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Abstract #8063 Published in IGR 4-3

Protection of retinal ganglion cells against glaucomatous neuropathy by neurotrophin-producing, genetically modified neural progenitor cells in a rat model

Wang N; Zeng M; Ruan Y; Wu H; Chen J; Fan Z; Zhen H
Chinese Medical Journal 2002; 115: 1394-1400


OBJECTIVE: To investigate the in vivo survival of retinal ganglion cells (RGCs) after partial blockage of optic nerve (ON) axoplasmic flow by subretinal space or vitreous cavity injection of brain-derived neural factor (BDNF) produced by genetically modified neural progenitor cells (NPCs). METHODS: Adult Sprague-Dawley (SD) rat RGCs were labelled with granular blue (GB) applied to their main targets in the brain. Seven days later, the left ON was intra-orbitally crushed with a 40-g power forceps to partially block ON axoplasmic flow. Animals were randomized to three groups. The left eye of each rat received a sham injection, NPCs injection, or an injection of genetically modified neural progenitors producing BDNF (BDNF-NPCs). Seven, 15, and 30 days after ON crush, retinas were examined under a fluorescence microscope. By calculating and comparing the average RGCs densities and RGC apoptosis density, RGC survival was estimated, and the neuro-protective effect of transplanted cells evaluated. RESULTS: Seven, 15, and 30 days after crush, in the intra-vitreous injection group, mean RGC densities had decreased to 1885 68, 1562 20, 1380 7 and 1837 46, 1561 58, 1370 16, respectively, with sham injection or neural progenitors injection. However, RGCs density in the groups treated with intravitreous injection of BDNF-NPC was 2101 15, 1809 19 and 1625 34. Similar results were found in groups after subretinal injection. Higher densities were observed in groups treated with BDNF-NPCs. There were statistically significant differences between groups on nonparametric tests followed by the Mann-Whitely test. RGC apoptosis density in BDNF-NPC at each follow-up time was less than in other groups. CONCLUSIONS: A continuous supply of neurotrophic factors by the injection of genetically modified neural progenitors presents a highly effective approach to counteract optic neuropathy and RGC degeneration after partial ON axoplasmic flow blockage.

N. Wang, MD, Zhongshan Ophthalmic Center, Zhongshan University, Guangzhou 510060, China. ningliw@hotmail.com


Classification:

11.8 Neuroprotection (Part of: 11 Medical treatment)



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