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M. H. Gangadhariah, S. Padmanabha, L. Reneker, R. H. Nagaraj; Glyoxalase I Overexpression Inhibits AGE Formation in the Lens. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2132.
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Glyoxalase I together with glyoxalase II metabolizes a variety of -dicarbonyl compounds including methylglyoxal (MGO). -Dicarbonyl compounds react with arginine and lysine residues in lens proteins to form advanced glycation end products (AGEs). The purpose of this study is to determine the role of glyoxalase I in controlling AGE formation in the lens.
A transgenic mouse line was developed that expressed human glyoxalase I in the lens. Lenses from transgenic (Tg) and wild type (Wt) animals (2-3 months old) were organ cultured in the presence or absence of 5 mM DL-glyceraldehyde (GLD) (a precursor of MGO), 5 mM ascorbate or 5 mM ribose for 48 hrs (osmolality=300 mOsm). Glyoxalase I, GSH, MGO and AGEs were measured by either spectrophotometry, HPLC or ELISA.
Tg lenses were similar in size and morphology to Wt lenses up to 6-months of age. Glyoxalase I was highly overexpressed in the epithelium and outer cortex in transgenic animals, the enzyme activity was 7 times higher in Tg lenses relative to Wt lenses. Glyoxalase I overexpression did not cause any change in GSH content but the glyoxalase I activity in Tg lenses decreased upon incubation with GLD, ribose or ascorbate. Glyoxalase I overexpression decreased the content of argpyrimidine and hydroimidazolone (see Table below). Pentosidine content increased in ascorbate and ribose incubated Wt lenses and further increased in ribose incubated Tg lenses, but decreased in ascorbate incubated Tg lenses.
Our results show that glyoxalase I overexpression significantly reduces AGE formation from MGO and ascorbate, but promotes pentosidine synthesis from ribose in lens proteins.
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