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Topical Uptake of Guanidino Compound NC1 and N-Acetyl-Cysteine Into Rabbit and hSVCT2 Mouse Lens for the Prevention of Senile Cataracts

Senile cataracts are strongly associated with postsynthetic modifications of lens crystallins by advanced ascorbylation end products that are known to enhance crystallin aggregation and light scattering. Guanidino compound NC1 fed to hSVCT2 mice was previously found to block ascorbylation reactions (Fan et al, IOVS 49:4945-52, 2008). As a preamble to the topical application of NC1 as a drug applied to the human eye, we have compared the uptake of NC1 and N-acetyl-cysteine (NAC) in rabbit lens in vitro and in vivo, as well as the ability of NC1 to block ascorbylation when applied topically to hSVCT2 mouse model of lenticular aging. Guanidino compound NC1 is readily taken up via topical application to the lens, in contrast to NAC which suppressed only fluorescence. This, with the broad ability of NC1 to inhibit undesirable crystallin modifications, opens up the possibility of testing the anticataract potential of NC1 in clinical trial.

Cataracts; Lens Crystallins; Aggregation

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