Transplanted olfactory ensheathing cells reduce retinal degeneration in Royal College of Surgeons rats.
OBJECTIVE
Retinitis pigmentosa (RP) is a group of genetic disorders and a slow loss of vision that is caused by a cascade of retinal degenerative events. We examined whether these retinal degenerative events were reduced after cultured mixtures of adult olfactory ensheathing cells (OECs) and olfactory nerve fibroblasts (ONFs) were transplanted into the subretinal space of 1-month-old RCS rat, a classic model of RP.


METHODS
The changes in retinal photoreceptors and Müller cells of RCS rats after cell transplantation were observed by the expression of recoverin and glial fibrillary acidic protein (GFAP), counting peanut agglutinin (PNA)-positive cone outer segments and calculating the relative apoptotic area. The retinal function was also evaluated by Flash electroretinography (ERG). To further investigate the mechanisms, by which OECs/ONFs play important roles in the transplanted retinas, nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and basic fibroblast growth factor (bFGF) secretion of the cultured cells were analyzed by ELISA. The ability of OECs/ONFs to ingest porcine retinal outer segments and the amount of phagocytosis were compared with retinal pigment epithelium (RPE) cells.


RESULTS
Our research showed that the transplantation of OECs/ONFs mixtures restored recoverin expression, protected retinal outer segments, increased PNA-positive cone outer segments, reduced caspase-positive apoptotic figures, downregulated GFAP, and maintained the b-wave of the ERG. Cultured OECs/ONFs expressed and secreted NGF, BDNF, and bFGF which made contributions to assist survival of the photoreceptors. An in vitro phagocytosis assay showed that OECs, but not ONFs, phagocytosed porcine retinal outer segments, and the phagocytic ability of OECs was even superior to that of RPE cells.


CONCLUSIONS
These findings demonstrate that transplantation of OECs/ONFs cleaned up the accumulated debris in subretinal space, and provided an intrinsic continuous supply of neurotrophic factors. It suggested that transplantation of OECs/ONFs might be a possible future route for protection of the retina and reducing retinal degeneration in RP.
Southwest Hospital/Southwest Eye Hospital, Third Military Medical University, Chong Qing, China.
Shu Jia
SJ
Huo
Yao Chen
YC
Li
Jing
J
Xie
Ying
Y
Li
Geoffrey
G
Raisman
Yu Xiao
YX
Zeng
Jian Rong
JR
He
Chuan Huang
CH
Weng
Zheng Qin
ZQ
Yin
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002470:Cell Survival; D017690:Cell Transplantation; D004195:Disease Models, Animal; D004596:Electroretinography; D004797:Enzyme-Linked Immunosorbent Assay; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000637:transplantation*; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism; D058953:Neural Stem Cells / Q000637:transplantation*; D009830:Olfactory Bulb / Q000166:cytology*; D009832:Olfactory Nerve / Q000166:cytology; D010587:Phagocytosis / Q000502:physiology; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011922:Rats, Mutant Strains; D051603:Recoverin / Q000378:metabolism; D012160:Retina / Q000502:physiology; D055351:Retinal Neurons / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D013552:Swine; D014162:Transfection
D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; C496733:Rcvrn protein, rat; D016222:Fibroblast Growth Factor 2; D051603:Recoverin; D020932:Nerve Growth Factor