Studies on some post-translational modifications of lens crystallins

Abstract

The eye lens is a highly refracting and transparennissue that focuses light to form newlineimages on the retina. The state of transparency of the lens is thus of utmost importance in newlinedetermining the ability of an organism to visualize things. The vertebrate lens contains newlinehigh concentrations of structural proteins called the crystallins, packed densely in newlineenucleated lens fibre cells in a spatial organization that reduces light scatter. The newlinecondition in which the lens loses its transparency and becomes colored and opaque is newlinetermed cataract. Cataract is a major cause of visual impairment throughout the world. newlineCataract is characterized by the presence of ( 1) high concentrations of newlinechromophores that absorb in the ultraviolet A and visible range, (2) large particles that newlinecontain covalently and noncovalently aggregated proteins leading to increased light newlinescatter. Besides these, there are alterations in protein conformations, intermolecular newlineinteractions and the organization of proteins and also the lens fibre cells, leading to newlinechanges in the refractive index of the lens. These manifestations in most cases are a result newlineof accumulated protein modifications (post-translational non-enzymatic or oxidative in newlinenature) brought about by a variety of factors including environmental stress (e.g., newlineexposure to strong sunlight as in the tropics), behavioural habits (e.g., smoking), diseased newlineconditions (e.g., diabetes or diarrhoea) as well as the normal process of aging itself. newlineOxidative modifications themselves result from the photosensitized or metabolic newlinegeneration of reactive oxygen species and also because of a compromise in the newlineendogenous antioxidant protection mechanisms. Various changes seen in the crystallins newlineupon in vitro oxidative studies mimic the state of these proteins seen in vivo during newlinecataract or aging. The effects of these modifications are felt acutely by the long-lived newlinecrystallins, due to the sluggish protein turnover in the lens.