Chemical Cross-Linking of Corneal Tissue to Reduce Progression of Loss of Sight in Patients With Keratoconus.
Chemical Cross-Linking of Corneal Tissue to Reduce Progression of Loss of Sight in Patients With Keratoconus.
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DOI：
10.1167/tvst.10.5.6
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发表时间：
2021-04-29
影响因子：
3
通讯作者：
Williams R
中科院分区：
文献类型：
--
作者：
Haneef A;Giridhara Gopalan RO;Rajendran DT;Nunes J;Kuppamuthu D;Radhakrishnan N;Young TH;Hsieh HY;Prajna NV;Willoughby CE;Williams R
我们的目的是开发一种新的化学交联剂治疗圆锥角膜的反应，二羧酸间隔分子和胺功能基团的蛋白质结构的组织使用N-酰亚胺化学。我们建议将其作为圆锥角膜常规交联治疗的替代方案。该研究涉及交联剂配方的优化。测量应用交联剂后离体猪和人角膜的机械刚度。进行组织化学分析，以记录交联剂处理离体猪和人以及体内兔角膜后的总体形态变化。末端脱氧核苷酸转移酶介导的dUTP-X缺口末端标记（TUNEL）染色，以研究交联剂的凋亡作用。通过研究处理后猪和人角膜的细胞生长外植体培养物和免疫染色试验，评价交联剂的细胞毒性潜力。我们在不去除角膜上皮的情况下使用猪和人角膜进行的离体实验中证明了临床相关的硬度增加。组织学分析显示角膜的大体形态没有变化，也没有细胞凋亡的证据。兔眼的体内治疗显示角膜上皮最初变薄，7天后恢复，尽管细胞具有异常的规律性。治疗后角膜外植体培养物的细胞生长进一步证实了治疗后的细胞存活。角膜组织的这种化学交联具有优于当前治疗选择的潜在优势，包括比紫外线A治疗对基质细胞的细胞毒性更低。该交联剂有可能成为圆锥角膜的治疗方法，因为它克服了使用专门设备进行手术的需要，并确保了大量人群的可及性。
We aimed to develop a novel chemical cross-linker treatment for keratoconus by reacting dicarboxylic acid spacer molecules and amine functional groups on protein structure of the tissue using carbodi-imide chemistry. We propose this as an alternative to conventional cross-linking treatment for keratoconus. The study involved optimization of the cross-linker formulation. Mechanical stiffness of ex vivo porcine and human corneas after application of the cross-linker was measured. Histochemical analysis was performed to record changes in gross morphology after cross-linker treatment on ex vivo porcine and human and in vivo rabbit corneas. Terminal deoxynucleotidyl transferase–mediated dUTP-X nick-end-labeling (TUNEL) staining was performed to study apoptotic effects of cross-linker. Cytotoxicity potential of cross-linker was evaluated by studying explant cultures for cellular outgrowth and immunostaining assays on porcine and human corneas after treatment. We demonstrated a clinically relevant increase in stiffness in ex vivo experiments using porcine and human cornea without removal of corneal epithelium. Histological analysis showed no change in gross morphology of cornea and no evidence of apoptosis. In vivo treatment of rabbit eyes demonstrated initial thinning of corneal epithelium that recovered after seven days although with abnormal regularity of cells. Cellular outgrowth from corneal explant cultures after treatment further confirmed cell survival after treatment. This chemical cross-linking of corneal tissue has potential advantages over current therapeutic options including lower cytotoxicity to stromal cells than ultraviolet A treatment. The cross-linker has potential to become a treatment for keratoconus because it overcomes the need for procedures using specialized equipment and ensures accessibility to large populations.
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影响因子：
4.1
作者：
TAYLOR, MJ;HUNT, CJ
通讯作者：
HUNT, CJ
影响因子：
0.6
作者：
Jankov Ii MR;Jovanovic V;Nikolic L;Lake JC;Kymionis G;Coskunseven E
通讯作者：
Coskunseven E
影响因子：
2.8
作者：
Kim, Su-Young;Babar, Natasha;Paik, David C.
通讯作者：
Paik, David C.
影响因子：
14
作者：
Merrett, Kimberley;Liu, Wenguang;Fogg, Deryn E.
通讯作者：
Fogg, Deryn E.
影响因子：
2.8
作者：
Ghanem, Vinicius C.;Ghanem, Ramon C.;de Oliveira, Renan
通讯作者：
de Oliveira, Renan