Biochemical blood parameters in people with a normal crystalline lens and in cataracts]

The activity of Na+,K+ATPase, gamma-glutamyltranspeptidase, ceruloplasmin, total antioxidative activity of water-soluble antioxidants, the contents of vitamins C and E, free amino-nitrogen and peroxide resistance of erythrocytes were determined at the blood's plasma of healthy persons (120 persons) and suffered from aged cataract (437 persons) of three aged groups (up to 40 years, 40-60 years and elder then 60 years). We have shown, that changes, which has been connected with cataractogenesis and age dependent changes are not equal. The lowering of activity of Na+,K(+)-ATPase, gamma-glutamyltranspeptidase and level of vitamin E was expressed less during the ageing, then during the development of lenses opacification. The increase of activity of oxidase during the cataractogenesis is less significant, then age depended inhibition of this enzyme. The opposite tendency (the lowering of activity at the patients with cataract is more expressed, then compensatory activations of these parameters at the persons of the corresponding age with transparent lenses) was revealed for total antioxidative activity of water-soluble antioxidants.     

Change in potassium ion homeostasis of the crystalline lens in mice with hereditary cataracts (the CatFr line)

Fraeser mouse lens morphology and potassium homeostasis were studied. It was shown that just at the age of one month mouse lens exposed "bull" cells which could be observed in patients with senile cataract as well. Nucleated fusiform extended cells were found 4 months later in the central part of the lens which was not typical for this part of the whole normal lens. Studied homogenates of 34 mice with hereditary cataract demonstrated statistically significant increase (1.5-fold about) in K+-content estimated for the whole lens weight as compared to the control group (38 lens). The difference in potassium content in aqueous humor between affected and control animals was statistically indistinguishable. The role of potassium ions in Fraeser cataract pathogenesis is discussed.     

Peroxide-metabolizing systems of the crystalline lens

The ability of transparent and cataractous human, rabbit and mice lenses to metabolize hydrogen peroxide in the surrounding medium was evaluated. Using a chemiluminescence method in a system of luminol-horseradish peroxidase and a photometric technique, the temperature-dependent kinetics of H₂O₂ decomposition by lenses were measured. The ability of opaque human lenses to catalyze the decomposition of 10^?4 M H₂O₂ was significantly decreased. However, this was reserved by the addition of GSH to the incubation medium. Incubation of the mice lenses with the initial concentration H₂O₂ 10^?4 M led to partial depletion of GSH in normal and cataractous lenses. Human cataractous lenses showed decreased activities of glutathione reductase, glutathione peroxidase (catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids), superoxide dismutase, but no signs of depletion in activities of catalase or glutathione peroxidase (utilizing H₂O₂). The findings indicated an impairment in peroxide metabolism of the mature cataractous lenses compared to normal lenses to be resulted from a deficiency of GSH. An oxidative stress induced by accumulation of lipid peroxidation products in the lens membranes during cataract progression could be considered as a primary cause of GSH deficiency and disturbance of the redox balance in the lens.     

Connections between connexins, calcium, and cataracts in the lens

There is a good deal of evidence that the lens generates an internal micro circulatory system, which brings metabolites, like glucose, and antioxidants, like ascorbate, into the lens along the extracellular spaces between cells. Calcium also ought to be carried into the lens by this system. If so, the only path for Ca2+ to get out of the lens is to move down its electrochemical gradient into fiber cells, and then move by electrodiffusion from cell to cell through gap junctions to surface cells, where Ca-ATPase activity and Na/Ca exchange can transport it back into the aqueous or vitreous humors. The purpose of the present study was to test this calcium circulation hypothesis by studying calcium homeostasis in connexin (Cx46) knockout and (Cx46 for Cx50) knockin mouse lenses, which have different degrees of gap junction coupling. To measure intracellular calcium, FURA2 was injected into fiber cells, and the gradient in calcium concentration from center to surface was mapped in each type of lens. In wild-type lenses the coupling conductance of the mature fibers was approximately 0.5 S/cm2 of cell to cell contact, and the best fit to the calcium concentration data varied from 700 nM in the center to 300 nM at the surface. In the knockin lenses, the coupling conductance was approximately 1.0 S/cm2 and calcium varied from approximately 500 nM at the center to 300 nM at the surface. Thus, when the coupling conductance doubled, the concentration gradient halved, as predicted by the model. In knockout lenses, the coupling conductance was zero, hence the efflux path was knocked out and calcium accumulated to approximately 2 microM in central fibers. Knockout lenses also had a dense central cataract that extended from the center to about half the radius. Others have previously shown that this cataract involves activation of a calcium-dependent protease, Lp82. We can now expand on this finding to provide a hypothesis on each step that leads to cataract formation: knockout of Cx46 causes loss of coupling of mature fiber cells; the efflux path for calcium is therefore blocked; calcium accumulates in the central cells; at concentrations above approximately 1 microM (from the center to about half way out of a 3-wk-old lens) Lp82 is activated; Lp82 cleaves cytoplasmic proteins (crystallins) in central cells; and the cleaved proteins aggregate and scatter light.     

Analysis of human crystalline lens accommodation

The behavior of the human crystalline lens during accommodation is analytically studied. The lens is modeled as a closed axisymmetrical membrane shell of varying thickness enclosing an incompressible liquid. To simulate zonular tension associated with lenticular accommodation, an axisymmetrical radial force or displacement is imposed around the shell equator. Two second-order, simultaneous, nonlinear governing differential equations are derived. Numerical results, obtained from the investigation of human lens profiles of three independently published MRI images and a drawing of a microphotograph, demonstrate that when zonular traction within the physiological force range of the ciliary muscle is exerted, both central lens thickness and central optical power increase. Qualitatively, these increases are independent of lens shape. However, the magnitude of these changes is dependent on the initial profile of the lens and is enhanced by the "natural" variation in capsular thickness. Only when a pulling force significantly exceeds the force capacity of the ciliary muscle does the lens flatten and its central thickness and optical power decrease.