Aliphatic β-nitro alcohols for non-enzymatic collagen cross-linking of scleral tissue
Aliphatic β-nitro alcohols for non-enzymatic collagen cross-linking of scleral tissue
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DOI:
10.1016/j.exer.2008.06.008
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发表时间:
2008-09-01
影响因子:
3.4
通讯作者:
Trokel, Stephen L.
中科院分区:
文献类型:
--
作者:
Paik, David C.;Wen, Quan;Trokel, Stephen L.
The success of riboflavin photochemical cross-linking of the cornea in treating keratoconus and post-surgical keratectasia has prompted interest in cross-linking scleral tissue with a potential application to stabilize myopic progression. Applying an UVA light source to the sclera is difficult, particularly in the posterior region. An alternate pharmacologic approach to scleral cross-linking may be possible. The present study was undertaken in order to identify nitrite related compounds capable of inducing scleral tissue cross-linking and to gain information regarding the possible chemical mechanisms involved. 8 x 4 mm strips of porcine and human sclera were incubated in various concentrations of nitrite related agents (1-100 mM) at 37 degrees C. pH 7.4 was used for all experiments except those involving NaNO2. Following a 24-96 h incubation period, the samples were tested for cross-linking effects using thermal shrinkage temperature (T-S) analysis. Several compounds were studied including NaNO2, 2-nitroethanol, 2-nitro-1-propanol, 3-nitro-2-pentanol, 2-nitrophenol, 2-nitroethane, 2-aminoethanol, isopentyl nitrite, DPTA/NO, DETA/NO, and urea, a nitrous acid trap. The results indicate that short chain aliphatic beta-nitro alcohols (2-nitroethanol, 2-nitro-1-propanol, and 3-nitro-2-pentanol) are particularly effective cross-linking agents at pH 7.4, showing both time and concentration dependent effects. Furthermore, nitrosation does not appear to induce tissue cross-linking. In conclusion, aliphatic beta-nitro alcohols can cross-link scleral tissue at physiologic pH and temperature. Since beta-nitro alcohols are known to have reasonable toxicity profiles, these agents could find utility as pharmacologic cross-linking agents for scleral thinning disease. (C) 2008 Elsevier Ltd. All rights reserved.