Levels of Reduced Pyridine Nucleotides and Lens Photodamage

Abstract

Since most of the known factors that are associated with cataract formation are oxidative in nature, one would expect that a highly reductive environment might arrest or retard the progress of cataract formation. Reduced nucleotides, both NADH and NADPH, are potent reductants with a large negative redox potential of -320 mV. Lenses of certain species contain high levels of these nucleotides, presumably due to the presence of taxon specific crystallins. We have utilized this situation to investigate whether the levels of reduced pyridine nucleotides modulate photo-oxidative damage to the lens. We have monitored the time dependent loss of tryptophan fluorescence upon photodamage for lenses from guinea pig, rabbit and frog (Rana) that contain high levels of pyridine nucleotides and compared with the lenses from rat, Xenopus and a mutant strain of guinea pig that contain significantly lower amounts of these nucleotides. About 75% and 90% of the initial fluorescence intensity is lost in the case of rat and Xenopus lenses, respectively, after a total of 35 min exposure. Rabbit, guinea pig and frog lenses, under identical conditions, show only about 35-40% loss of the initial fluorescence. It appears that the lenses that contain high levels of reduced nucleotides are less susceptible to photodamage. The observed anti-oxidative role of reduced nucleotides in the lenses indicates the possibility of testing reductants (NADPH, NADH and their functional analogues) as potential candidates to therapeutically intervene in the process of cataractogenesis.

A Retinaldehyde Dehydrogenase as a Structural Protein in a Mammalian Eye Lens

“…Other benefits may have been protection against the toxic effects of aldehydes resulting from light-induced oxidation of lens components, or generalized anti-oxidant and UV-filtering effects though sequestration of NAD(H) or retinoids in the lens (1,28,43,44).…”

Oxidative Stress, Lens Gap Junctions, and Cataracts

“…However, the lens contains several nonenzymatic and enzymatic mechanisms to protect itself from oxidative stress and to repair oxidatively damaged cell components. The nonenzymatic mechanisms include the presence of high concentrations of ascorbate, reduced glutathione (GSH), crystallins (which act as protein chaperones), and free UV filters (e.g., tryptophan derivatives in the human lens and NAD(P)H in rabbit, guinea pig and frog lenses (2,16,125,127).…”

Evolution of the Aldose Reductase-Related Gecko Eye Lens Protein ρB-Crystallin: A Sheep in Wolf's Clothing

“…L. lugubris is active primarily in the dark and, thus, is not exposed to intense solar radiation. This makes it questionable whether the presence of B-crystallin has any selective advantage for the animal in protecting against radiation damage, as proposed for other nucleotide cofactor-binding enzymecrystallins (Rao and Zigler 1992;Wistow et al 1987). For the time being, it thus remains elusive whether Bcrystallin originated as a selectively advantageous character or rather by neutral evolutionary processes, allowing it to be maintained as long as the protein is compatible with proper lens functioning.…”

“…Such a change in lifestyle would favor the recruitment in the lens of protective mechanisms against the damage of solar radiation. It has indeed been suggested that the pyridine nucleotides associated with many enzyme-crytallins protect against the deleterious effects of, especially, near-UV light (Wistow et al 1987) or as a defense against oxidative stress (Rao and Zigler 1992).…”