IOVS Proceedings of the National Academy of Sciences
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(Investigative Ophthalmology and Visual Science. 2005;46:1497-1503.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.04-0664
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CNTF and BDNF Have Similar Effects on Retinal Ganglion Cell Survival but Differential Effects on Nitric Oxide Synthase Expression Soon after Optic Nerve Injury

Cheng-Wu Zhang,1 Qiang Lu,2,3 Si-Wei You,2,4 Ye Zhi,1 Henry K. Yip,2 Wutian Wu,2 Kwok-Fai So,2 and Qi Cui1,5,6

1From the Laboratory for Neural Repair, Shantou University Medical College, Shantou, People’s Republic of China; the 2Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; the 5School of Anatomy and Human Biology and the 6Western Australian Institute for Medical Research, The University of Western Australia, Crawley, Australia.

PURPOSE. To investigate the effect of ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) on retinal ganglion cell (RGC) survival and nitric oxide synthase (NOS) expression in the retina during the early phase of optic nerve (ON) injury, and to examine whether intraperitoneal application of the NOS scavenger nitro-L-arginine (L-NA) could protect the injured RGCs.

METHODS. RGCs were retrogradely labeled with granular blue 3 days before the ON was intraorbitally transected. RGC survival was examined 1 week after ON transection and intraocular injection of CNTF and/or BDNF, or 1 to 2 weeks after daily intraperitoneal injection of the NOS inhibitor L-NA. NOS expression was examined by NADPH-diaphorase histochemistry and neuronal NOS (nNOS) immunohistochemistry, and nNOS-positive cells were identified by various staining approaches.

RESULTS. Both CNTF and BDNF significantly increased RGC survival 1 week after ON injury. In the ganglion cell layer (GCL), CNTF did not increase the number of NADPH-diaphorase positive (+) cells but appeared to reduce the intensity of NADPH-diaphorase staining, whereas BDNF increased the number of NADPH-diaphorase+ cells and also appeared to enhance the intensity of NADPH-diaphorase staining. In the GCL, amacrine cells but not RGCs were nNOS+. Some macrophages were also nNOS+. In contrast, no amacrine cells were nNOS+ in the inner nuclear layer. Daily intraperitoneal injection of L-NA at appropriate concentrations promoted RGC survival for 1 or 2 weeks after ON injury.

CONCLUSIONS. Both CNTF and BDNF protected RGCs after ON injury. CNTF and BDNF acted differently on NOS expression in the GCL. Intraperitoneal injections of L-NA at appropriate dosages enhance RGC survival.




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