Metabolic Changes in Rabbit Lens Induced by Treatment with Dexamethasone

Abstract

Metabolic changes in the rabbit lens have been studied by means of nuclear magnetic resonance spectroscopy. These changes have been induced by prolonged topical treatment with dexamethasone. Our results demonstrate an increase in sorbitol, sorbitol-3-phosphate, fructose-3-phosphate, glycerol-3-phosphate and glucose-6-phosphate levels and a decrease in glutathione sulphate (GSH) and myo-inositol levels, in agreement with what was observed in lenses from streptozocin-diabetic rats before lens opacity. The hyperglycaemia can only partially explain all these observed biochemical variations. The lack of increase in the intermediates of pentose cycle, such as sedoheptulose-7-phosphate, seems to support the hypothesis of an inhibition of glucose-6-phosphate dehydrogenase by dexamethasone treatment. Finally dexamethasone treatment induces a decrease in GSH. The decreasing or the loss of GSH has been suggested as a possible pathogenic mechanism in the cataract formation.

Vehicle of triamcinolone acetonide is associated with retinal toxicity and transient increase of lens density

“…Steroid-induced cataract is considered to be associated with oxidative damage and the existence of steroid receptors located in the lens [23,30,37]. In our study, intravitreal TA can cause a rapid transient increase of lens density in group 4, which is associated with vehicle of TA.…”

High-resolution magic angle spinning 1H NMR spectroscopy of metabolic changes in rabbit lens after treatment with dexamethasone combined with UVB exposure

“…Concomitantly, the concentration of lactate decreased reaching a level similar to that measured after UVB exposure only. In contrast, Pescosolido et al [33] did not find any change in lenticular lactate concentration after long-term dexamethasone treatment of rabbit eyes. This implies that the decreased lactate concentration in our study may have been caused by the UVB irradiation.…”

“…Metabolic changes in the rabbit lens after treatment with steroids like dexamethasone have previously been investigated by NMR spectroscopy, i.e. organophosphate profiling of incubated lenses and their extracts [12] and analysis of lens extracts after long-term topical treatment [33]. In our laboratory, 19 F and 1 H NMR spectroscopy have been applied to monitor penetration of dexamethasone into the anterior segment of the eye after short-term topical treatment, analysing tissue extracts from cornea and lens [29].…”

N-acetylcysteine amide protects against dexamethasone-induced cataract related changes in cultured rat lenses

“…The decreased activity of GR seen in our experiments with Dex treatment supports our hypothesis of GSH depletion upon treatment with Dex. A decrease in the lenticular GSH levels has been observed upon treatment with glucocorticoids [13,35,63]. In vivo treatment of rabbits with the Dex eye drops, as used for cataract surgery, reduced GSH levels in the lens [63].…”

“…A decrease in the lenticular GSH levels has been observed upon treatment with glucocorticoids [13,35,63]. In vivo treatment of rabbits with the Dex eye drops, as used for cataract surgery, reduced GSH levels in the lens [63]. In addition, free radical scavengers have also been reported to prevent GC-induced cataract formation [64][65][66] by increasing GSH levels and decreasing LPO.…”