Combination of glycemic and oxidative stress in lens: implications in augmentation of cataract formation in diabetes.
It is well known that the incidence of cataract is higher in diabetics as compared to non-diabetics. Its rate of maturation is also faster in the diabetics. The precise mechanism of this acceleration is not clearly understood. It is hypothesized that this could be a result of the combination of the metabolic and oxidative stress induced by glycemia itself with the age-associated increase in ambient generation of oxyradical species. In the current studies, we have investigated this possibility using the galactose cataract model. Galactosemia was induced by feeding rats a 50% galactose diet. The increased susceptibility of the glycemic lenses to physiological damage by reactive oxygen species (ROS) was studied by incubating them in Tyrode in the absence and presence of menadione. The resulting physiological damage to the lens was assessed initially in terms of its ability to maintain Na+-K+ ATPase dependent active transport of potassium ions, as represented by the uptake of rubidium ions. Subsequently, the level of ATP, indexing the general metabolic status, and the level of glutathione (GSH), indexing the status of antioxidant reserve, were also determined. The uptake of rubidium in the normal lenses incubated in the presence of the quinone was depressed to more than 50% of the controls run in the basal medium. A similar depression existed in the galactosemic lenses in comparison to the normal lenses. However, in the presence of menadione, the inhibition of the uptake was accentuated further in the case of galactosemic lenses, the uptake here being only 20% of the normal controls. Similarly, the galactosemic lenses were also more susceptible to menadione dependent decrease in ATP and GSH.
Hegde
K R
KR
Department of Biochemistry, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Varma
S D
SD
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002386:Cataract / Q000209:etiology*; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications*; D007552:Isotonic Solutions; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000009:adverse effects; D012413:Rubidium / Q000378:metabolism; D024483:Vitamin K 3 / Q000494:pharmacology
D007552:Isotonic Solutions; D017382:Reactive Oxygen Species; C037692:Tyrode's solution; D024483:Vitamin K 3; D000255:Adenosine Triphosphate; D005978:Glutathione; D012413:Rubidium