Olivieri Melania, Cristaldi Martina, Pezzino Salvatore, Lupo Gabriella, Anfuso Carmelina Daniela, Gagliano Caterina, Genovese Carlo, Rusciano Dario
Sooft Italia SpA, Res. Dept., Catania, Italy.
BIOMETEC, University of Catania, Catania CT, Italy.
Cornea. 2018 Aug;37(8):1058-1063. doi: 10.1097/ICO.0000000000001594.
The aim of this study was to investigate the properties of lactobionic acid (LA) as a possible supplement in artificial tears in in vitro and in vivo experimental model systems. LA is a bionic derivative of a polyhydroxy acid, which consists of one galactose attached by an ether link to a gluconic acid. It is a molecule endowed with several properties that make it an ideal supplement in artificial tears: it is highly hygroscopic and a powerful antioxidant, it is an iron chelator and inhibits matrix metalloprotease activity; it favors wound healing (WH); and it inhibits bacterial growth.
Promotion of WH by LA, alone or in combination with hyaluronic acid (HA), was investigated in vitro on monolayers of rabbit corneal cells (Statens Seruminstitut) and in vivo after epithelium debridement of rabbit corneas. TGF-β expression and MMP-9 activity in wounded corneas were detected in tears and cornea extracts by western blot or by Enzyme Linked ImmunoSorbent Assay (ELISA). Bacterial growth inhibition by LA was checked on Staphylococcus aureus isolates in liquid culture.
LA, with or without HA, favors WH in vitro and in vivo. The WH assay on the rabbit cornea showed that 4% LA in association with 0.15% HA also resulted in a blunted increase of MMP-9 and TGF-β in tears and corneal tissue. Finally, the presence of 4% LA resulted in slower growth of cultured bacterial isolates.
Our findings support the hypothesis that LA could be a useful supplement to artificial tears to treat ocular surface dysfunction such as dry eye.
本研究旨在通过体外和体内实验模型系统，研究乳糖酸（LA）作为人工泪液中一种可能的补充剂的特性。LA是一种多羟基酸的仿生衍生物，由一个通过醚键连接到葡萄糖酸上的半乳糖组成。它是一种具有多种特性的分子，使其成为人工泪液中理想的补充剂：它具有高度吸湿性且是一种强大的抗氧化剂，它是一种铁螯合剂并能抑制基质金属蛋白酶活性；它有利于伤口愈合（WH）；并且它能抑制细菌生长。
在体外对兔角膜细胞单层（丹麦国家血清研究所）以及在兔角膜上皮清创术后的体内，研究LA单独或与透明质酸（HA）联合对伤口愈合的促进作用。通过蛋白质印迹法或酶联免疫吸附测定（ELISA）检测受伤角膜中泪液和角膜提取物中的转化生长因子-β（TGF-β）表达和基质金属蛋白酶-9（MMP-9）活性。在液体培养中检测LA对金黄色葡萄球菌分离株的细菌生长抑制作用。
无论有无HA，LA在体外和体内均有利于伤口愈合。兔角膜上的伤口愈合试验表明，4%的LA与0.15%的HA联合使用还导致泪液和角膜组织中MMP-9和TGF-β的增加变缓。最后，4%的LA的存在导致培养的细菌分离株生长较慢。
我们的研究结果支持以下假设，即LA可能是治疗眼表功能障碍如干眼症的人工泪液的有用补充剂。
