Differential diagnosis of cataracts by crystallin subunit quantitation correlated with clinical and morphological observations
A large number of human cataractous lenses have been obtained for individual lens analysis. Classification and grouping of the lenses was initially based on the clinical description of both nuclear and cortical involvements made previous to surgical extraction. Measurements of the wet, dry and percentage dry weights were, in general, in agreement with those found in the literature and the relationship of these parameters to the stage of cataract is discussed. Iso- electric focussing of the water soluble (W.S.) and urea soluble (U.S.) fractions of the lenses yielded protein profile for each lens based on the levels of the individual polypeptide subunits as measured by densitometry. The profiles were found to reflect the nature of the lesion and, thus, the initial classification and grouping of the lenses was validated. Furthermore, comparisons made between the protein profiles of cataracts of similar morphopathology but differing aetiology - those considered here include diabetes, retinitis pigmentosa and leprosy - showed that the protein profile reflected not only the location and stage of the lesion within the lens but also the mechanism of cataractogenesis.Computer analysis of information collected from a population of cataract patients and controls, concerning their social and medical backgrounds as well as their ophthalmic record and clinical chemistry record of blood plasma constituents, was carried out. A number of single variables were found to be associated with cataract incidence. They included the medical conditions; diabetes, cardiovascular disease, high blood pressure and other eye diseases; and the prolonged use of some drugs including the tranquilisers, barbiturates, MAOI, tricyclics and phenothiazines, and steroids and miotics when applied topically to the eye. High levels of the plasma constituents urea and glucose and low levels of calcium, cholesterol, total protein, albumin, total CO2, phosphate, alanine aminotransferase and asparagine aminotrans- ferase are also found to associate with cataract incidence. A lower incidence of cataract is observed in individuals who had suffered from serious infective bacterial illness and those treated with antibacterial drugs. A lower incidence was also observed in individuals who were not total abstainers from alcohol.Some preliminary combinatorial analysis has shown the synergism of two risk factors, high levels of plasma urea and plasma fasting glucose and the varying counteractivity of high and low risk factors when combined.The future role of epidemiological studies combined with biochemical studies to elucidate the mechanisms of cataractogenesis and to allow the identification of individuals who are particularly at risk with the aim of being able to take preventive measures is discussed.