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Altered Expression of nNOS/NIDD in the Retina of a Glaucoma Model of DBA/2J Mice and the Intervention by nNOS Inhibition

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Abstract

The NIDD gene, neuronal NOS (nNOS)-interacting DHHC domain-containing protein with dendritic mRNA, codes a protein that upregulates nNOS enzyme activity by the interaction with the postsynaptic density protein 95/discsslarge/zon occlusens-1 (PDZ) domain of nNOS. Glial cell activation, especially Müller cells, may be an important factor contributing to retinal ganglion cell (RGC) death in glaucoma. The present study was to measure nNOS and NIDD expression in DBA/2J mice, a mouse model of glaucoma, and their correlation with glaucomatous phenotypes. Slit-lamp biomicroscopy, fundus photography, intraocular pressure (IOP) measurement, histology, and optic nerve axon counts were used to examine the ocular phenotypes of DBA/2J mice. Quantitative real-time PCR(RT-PCR) and Western blot analysis were used to analyze mRNA and protein expression of nNOS and NIDD. Their spatial distribution was evaluated by immunohistochemistry. Immunofluorescence was performed to observe the colocalization of nNOS and NIDD and the association of NIDD with Müller cells. The results showed that the prevalence and severity of ocular abnormalities, IOP, optic nerve cupping, and optic nerve atrophy increased with age. The mRNA and protein expression of nNOS reached the peak at 9 months old. The protein of NIDD underwent a similar change, while the mRNA of NIDD significantly increased at 6 months old. The expression of NIDD physically coexisted with nNOS in Müller cells. Administration of NOS inhibitor NG-Nitro-l-arginine-methyl-ester (L-NAME) by intraperitoneal injection (i.p.) prevented RGCs from apoptosis as shown in the increase of Brn-3a (RGC marker) expression, which was accompanied by decreased expression of NIDD. The spatiotemporal changes of nNOS/NIDD expression and its interference suggest that NIDD–nNOS axis may play a role in the degenerative process of RGC in glaucoma.

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Acknowledgments

We are grateful to Jingsheng Tuo for critical reading of the manuscript. The authors thank all the members of eye laboratory in the Affiliated Hospital of Nantong University. The study was supported by the Natural Science Foundation of Jiangsu China (Grant No. BK2008186) and Science Foundation of Nantong China (Grant No. HS2011005).

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Authors and Affiliations

  1. Eye Institute, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, 226001, People’s Republic of China

    Chen Chen, Yue Xu, Jindi Zhang, Juming Zhu, Junfang Zhang, Nan Hu & Huaijin Guan

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  1. Chen Chen
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  2. Yue Xu
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  3. Jindi Zhang
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  4. Juming Zhu
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  5. Junfang Zhang
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  6. Nan Hu
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  7. Huaijin Guan
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Correspondence to Huaijin Guan.

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Chen Chen and Yue Xu contributed equally to this work.

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Chen, C., Xu, Y., Zhang, J. et al. Altered Expression of nNOS/NIDD in the Retina of a Glaucoma Model of DBA/2J Mice and the Intervention by nNOS Inhibition. J Mol Neurosci 51, 47–56 (2013). https://doi.org/10.1007/s12031-012-9943-x

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  • DOI: https://doi.org/10.1007/s12031-012-9943-x

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