Mechanism of "hypoglycemic" cataract formation in the rat lens. I. The role of hexokinase instability.
Lenses from 100 gram albino rats remain clear and possess normal levels of Na+, K+, ATP, and hexokinase activity for 20 hours incubated in medium containing 12 mM glucose. Below 2.0 mM glucose, a cataract forms and there is an abrupt rise in lens Na+ and wet weight, a fall in lens K+, ATP, and hexokinase activity. The cataract is a thin lamellar opacity involving the anterior and posterior surfaces of the lens. If the lens is deprived of glucose for 48 hours, a nuclear cataract forms; the cortex between the superficial lamellar opacity and the nucleus being clear. This experimental cataract bears a striking resemblance to the hypoglycemic cataract seen in children. The thermal deactivation of hexokinase follows rapidly upon the depletion of its substrates (ATP and glucose) and is a primary factor leading to cataract formation. This was established by incubating the lens with 2-deoxyglucose, a competitive inhibitor of lens hexokinase. This compound blocks the entry of glucose into the glycolytic sequence. The cataract formed in its presence is identical morphologically and biochemically to that observed in a glucose-free medium. The effects of 2-deoxyglucose are prevented by increasing the glucose level; this rules out a direct toxic influence of 2-deoxyglucose and further supports the primary role of hexokinase thermolability in the etiology of this experimental cataract. This in vitro system appears to be an excellent experimental model for the study of the human hypoglycemic cataract.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002386:Cataract / Q000201:enzymology*; D003847:Deoxyglucose / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006593:Hexokinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007003:Hypoglycemia / Q000201:enzymology*; D066298:In Vitro Techniques; D007908:Lens, Crystalline / Q000201:enzymology*; D008297:Male; D011188:Potassium / Q000378:metabolism; D051381:Rats; D012964:Sodium / Q000378:metabolism; D013696:Temperature; D013997:Time Factors
D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D012964:Sodium; D006593:Hexokinase; D005947:Glucose; D011188:Potassium