Melanopsin-expressing retinal ganglion cell loss and behavioral analysis in the Thy1-CFP-DBA/2J mouse model of glaucoma  

作　　者：ZHANG Qi VUONG Helen HUANG Xin WANG YanLing BRECHA Nicholas C. PU MingLiang GAO Jie 

机构地区：[1]Department of Anatomy,School of Basic Medical Sciences,Peking University [2]Key Laboratory on Machine Perception(Ministry of Education),Peking University [3]Key Laboratory for Visual Impairment and Restoration(Ministry of Education),Peking University [4]Department of Neurobiology and Molecular,Cellular,and Integrative Physiology,University of California,Los Angeles,CA 90095,USA [5]Jules Stein Eye Institute,University of California,Los Angeles,CA 90095,USA [6]UCLA College of Life Sciences,University of California,Los Angeles,CA 90095,USA

出　　处：《Science China(Life Sciences)》2013年第8期720-730,共11页中国科学（生命科学英文版）

基　　金：supported by the National Basic Research Program of China (2009CB320900 to Pu MingLiang,2011CB510206 to Pu MingLiangand Gao Jie);National Natural Science Foundation of China(30831160516 to Pu MingLiang);NIH EY04067 (N.C. Brecha);VAMerit Review (N.C. Brecha).;supported by a summer fellowship from the PKU-UCLA Joint Research Institute

摘　　要：In this study, the role of melanopsin-expressing retinal ganglion cells （mRGCs） in the glaucoma-induced depressive behavioral response pattern was investigated. The CFP-D2 transgenic glaucoma animal model from five age groups was used in this study. Immunohistochemical labeling, quantitative analysis of mRGC morphology, open field test （OFT）, and statistical analysis were used. In comparison with C57 BL/6 mice, the age-matched CFP-D2 mice had significantly elevated intraocular pressure （lOP）. We observed parallel morphological changes in the retina, including a reduction in the density of cyan fluorescent protein- （CFP） expressing cells （cells mm^-2 at 2 months of age, 1309±26; 14 months, 878±30, P〈0.001）, mRGCs （2 months, 48_＋3; 14 months, 19±4, P〈0.001）, Brn3b-expressing RGCs （2 months, 1283±80; 14 months, 950±31, P〈0.001）, Brn-3b expressing mRGCs （5 months, 50.17%±5.5%; 14 months, 12.61%±3.8%, P〈0.001）, and reduction in the dendritic field size of mRGCs （mm^2 at 2 months, 0.077±0.015; 14 months, 0.065±0.015, P〈0.05）. CFP-D2 mice had hyperactive locomotor activity patterns based on OFT findings of the total distance traveled, number of entries into the center, and time spent in the center of the testing apparatus. The glaucoma induced hyperactive response pattern could be associated with dysfunctional mRGCs, most likely Brn-3b-positive mRGCs in CFP-D2 mice.In this study,the role of melanopsin-expressing retinal ganglion cells(mRGCs) in the glaucoma-induced depressive behavioral response pattern was investigated.The CFP-D2 transgenic glaucoma animal model from five age groups was used in this study.Immunohistochemical labeling,quantitative analysis of mRGC morphology,open field test(OFT),and statistical analysis were used.In comparison with C57 BL/6 mice,the age-matched CFP-D2 mice had significantly elevated intraocular pressure(IOP).We observed parallel morphological changes in the retina,including a reduction in the density of cyan fluorescent protein(CFP) expressing cells(cells mm 2 at 2 months of age,1309±26;14 months,878±30,P<0.001),mRGCs(2 months,48±3;14 months,19±4,P<0.001),Brn3b-expressing RGCs(2 months,1283±80;14 months,950±31,P<0.001),Brn-3b expressing mRGCs(5 months,50.17%±5.5%;14 months,12.61%±3.8%,P<0.001),and reduction in the dendritic field size of mRGCs(mm2 at 2 months,0.077±0.015;14 months,0.065±0.015,P<0.05).CFP-D2 mice had hyperactive locomotor activity patterns based on OFT findings of the total distance traveled,number of entries into the center,and time spent in the center of the testing apparatus.The glaucoma induced hyperactive response pattern could be associated with dysfunctional mRGCs,most likely Brn-3b-positive mRGCs in CFP-D2 mice.

关 键 词：pigmentary glaucoma Thyl-CFP-DBA/2J mouse retinal ganglion cells melanopsin-expressing retinal ganglion cells depression 

分 类 号：R775[医药卫生—眼科]