Regulation of indoleamine 2,3-dioxygenase, the first enzyme in UV filter biosynthesis in the human lens. Relevance for senile nuclear cataract.
3-Hydroxykynurenine (3OHKyn), the precursor of UV filters in human lens, is highly autooxidizable, generates H2O2, and binds to lens proteins, yielding a tanned/yellow product resembling senile nuclear cataractous materials. Thus, if 3OHkyn can be shown to be the causative agent in cataract, it may be possible to prevent the disease by lowering the level of 3OHKyn. To this end, indoleamine 2,3-dioxygenase, the first enzyme in UV filter synthesis, was studied using lens epithelial cell lines. The results indicated that the IDO expression is mediated by IFN-gamma. Immuno-suppressants which inhibit production of IFN-gamma may act as anti-cataract agents. Another way to lower the level of 3OHKyn is to use specific inhibitors for IDO. A recombinant human IDO was expressed to develop the inhibitors.
Takikawa
O
O
Australian Cataract Research Foundation, University of Wollongong, Australia. takikawa@uow.edu.au
Littlejohn
T
T
Jamie
J F
JF
Walker
M J
MJ
Truscott
R J
RJ
D000368:Aged; D002386:Cataract / Q000209:etiology / Q000503:physiopathology*; D002460:Cell Line; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma / Q000494:pharmacology; D007737:Kynurenine / Q000031:analogs & derivatives / Q000378:metabolism; D007908:Lens, Crystalline / Q000502:physiology* / Q000528:radiation effects*; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000201:enzymology; D011994:Recombinant Proteins / Q000378:metabolism; D014366:Tryptophan Oxygenase / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011994:Recombinant Proteins; C005045:3-hydroxykynurenine; D007737:Kynurenine; D007371:Interferon-gamma; D014366:Tryptophan Oxygenase