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首页> 外文期刊>Investigative ophthalmology & visual science >Mechanisms of Corneal Tissue Cross-linking in Response to Treatment with Topical Riboflavin and Long-Wavelength Ultraviolet Radiation (UVA)
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Mechanisms of Corneal Tissue Cross-linking in Response to Treatment with Topical Riboflavin and Long-Wavelength Ultraviolet Radiation (UVA)

机译：局部核黄素和长波紫外线（UVA）治疗对角膜组织交联的作用机制

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Purpose.: Treatment of de-epithelialized human corneas with riboflavin (RF) + long-wavelength ultraviolet light (UVA; RFUVA) increases corneal stroma tensile strength significantly. RFUVA treatment retards the progression of keratoconus, perhaps by cross-linking of collagen molecules, but exact molecular mechanisms remain unknown. Research described here tested possible chemical mechanisms of cross-linking. Methods.: Corneas of rabbits and spiny dogfish sharks were de-epithelialized mechanically, subjected to various chemical pretreatments, exposed to RFUVA, and then subjected to destructive tensile stress measurements. Tensile strength was quantified with a digital force gauge to measure degree of tissue cross-linking. Results.: For both rabbit and shark corneas, RFUVA treatment causes significant cross-linking by mechanism(s) that can be blocked by the presence of sodium azide. Conversely, such cross-linking is greatly enhanced in the presence of deuterium oxide (D2O), even when RF is present at only one tenth the currently used clinical concentrations. Blocking carbonyl groups preexisting in the stroma with 2,4-dinitrophenylhydrazide or hydroxylamine blocks essentially all corneal cross-linking. In contrast, blocking free amine groups preexisting in the stroma with acetic anhydride or ethyl acetimidate does not affect RFUVA corneal cross-linking. When both carbonyl groups are blocked and singlet oxygen is quenched, no RFUVA cross-linking occurs, indicating the absence of other cross-linking mechanisms. Conclusions.: RFUVA catalyzes cross-linking reactions that require production of singlet oxygen (1O2), whose half-life is extended by D2O. Carbonyl-based cross-linking reactions dominate in the corneal stroma, but other possible reaction schemes are proposed. The use of D2O as solution media for RF would enable concentration decreases or significant strength enhancement in treated corneas.
机译：目的：用核黄素（RF）+长波紫外线（UVA; RFUVA）治疗去上皮的人角膜，可显着增加角膜基质的抗张强度。 RFUVA治疗可能通过胶原分子的交联来延迟圆锥角膜的进展，但是确切的分子机制仍然未知。这里描述的研究测试了可能的交联化学机理。方法：将兔和多角鲨鲨的角膜进行机械上皮除臭，进行各种化学预处理，使其暴露于RFUVA，然后进行破坏性拉伸应力测量。用数字测力计量化拉伸强度，以测量组织交联的程度。结果：对于兔角膜和鲨鱼角膜，RFUVA治疗均会通过叠氮化钠的存在而被阻断，从而引起显着的交联。相反，即使当RF仅以当前使用的临床浓度的十分之一存在时，在氘化氢（D2O）的存在下，这种交联也会大大增强。用2，4-二硝基苯酰肼或羟胺封闭基质中预先存在的羰基基团基本上可阻断所有角膜交联。相反，用乙酸酐或乙酰亚胺酸乙酯封闭基质中预先存在的游离胺基不会影响RFUVA角膜交联。当两个羰基均被封闭且单线态氧被淬灭时，不会发生RFUVA交联，表明不存在其他交联机理。结论：RFUVA催化需要生成单线态氧（1O2）的交联反应，单线态氧的半衰期可通过D2O延长。基于羰基的交联反应在角膜基质中占主导地位，但提出了其他可能的反应方案。将D2O用作RF的溶液介质将使治疗的角膜浓度降低或强度显着提高。

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