Expression and function of receptors for advanced glycation end products in bovine corneal endothelial cells.
OBJECTIVE
The corneal endothelium is a target of the aging process. This study was undertaken to reveal the relationship between corneal endothelial cell (CEC) death and the accumulation of advanced glycation end products (AGEs), by investigating the possible mechanism of accumulation of AGE in CECs and its effects on CEC death.


METHODS
First, the in vivo expression of the receptor was investigated for AGE (RAGE) and galectin-3, both receptors for AGE, at both the mRNA and protein levels. Second, AGEs were added to the culture media of the cultured CECs, and the uptake of AGEs, the generation of reactive oxygen species, and the induction of apoptosis were investigated.


RESULTS
Immunohistochemistry and RT-PCR demonstrated that both RAGE and galectin-3 were expressed in bovine CECs. After administration of AGE-modified bovine serum albumin to the culture medium, uptake of AGE was observed in the cytoplasm of the cultured bovine CECs. In addition, with increasing concentration of AGEs, the generation of reactive oxygen and the number of apoptotic cells also increased.


CONCLUSIONS
These results show that the accumulation of AGEs in CECs induced apoptosis, in part, by increasing cellular oxidative stress. The accumulation of AGEs in the CECs of elderly patients may be involved in the loss of CECs during the aging process.
Kaji
Yuichi
Y
Department of Ophthalmology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Amano
Shiro
S
Usui
Tomohiko
T
Oshika
Tetsuro
T
Yamashiro
Kenji
K
Ishida
Susumu
S
Suzuki
Kaori
K
Tanaka
Sumiyoshi
S
Adamis
Anthony P
AP
Nagai
Ryoji
R
Horiuchi
Seiko
S
D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D004728:Endothelium, Corneal / Q000378:metabolism* / Q000473:pathology; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D011975:Receptors, Mitogen / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D037502:Galectin 3; D017127:Glycation End Products, Advanced; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011975:Receptors, Mitogen; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine