Abstract
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-γ. Immuno-suppressants which inhibit production of IFN-γ 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.
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References
Abi-Hanna, D., McCluskey, P., and Wakefieldl, D., 1989, HLA antigens in the iris and aqueous humor gamma interferon levels in anterior uveitis, Invest. Ophthalmol. Vis. Sci. 30:990–994.
Aquilina, J.A., Carver, J.A., and Truscott, R.J.W., 1997, Oxidation of products of 3-hydroxykynurenine bind to lens proteins: Relevance for nuclear cataract, Exp. Eye Res. 64:727–735.
Bando, M., Nakajima, A., and Satoh, K., 1981, Spectrophotometric estimation of 3-OH L-kynurenine O-β-glucoside in the human lens, J. Biochem. (Tokyo) 89:103–109.
Fu, S., Dean, R., Southan, M., and Truscott, R.J.W., 1998, The hydroxyl radical in lens nuclear cataractogenesis, J. Biol. Chem. in press.
Garner, M.H. and Sepector, A., 1980, Selective oxidation of cysteine and methionine in normal and senile cataractous lenses. Proc. Natl. Aead. Sci. USA 77:1274–1277.
Kupfer, C., Underwood, B., and Gillen, T., 1994, Leading causes of visual impairment world wide, in: Principles and Practice of Ophthalmology Basic Science, (D.M., Albert, and F.A., Jakobiec, eds), pp. 1249–1255, W.B. Saunders Co., Philadelphia.
Peterson, A.C., La Loggia, A.J., Hamaker, L.K., Arend, R.A., Fisette, P.L., Ozaki, Y., Will, J.A., Brown, R.R., and Cook, J.M., 1993, Evaluation of substituted β-carbolines as noncompetitive indoleamine 2,3-dioxy-genase inhibitors, Med. Chem. Res. 3:473–482.
Southan, M.D., Truscott, R.J.W., Jamie, J.F., Pelosi, L., Walker, M.J., Maeda, H., Iwamoto, Y., and Tone, S., 1996, Structural requirement of the competitive binding of recombinant human indoleamine 2,3-dioxygenase, Med. Chem. Res. 6:343–352.
Spector, A., 1995, Oxidative stress-induced cataract: mechanism of action, FASEB J. 9:1173–1182.
Sweeney, M.H.J. and Truscott, R.J.W., 1998, An impediment to glutathione diffusion in older normal human lenses: a possible precondition for nuclear cataract, Curr.Eye Res. in press.
Takikawa, O., Kuroiwa, T, Yamazaki, F., and Kido, R., 1988, Mechanism of IFN-γ action: characterization of indoleamine 2,3-dioxygenase in various human cells induced by IFN-γ and evaluation of the enzyme-mediated tryptophan degradation in its anticellular activity, J. Biol. Chem. 263:2041–2048.
Tone, S., Takikawa, O., Habara-Ohkubo, A., Kadoya, A., Yoshida, R, and Kido, R., 1990, Primary structure of human indoleamine 2,3-dioxygenase deduced from the nucleotide sequence of its cDNA, Nucleic Acids Res. 18:367.
Truscott, R.J.W. and Augusteyn, R.C., 1977, The state of sulphydryl groups in normal and cataractous human lenses, Exp. Eye. Res. 25:139–148.
Truscott, R.J.W, Wood, A.M., Carver, J.A., Sheil, M.M., Stutchbury, G.M., Zhu, J., and Kilby, G.W., 1994, A new UV-filter compound in human lens, FEBS Letters. 348:173–176.
Vasquez, S. and Truscott, R.J.W, 1998, Oxidation of 3-hydroxy kynurenine. In: Abstracts of 13th International Congress of Eye Research, p.141.
van Heyningen, R., 1971, Fluorescent glucoside in the human lens, Nature, 203:411–417.
Wood, A.M. and Truscott, R.J.W, 1993, UV filters in human lenses: Tryptophan catabolism, Exp. Eye Res. 56:317–325.
Wood, A.M. and Truscott, R.J.W., 1994, Ultraviolet filter compounds in human lenses: 3-hydroxykynurenine glucoside formation, Vision Res. 34:1369–1374.
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Takikawa, O., Littlejohn, T., Jamie, J.F., Walker, M.J., Truscott, R.J.W. (1999). Regulation of Indoleamine 2,3-Dioxygenase, The First Enzyme in Uv Filter Biosynthesis in the Human Lens. In: Huether, G., Kochen, W., Simat, T.J., Steinhart, H. (eds) Tryptophan, Serotonin, and Melatonin. Advances in Experimental Medicine and Biology, vol 467. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4709-9_31
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DOI: https://doi.org/10.1007/978-1-4615-4709-9_31
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