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

Qi Zhang, Helen Vuong, Xin Huang, Yan Ling Wang, Nicholas C. Brecha, Ming Liang Pu, Jie Gao

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21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)720-730
Number of pages11
JournalScience China Life Sciences
Volume56
Issue number8
DOIs
StatePublished - Aug 2013

Bibliographical note

Funding Information:
This work was supported by the National Basic Research Program of China (2009CB320900 to Pu MingLiang, 2011CB510206 to Pu MingLiang and Gao Jie), National Natural Science Foundation of China (30831160516 to Pu MingLiang), NIH EY04067 (N.C. Brecha), and VA Merit Review (N.C. Brecha). N.C. Brecha is a VA Career Research Scientist. H. Vuong was supported by a summer fellowship from the PKU-UCLA Joint Research Institute.

Keywords

  • Thy1-CFP-DBA/2J mouse
  • depression
  • melanopsin-expressing retinal ganglion cells
  • pigmentary glaucoma
  • retinal ganglion cells

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