TY - JOUR
T1 - Retinal pigment epithelial cells secrete neurotrophic factors and synthesize dopamine
T2 - Possible contribution to therapeutic effects of RPE cell transplantation in Parkinson's disease
AU - Ming, Ming
AU - Li, Xuping
AU - Fan, Xiaolan
AU - Yang, Dehua
AU - Li, Liang
AU - Chen, Sheng
AU - Gu, Qing
AU - Le, Weidong
N1 - Funding Information:
This work was supported by a grant from 973 National Project (NO. 2005CB724302), the National Natural Science Foundation (NO. 30730096), the National Basic Research Program of China from Science and Technology Commission (NO. 2007CB947904) and the Technology Commission (863 project 2007AA02Z460).
PY - 2009/6/28
Y1 - 2009/6/28
N2 - Background: New strategies for the treatment of Parkinson's disease (PD) are shifted from dopamine (DA) replacement to regeneration or restoration of the nigro-striatal system. A cell therapy using human retinal pigment epithelial (RPE) cells as substitution for degenerated dopaminergic (DAergic) neurons has been developed and showed promising prospect in clinical treatment of PD, but the exact mechanism underlying this therapy is not fully elucidated. In the present study, we investigated whether the beneficial effects of this therapy are related to the trophic properties of RPE cells and their ability to synthesize DA. Methods: We evaluated the protective effects of conditioned medium (CM) from cultured RPE cells on the DAergic cells against 6-hydroxydopamine (6-OHDA)- and rotenone-induced neurotoxicity and determined the levels of glial cell derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) released by RPE cells. We also measured the DA synthesis and release. Finally we transplanted microcarriers-RPE cells into 6-OHDA lesioned rats and observed the improvement in apomorphine-induced rotations (AIR). Results: We report here: (1) CM from RPE cells can secret trophic factors GDNF and BDNF, and protect DAergic neurons against the 6-OHDA- and rotenone-induced cell injury; (2) cultured RPE cells express L-dopa decarboxylase (DDC) and synthesize DA; (3) RPE cells attached to microcarriers can survive in the host striatum and improve the AIR in 6-OHDA-lesioned animal model of PD; (4) GDNF and BDNF levels are found significantly higher in the RPE cell-grafted tissues. Conclusion: These findings indicate the RPE cells have the ability to secret GDNF and BDNF, and synthesize DA, which probably contribute to the therapeutic effects of RPE cell transplantation in PD.
AB - Background: New strategies for the treatment of Parkinson's disease (PD) are shifted from dopamine (DA) replacement to regeneration or restoration of the nigro-striatal system. A cell therapy using human retinal pigment epithelial (RPE) cells as substitution for degenerated dopaminergic (DAergic) neurons has been developed and showed promising prospect in clinical treatment of PD, but the exact mechanism underlying this therapy is not fully elucidated. In the present study, we investigated whether the beneficial effects of this therapy are related to the trophic properties of RPE cells and their ability to synthesize DA. Methods: We evaluated the protective effects of conditioned medium (CM) from cultured RPE cells on the DAergic cells against 6-hydroxydopamine (6-OHDA)- and rotenone-induced neurotoxicity and determined the levels of glial cell derived neurotrophic factor (GDNF) and brain derived neurotrophic factor (BDNF) released by RPE cells. We also measured the DA synthesis and release. Finally we transplanted microcarriers-RPE cells into 6-OHDA lesioned rats and observed the improvement in apomorphine-induced rotations (AIR). Results: We report here: (1) CM from RPE cells can secret trophic factors GDNF and BDNF, and protect DAergic neurons against the 6-OHDA- and rotenone-induced cell injury; (2) cultured RPE cells express L-dopa decarboxylase (DDC) and synthesize DA; (3) RPE cells attached to microcarriers can survive in the host striatum and improve the AIR in 6-OHDA-lesioned animal model of PD; (4) GDNF and BDNF levels are found significantly higher in the RPE cell-grafted tissues. Conclusion: These findings indicate the RPE cells have the ability to secret GDNF and BDNF, and synthesize DA, which probably contribute to the therapeutic effects of RPE cell transplantation in PD.
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U2 - 10.1186/1479-5876-7-53
DO - 10.1186/1479-5876-7-53
M3 - Article
C2 - 19558709
AN - SCOPUS:67651043684
VL - 7
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
SN - 1479-5876
M1 - 53
ER -