Glucose-induced cataract in CuZn-SOD null lenses: an effect of nitric oxide?
Lenses from mice lacking the antioxidant enzyme copper-zinc superoxide dismutase (SOD1) show elevated levels of superoxide radicals and are prone to developing cataract when exposed to high levels of glucose in vitro. As superoxide may react further with nitric oxide, generating cytotoxic reactive nitrogen species, we attempted to evaluate the involvement of nitric oxide in glucose-induced cataract. Lenses from SOD1-null and wild-type mice were incubated with high or normal levels of glucose (55.6 and 5.56 mM). A nitric oxide synthase inhibitor (L-NAME) or a nitric oxide donor (DETA/NO) was added to the culture medium. Cataract development was assessed using digital image analysis of lens photographs and cell damage by analyzing the leakage of lactate dehydrogenase. The levels of superoxide radicals in the lenses were also measured. L-NAME was found to reduce cataract development and cell damage in the SOD1-null lenses exposed to high glucose. On the other hand, DETA/NO accelerated cataract development, especially in the SOD1-null lenses. These lenses also showed a higher leakage of lactate dehydrogenase than wild-type controls. We conclude that a combination of high glucose and absence of SOD1 increases the formation of cataract and that nitric oxide probably contributes to this process.
Olofsson
Eva M
EM
Department of Clinical Sciences/Ophthalmology, Umeå University, SE-901 87 Umeå, Sweden. eva.olofsson@ophthal.umu.se
Marklund
Stefan L
SL
Behndig
Anders
A
D000818:Animals; D002386:Cataract / Q000139:chemically induced*; D003470:Culture Media; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000009:adverse effects*; D007908:Lens, Crystalline / Q000378:metabolism / Q000473:pathology*; D049449:Luminescence; D051379:Mice; D018345:Mice, Knockout; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D003470:Culture Media; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D005947:Glucose; D019331:NG-Nitroarginine Methyl Ester