Protection of retinal ganglion cells against glaucomatous neuropathy by neurotrophin-producing, genetically modified neural progenitor cells in a rat model.
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.
Wang
Ningli
N
Zhongshan Ophthalmic Center, Zhongshan University, Guangzhou 510060, China. ningliw@hotmail.com
Zeng
Mingbing
M
Ruan
Yiwen
Y
Wu
Heping
H
Chen
Jingchang
J
Fan
Zhigang
Z
Zhen
Huling
H
D000818:Animals; D017209:Apoptosis; D001370:Axonal Transport; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002470:Cell Survival; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005901:Glaucoma / Q000628:therapy*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012165:Retinal Ganglion Cells / Q000166:cytology*; D013234:Stem Cells / Q000502:physiology*; D014822:Vitreous Body / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor