， Holder GE， et al. ISCEV Standard for full-field clinical electroretinography （2008 update）[J]. Doc Ophthalmol，2009，118（1）：69-77.
[3]
Sterling P， Matthews G. Structure and function of ribbon synapses[J]. Trends Neurosci，2005，28（1）：20-29.
[4]
Taomoto M， Nambu H， Senzaki H， et al. Retinal degeneration induced by N-methyl-N-nitrosourea in Syrian golden hamsters[J]. Graefes Arch Clin Exp Ophthalmol，1998，236（9）：688-695.
[5]
McCall MA， Gregg RG， Merriman K， et al. Morphological and physiological consequences of the selective elimination of rod photoreceptors in transgenic mice[J]. Exp Eye Res，1996，63（1）：35-50.
[6]
Hong DH， Pawlyk BS， Shang J， et al. A retinitis pigmentosa GTPase regulator （RPGR）-deficient mouse model for X-linked retinitis pigmentosa （RP3）[J]. Proc Natl Acad Sci USA，2000， 97（7）：3649-3654.
[7]
Yoshizawa K， Tsubura A. Characteristics of N-methyl-N-nitrosourea-induced retinal degeneration in animals and application for the therapy of human retinitis pigmentosa[J]. Nihon Ganka Gakkai Zasshi，2005，109（6）：327-337.
[8]
Nagar S， Krishnamoorthy V， Cherukuri P， et al. Early remodeling in an inducible animal model of retinal degeneration[J]. Neuroscience，2009，160（2）：517-529.
[9]
Adamus G， Wang S， Kyger M， et al. Systemic immunotherapy delays photoreceptor cell loss and prevents vascular pathology in Royal College of Surgeons rats[J]. Mol Vis，2012，18（9）：2323-2337.
[10]
Villegas-Perez MP， Lawrence JM， Vidal-Sanz M， et al. Ganglion cell loss in RCS rat retina： a result of compression of axons by contracting intraretinal vessels linked to the pigment epithelium[J]. J Comp Neurol，1998，392（1）：58-77.
[11]
Yuge K， Nambu H， Senzaki H， et al. N-methyl-N-nitrosourea-induced photoreceptor apoptosis in the mouse retina[J]. In Vivo， 1996，10（5）：483-488.
[12]
Chinta SJ， Andersen JK. Nitrosylation and nitration of mitochondrial complex I in Parkinson′s disease[J]. Free Radic Res，2011，45（1）：53-58.
[13]
Yoshizawa K， Yang J， Senzaki H， et al. Caspase-3 inhibitor rescues N-methyl-N-nitrosourea-induced retinal degeneration in Sprague-Dawley rats[J]. Exp Eye Res，2000，71（6）：629-635.
[14]
Uehara N， Miki K， Tsukamoto R， et al. Nicotinamide blocks N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis in rats through poly （ADP-ribose） polymerase activity and Jun N-terminal kinase/activator protein-1 pathway inhibition[J]. Exp Eye Res，2006，82（3）：488-495.
[15]
Yang JN， Chen JM， Luo L， et al. Tetramethylpyrazine protected photoreceptor cells of rats by modulating nuclear translocation of NF-kappaB[J]. Acta Pharmacol Sin，2005，26（7）：887-892.
浙公网安备 33030202001892号