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David C. Paik, Quan Wen; Aliphatic β-nitroalcohols For Therapeutic Tissue Cross-linking: In Vitro Efficacy Studies Using Higher Order Nitroalcohols. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5212.
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The ability to selectively enhance the biomechanical properties of a given tissue in vivo could have widespread clinical utility. Our recent studies suggest that aliphatic β-nitro alcohols (BNAs) may represent a useful class of compounds for use as in vivo therapeutic corneoscleral cross-linking agents. In addition, higher order nitroalcohols (HONAs), have greater efficacy than their mono-nitroalcohol counterparts. Thus, the current study was undertaken in order to explore the extent to which increased efficacy is possible with HONAs over mono-nitroalcohols.
10 x 4mm scleral strips were taken from fresh adult pig eyes and incubated in 1,3, and 10 mM concentrations of a mono-nitroalcohol (2-nitro-1-propanol = 2nprop), a nitro-diol (2-methyl-2-nitro-1,3-propanediol), and a nitro-triol (2-hydroxymethyl-2-nitro-1,3-propanediol) at pH 7.4, 37oC using methods previously described. Tissue cross-linking effects were evaluated after 1, 3, 5, 7, and 12 hours of reaction time using thermal shrinkage temperature (Ts) analysis also previously described.
The mono-nitroalcohol did not induce Ts shifts under the conditions studied. In contrast, both the nitro-diol and nitro-triol induced cross-linking effects in as little as 1hr. This was true for all the concentrations studied. Consistent with time and concentration dependent effects, the greatest Ts shifts were achieved using the highest concentration for the longest amount of time. Furthermore, Ts shifts comparable to riboflavin photochemical cross-linking were possible with as little as 1hr of exposure at 1mM concentration for both the nitro-diol and nitro-triol. The included figure is a summary of data for the nitro-diol.
HONAs are significantly more effective as tissue cross-linking agents than their mono-nitroalcohol counterparts. By comparison with our previous studies, the HONAs are at least 100 times more effective. Proof-of-concept experiments using live animals are in progress, the results of which will be reported in due course.
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