Gene transfer of cyto-protective molecules in corneal endothelial cells and cultured corneas: analysis of protective effects in vitro and in vivo.
The loss of corneal endothelial cells plays a critical role in many corneal diseases and is a common phenomenon following cornea transplantation. In addition, the non-regenerative capacity of human corneal endothelial cells (HCEC) ultimately requires appropriate protection of corneal tissues during ex vivo storage to ensure vitality of the cells. However, only 70% of donor corneas can be used for grafting because of endothelial deficiencies. Corneal endothelial cell loss during storage is mainly induced by apoptotic cell death. This study was undertaken, for proof of principle, to investigate whether over-expression of cyto-protective molecules Bcl-x(L), Bag-1, and HO-1 prevents the loss of corneal endothelial cells both in vitro and in vivo. We demonstrate that gene transfer of both Bcl-x(L) and HO-1 has cyto-protective effects on HCEC in vitro. However, gene transfer of a single cyto-protective molecule does not prevent its rejection upon transplantation in a MHC class I/II disparate rat model.
Gong
Nianqiao
N
Department of Ophthalmology, Charité-University Medicine Berlin, Germany.
Ecke
Ines
I
Mergler
Stefan
S
Yang
Jun
J
Metzner
Sylvia
S
Schu
Sabine
S
Volk
Hans-Dieter
HD
Pleyer
Uwe
U
Ritter
Thomas
T
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D016039:Corneal Transplantation / Q000379:methods*; D019610:Cytoprotection / Q000502:physiology*; D004728:Endothelium, Corneal / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D005260:Female; D018014:Gene Transfer Techniques; D006085:Graft Survival / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism*
C494811:BCL2L1 protein, human; D051020:bcl-X Protein; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1