PMID- 12411121 OWN - NLM STAT- MEDLINE DCOM- 20021122 LR - 20121115 IS - 0366-6999 (Print) IS - 0366-6999 (Linking) VI - 115 IP - 9 DP - 2002 Sep TI - Protection of retinal ganglion cells against glaucomatous neuropathy by neurotrophin-producing, genetically modified neural progenitor cells in a rat model. PG - 1394-400 AB - OBJECTIVE: To investigate in vivo survival of retinal ganglion cells (RGCs) after partial blockage of optic nerve (ON) axoplasmic flow by sub-retinal 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 labeled with granular blue (GB) applied to their main targets in the brain. Seven days later, the left ON was intra-obitally 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 was 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 intra-vitreous injection of BDNF-NPC was 2101 +/- 15, 1809 +/- 19 and 1625 +/- 34. Similar results were found in groups after sub-retinal injection. Higher densities were observed in groups treated with BDNF-NPCs. There were statistically significant differences among groups through 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. FAU - Wang, Ningli AU - Wang N AD - Zhongshan Ophthalmic Center, Zhongshan University, Guangzhou 510060, China. ningliw@hotmail.com FAU - Zeng, Mingbing AU - Zeng M FAU - Ruan, Yiwen AU - Ruan Y FAU - Wu, Heping AU - Wu H FAU - Chen, Jingchang AU - Chen J FAU - Fan, Zhigang AU - Fan Z FAU - Zhen, Huling AU - Zhen H LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Chin Med J (Engl) JT - Chinese medical journal JID - 7513795 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Apoptosis MH - Axonal Transport MH - Brain-Derived Neurotrophic Factor/*genetics MH - Cell Survival MH - Gene Transfer Techniques MH - *Genetic Therapy MH - Glaucoma/*therapy MH - Male MH - Rats MH - Rats, Sprague-Dawley MH - Retinal Ganglion Cells/*cytology MH - Stem Cells/*physiology MH - Vitreous Body/metabolism EDAT- 2002/11/02 04:00 MHDA- 2002/11/26 04:00 CRDT- 2002/11/02 04:00 PHST- 2002/11/02 04:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/11/02 04:00 [entrez] PST - ppublish SO - Chin Med J (Engl). 2002 Sep;115(9):1394-400.