Calcium and the physiology of cataract

Abstract

Calcium has long been known to play a role in cataract formation but techniques have only recently become available for investigating the physiological mechanisms. Previous studies showed that lens membrane permeability alters when the external calcium concentration falls below 1 mM, so it was interesting that values for human aqueous from cataract patients ranged from 0.45 to 2.0 mM. The mean value for the aqueous was one half that for the plasma. The calcium concentration in cataractous lenses ranged from 0.1 to 64 mM and lenses with a high calcium concentration also had a high sodium content. In lenses with near normal sodium content the highest calcium concentrations were associated with highly localized opacities, while nuclear cataracts had a low calcium content. The relationship between calcium and transparency was investigated in a rat lens system using ion-sensitive microelectrodes. The distribution of free calcium in the lens varied with age and was correlated with a change in the sensitivity of the lens to cold cataract and a change in lens birefringence. The highest free calcium levels were obtained from lenses incubated in 10 mM-calcium in the absence of glucose and these lenses showed most light scattering. Ion-sensitive microelectrode techniques applied to human lenses yielded calcium levels of 0.1 microM-2 mM. In lenses with dense, highly localized opacities the calcium distribution was not uniform and was highest in regions that scattered most light. The movement of calcium through individual membrane channels was investigated using patch clamp techniques. Three types of ionic channels have been identified in the lens. The smallest appears to be a calcium channel; the larger current fluctuations are associated with sodium and potassium movements. In organ culture studies of the bovine lens, a marked decrease in protein synthesis and net leakage of proteins was associated more strongly with an increase in calcium than with an increase in sodium. The stability of the lens protein gel thus seems to depend on maintaining a low internal level of calcium ions.