Determination of aldose reductase activity in the eye by localized magnetic resonance spectroscopy.
The polyol pathway plays an important role in the formation of diabetic complications of the eye. Due to variations in the pharmacokinetic properties of aldose reductase inhibitors and variations in the degradation of the blood-ocular barrier, it is often difficult to determine the proper intraocular levels of aldose reductase inhibitor required for inhibition of aldose reductase activity in ocular tissues. Utilizing localized magnetic resonance spectroscopy (MRS), the present method can determine adequate inhibition of aldose reductase activity in the lens by noninvasively measuring polyol pathway activity in the eye. New Zealand White rabbits, under anesthesia, were administered an intravitreal injection of 3-fluoro-3-deoxy-D-glucose (3FDG). Localized MRS was then used to assess polyol pathway activity by determining the levels of 3-fluoro-3-deoxy-D-sorbitol (3FS) and 3-fluoro-3-deoxy-D-fructose (3FF) metabolite formation from 3FDG in the eye. MRS was able to follow the loss of 3FDG from the vitreous into the anterior segment of the eye and particularly into the lens and aqueous. The primary metabolism of 3FDG observed by MRS was the formation of 3FS in the lens that is catalyzed by aldose reductase. Production of 3FS was linear in time and decreased with the oral administration of an aldose reductase inhibitor.
Lizak
M J
MJ
NIH MRI Research Facility, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA. LizakM@ninds.nih.gov
Mori
K
K
Kador
P F
PF
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D003847:Deoxyglucose / Q000031:analogs & derivatives*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005449:Fluorenes / Q000494:pharmacology; D006827:Hydantoins / Q000494:pharmacology; D007908:Lens, Crystalline / Q000201:enzymology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011817:Rabbits; D013012:Sorbitol / Q000378:metabolism
D004791:Enzyme Inhibitors; D005449:Fluorenes; D006827:Hydantoins; C052241:imirestat; C007253:3-deoxy-3-fluoro-D-glucose; D013012:Sorbitol; D003847:Deoxyglucose; D000449:Aldehyde Reductase