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J. C. Lim, T. Sherwin, P. J. Donaldson; Cystine/Glutamate Exchanger (xC-) Expression in the Human Lens: A Role in the Initiation of Age Related Nuclear Cataract?. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2280. doi: https://doi.org/.
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We have identified in the rat lens the cystine/glutamate exchanger XC- as a potential pathway to specifically enhance the levels of the low molecular mass antioxidant cysteine in the lens core-the area affected by age related nuclear (ARN) cataract1,2. Here we have translated our initial findings from rat to human lenses to determine whether Xc- is also expressed in the human lens.
Human lenses were obtained from organ donors sourced through the New Zealand National Eye bank. RT-PCR was used to produce a profile of XC- transcript expression. Western blotting was utilized to determine protein expression levels in the outer cortex, inner cortex and core regions. Immunocytochemistry was used to further localise Xc- expression patterns.
A panel of donor lenses were screened and XC- was shown to be expressed at both the transcript and protein level. In a 36 year old human lens, XC- was expressed in all regions of the lens. In contrast, in a 76 year old human lens, Xc- was only detected in the outer cortex and was absent from the inner cortex and core. Immunocytochemistry showed XC- to be specifically localised to the outer cortex region of a 72 year old lens confirming the restricted localisation of XC- in older human lenses.
Our results show XC- is expressed in the human lens and its expression pattern changes with increasing age. This suggests that in the nucleus of older lenses, XC- may be modified and rendered incapable of accumulating cyst(e)ine in the lens nucleus. Since cysteine has been proposed to act as a low molecular weight antioxidant3, dysfunction of Xc- would expose the nucleus to oxidative damage and increase the risk of ARN cataract.References:1 Lim, J., Lam, Y.C., Kistler, J and Donaldson, P.J. Invest Ophthalmol Vis Sci 2005 46(8): 2869-77.2 Li, L., Lim, J., Jacobs, MD., Kistler J and Donaldson, PJ. Invest Ophthalmol Vis Sci 2006 48(3):1253-60.3Lou, M.F. Prog Retin Eye Res. 2003 22(5):657-82. Review
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