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R. Phillip Eaton, MD; William Sibbett, MD; Alice Harsh, RN
University of New Mexico School of Medicine Albuquerque

JAMA. 1985;254(11):1452-1453.

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In Reply.—

The concerns of Dr Frank that the enzyme aldose reductase may be intracellular and thus unavailable to produce sugar alcohols for collagen incorporation are appropriate. Since the 1959 investigation of Van Heyningen et al¹ with dialyzed extracts of rat lens, all studies of this enzyme have used total tissue extracts with no attempt to distinguish between intracellular and extracellular enzyme. Thus, the actual tissue location of aldose reductase is not established.

In fact, the actual issue is not the location of the enzyme aldose reductase, but in what site the polyol accumulates, independent of its site of generation. Microscopic examination of nerves from galactose-fed rats and streptozotocin-treated diabetic rats has demonstrated accumulation of water in the endoneurial space surrounding the axon, while the axon actually appears to shrink in diameter.^2,3 It has even been suggested that chronic hyperosmolality of endoneurium interstitial fluid could produce axon shrinkage . . . [Full Text PDF of this Article]

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