Apoptosis of optic nerve cells after retinal contusion injury in rabbits

doi:10.3969/j.issn.2095-4344.2014.18.011

Abstract

Abstract:

BACKGROUND: Retinal contusion injury is one of the leading causes for vision impairment, and clinical treatment is difficult. Although fundus change after retinal contusion injury has been fully understood, the pathogenesis and drug treatment still remain controversial.
OBJECTIVE: To explore the apoptosis and related mechanism of optic nerve cells in rabbit model of retinal contusion injury.
METHODS: Forty-eight healthy adult rabbits without oculopathy were divided into eight groups: 1 hour, 3 hours,
1 day, 3 days, 7 days, 14 days, 28 days after contusion and normal control, with six rabbits in each group. Right eye of each rabbit was treated with Allen’s reformative hitting method as contusive retinopathy model. The eyeballs were enucleated at different time points after injury in rabbit retina. The pathological section of optic nerve 5 mm posterior to sieve plate was harvested. The morphologic changes of optic nerve were observed and number of glial cells was measured using hematoxylin-eosin staining. Electron microscope and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling technique were used to assess apoptosis.
RESULTS AND CONCLUSION: In the normal control group, glial cells presented cylinder shapes and neural fibers arranged neatly. The trend of the glial cells was as the same as the neural fibers. But the optic nerve fibers arranged in disorder and the glial cells lost polarity in the groups of 1 hour, 3 hours, 1 day, 3 days, 7 days after retinal contusion injury. The number of glial cells in 1 hour, 3 hours, 1 day, 3 days, 7 days, 14 days, and 28 days was extremely significantly reduced compared with normal control group (P < 0.01). There was cell apoptosis in
optic nerve after retinal contusion injury, but almost not observed in optic nerve from normal control group, 1 hour and
28 days after injury. The apoptotic cells were abundant at 3 hours, 1 day, 3 days, 7 days, 14 days after injury, and peaked at 3 days, showing extremely significant differences compared with normal control group (P < 0.01). Apoptosis occurs in optic nerve after contusion of retina, which may be one of the reasons for incomplete recovery of retinal function.

中国组织工程研究杂志出版内容重点：肾移植；肝移植；移植；心脏移植；组织移植；皮肤移植；皮瓣移植；血管移植；器官移植；组织工程

全文链接：

Key words: retina, optic nerve, neuroglia, apoptosis, models, animal

CLC Number:

R318

Wang Zhi-yu, Shi Ai-yun. Apoptosis of optic nerve cells after retinal contusion injury in rabbits[J]. Chinese Journal of Tissue Engineering Research, 2014, 18(18): 2848-2854.

Figures/Tables 2

References

[1] 刘家琦,李凤鸣.实用眼科学[M].2版.北京:人民卫生出版社,2003: 583.
[2] Sipperley JQ, Quigley HA, Hass JDM. Traumatic retinopathy of prematurity in primates; the explanation of commotio retinae.Arch Ophthalmol. 1978;96: 2267-2273.
[3] Chakravarthy U, Douglas AJ, Bailie R, et al. Immnoreactive endothelin distribution in ocular tissues. Invest Opthhalmol Vis Sci. 1994;35:2448.
[4] Chen CS, Odel JG, Miller JS, et al.Multifocal visual evoked potentials and multifocal electroretinograms in papillorenal syndrome. Arch Ophthalmol. 2002; 120(6): 870-871.
[5] 窦宏亮,宋琛.眼球挫伤后眼血流动力学改变[J].中华眼科杂志, 1992,28(4): 243-245.
[6] 安美霞,张效房,张金嵩.挫伤性视网膜病变中光感受器细胞凋亡与氧化损伤的实验研究[J].中华眼科杂志,2004,40(2): 118-121.
[7] Yang L, Bula D, Arroyo JG, et al. Preventing retinal detachment- associated photoreceptor cell loss in Bax-deficient mice. Invest Ophthalmol Vis Sci. 2004;45(2): 648-654.
[8] Seddon JM, Cote J, Page WF, et al. The US twin study of age-related macular degeneration: relative roles of genetic and environmental influences. Arch Ophthalmol. 2005;123: 321-327.
[9] Tomany SC, Cruickshanks KJ, Klein R, et al. Sunlight and the 10-year incidence of age-related maculopathy: the beaver dam eye study. Arch Ophthalmol. 2004;122: 750-757.
[10] 李凤鸣.眼科全书下册[M].2版.北京:人民卫生出版社,1996: 3281-3285.
[11] 王志玉,付群,史爱云.视网膜挫伤后神经感觉层细胞凋亡的实验研究[J].眼科新进展, 2008,28(8):590-594.
[12] Wenzel A, Grimm C, Samardzija M, et al. Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog Retin Eye Res. 2005;24(2):275-306.
[13] Zacks DN, Hanninen V, Pantcheva M, et al. Caspase activation in an experimental model of retinal detachment. Invest Ophthalmol Vis Sci. 2003;44(3):1262-1267.
[14] Peter ME, Heufelder AE, Hengartner MO. Advances in apoptosis research. Proc Natl Acad Sci USA. 1997;94(24): 12736-12737.
[15] 欧阳科,袁援生,李燕.大鼠青光眼模型视网膜神经节细胞凋亡的研究[J].眼科研究, 2008,26(10): 725-725.
[16] 张琳琳,吕瀛娟,于荣国,等.标准化大鼠外伤性视神经损伤动物模型建立[J].眼外伤职业眼病杂志,2008, 30(12): 913-917.
[17] Hisatomi T, Sakamoto T, Murata T, et al. Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo. Am J Pathol. 2001;158(4): 1271-1278.
[18] Nakano Y, Oyamada M, Dai P, et al. Connexin43 knockdown accelerates wound healing but inhibits mesenchymal transition after corneal endothelial injury in vivo. Invest Ophthalmol Vis Sci. 2008;49(1):93-104.
[19] Zhang Y, Wang W. Effects of bone marrow mesenchymal stem cell transplantation on light damaged retina. Invest Ophthalmol Vis Sci. 2010;51(7): 3742-3748.
[20] Calera MR,Wang Z,Sanchez-Olea R,et al.Depression of intraocular pressure following inactivation of connexin43 in the nonpigmented epithelium of theciliary body. Invest Ophthalmol Vis Sci.2009;50(5):2185-2193.
[21] Bak M, Silahtaroglu A, Moller M, et al. MicroRNA expression in the adult mouse central nervous system. RNA. 2008;14(3): 432-444.
[22] 徐格致,李维英,曹安民.老年黄斑变性中感光细胞的凋亡[J].中华眼科杂志,1998,34(1):59-61.
[23] Monteiro BG, Serafim RC, Melo GB, et al. Human immature dental pulp stem cells share key characteristic features with limbal stem cells. Cell Prolif. 2009;42(5):587-594.
[24] Navaratna D, Menicucci G, Maestas J, et al. A peptideinhibitor of the uPA / uPAR system inhibits alteration of the blood retinal barrier in diabetes. FASEB J. 2008;22(9) : 3310-3317.
[25] Leal EC, Aveleira CA, Castilho AF, et al. High glucose and oxidative /nitrosative stress conditions induce apoptosis in retinal endothelial cells by a caspase-independent pathway. Exp Eye Res. 2009;88(5) : 983-991.
[26] Romeo G, Liu WH, Asnaghi V, et al. Activation of nuclear factor kappa B induced by diabetes and high glucose regulates a proapoptotic program in retinal pericytes. Diabetes. 2002; 51(7) : 2241-2248.
[27] Ejaz S, Chekarova I, Ejaz A, et al. Importance of pericytes and mechanisms of pericyte loss during diabetes retinopathy. Diabetes Obes Metab. 2008;10(1): 53-63.
[28] Loscher CJ, Hokamp K, Wilson JH, et al. A common microRNA signature in mouse models of retina l degeneration. Exp Eye Res. 2008;87 (6) : 5292534.
[29] Damiani D, Alexander JJ, O ’Rourke JR, et al. Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. Neuroscience. 2008; 28(19) : 4878-4887.
[30] Ueki Y,Wang J, Chollangi S, et al. STAT3 activation in photoreceptors by leukemia inhibitory factor is associated with protection from light damage. J Neurochem. 2008;105 (3): 784-796.
[31] Cong LD, Sun DW, Zhang ZY, et al. A novel rabbit model for studying RPE transplantation. Invest Ophthalmol Vis Sci. 2008; 49(9):4115-4125.
[32] Lee JK, Jin HK, Bae JS. Bone marrow derived mesenchymal stem cells attenuate amyloid beta2 induced memoryimpa irmentand apoptosis by inhibiting neuronal cell death. Curr Alzheimer Res. 2010;7(6):540-548.
[33] Mu H, Zhang XM, Liu JJ, et al.Effect of high glucose concentration on VEGF and PEDF express ion in cultured retinal Müller cells. Mol Biol Rep. 2009;36(8): 2147-2151.
[34] Joly S, Lange C, Thiersch M, et al. Leukemia inhiitory factor extends the life span of injured photoreceptors in vivo. J Neurosci. 2008;28 (51) : 13765-13774.
[35] Petrovic MG, Korosec P, Kosnik M, et al. Local and genetic determinants of vascular endothelial growth factor expression in advanced proliferative diabetic retinopathy. Mol Vis. 2008; 14: 1382-1387.
[36] Loewen N, Chen J, Dudley VJ, et al.Genomic response of hypoxic Müller cells involves the very low density lipoprote in receptor as part of an angiogenic network. Exp Eye Res. 2009; 88(5):928-937.
[37] Loscher CJ, Hokamp K, Wilson JH, et al. A common microRNA signature in mouse models of retina l degeneration. Exp Eye Res. 2008;87(6):529-534.
[38] 王雨生,李蓉.胶质细胞在眼内疾病发生和视网膜功能重建中的作用[J].眼科国际纵览,2010,34(6):361-363.
[39] Nakazawa T, Takeda M, Lewis GP, et al. Attenuated glial reactions and photoreceptor degeneration after retina l detachment in mice deficient in glial fibrillary acidic protein and vimentin. Invest Ophthalmol Vis Sci. 2007;48(6) : 2760-2768.
[40] Yan F, Hui YN, Li YJ. Epidermal growth factor receptor in cultured human retinal pigment epithelial cells. Ophthalmologica. 2007;221(4):244-250.
[41] Shen J, Yang X, Xie B, et al. MicroRNAs regulate ocular neovascularization. Mol Ther. 2008;16(7) : 1208-1216.
[42] Hisatomi T, Sakamoto T, Goto Y, et al. Critical role of photoreceptor apoptosis in functional damage after retinaldetachment. Curr Eye Res. 2002;24:161-172.
[43] Chang CJ, Lai WW, Edward DP, et al. Apoptotic photoreceptor cell death after traumatic retinal detachment in humans. Arch Ophthalmol. 1995;113(7):880-886.
[44] Nakazawa T, Takeda M, Lewis GP, et al. Attenuated glia l reactions and photoreceptor degeneration after retina l detachment in mice deficient in glial fibrillary acidic protein and vimentin. Invest Ophthalmol Vis Sci. 2007;48(6) : 2760-2768.
[45] Zhao Y, Hong DH, Pawlyk B, et al. The retinitis pigmentosa GTPase regulator (RPGR)-interacting protein: subserving RPGR function1 and participating in disk morphogenesis. Proc Natl Acad Sci USA. 2003;100:3965-3970.
[46] Lam TT, Abler AS, Tso MM, et al. Apoptosis and caspases after ischemia-reperfusion injury in rat retina. Invest Ophthalmol Vis Sci. 1999;40(5):967-975.