Thathapudi Neethi C, Groleau Marc, Degué Delali S, Aghajanzadeh Kiyaseh Mozhgan, Kujawa Piotr, Soulhi Fouzia, Akla Naoufal, Griffith May, Robert Marie-Claude
Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, Canada.
Department of Ophthalmology, Université de Montréal, Montreal, QC, Canada.
Front Pharmacol. 2023 Dec 15;14:1270699. doi: 10.3389/fphar.2023.1270699. eCollection 2023.
Moderate corneal alkali burns such as those sustained from accidental exposure to household chemicals are treated with topical corticosteroids. Side effects include increased intraocular pressure and slowing of wound healing. Here, we compare the effects of a cannabinoid receptor 2 (CB2r) agonist, TA-A001, that is involved in wound healing with that of the corticosteroid, prednisolone. TA-A001 was encapsulated with a polymeric micelle comprising polyvinylpyrrolidone: polylactide block copolymers referred to as SmartCelle™ to allow delivery of the very hydrophobic drug. Mouse corneas were given moderate alkali burns. Different doses of TA-A001 of 0.125%, 0.25% and 0.5% were used to treat the burns in comparison to the corticosteroid, prednisolone. TA-A001 at 0.25% and 0.5% allowed for faster wound closure. However, the higher 0.5% dose also induced unwanted neovascularization. By comparison, burned corneas treated with prednisolone showed slower healing as well as disorganization of the cornea. Although 0.25% TA-A001 appeared to produce the most-optimal responses, this dose resulted in marked expression of the macrophage chemoattractant protein, MCP-1. However, there was also an increase in CD163 positive stained M2 anti-inflammatory macrophages in the TA-A001 corneas. TA-A001 treated corneas showed the presence of sensory nerve fibers throughout the corneal epithelium including the superficial cell layers as did Substance P staining. We found that TA-A001 at the 0.25% doses was able to modulate inflammation resulting from a moderate alkali burn to the cornea. With more extensive testing, TA-A001 might prove to be a potential alternative to corticosteroids for treating alkali burns or other causes of corneal inflammation.
中度角膜碱烧伤，如意外接触家用化学品所致的烧伤，采用局部皮质类固醇治疗。其副作用包括眼压升高和伤口愈合减慢。在此，我们比较了参与伤口愈合的大麻素受体2（CB2r）激动剂TA - A001与皮质类固醇泼尼松龙的效果。TA - A001用包含聚乙烯吡咯烷酮：聚丙交酯嵌段共聚物（称为SmartCelle™）的聚合物胶束包裹，以实现这种高度疏水药物的递送。对小鼠角膜进行中度碱烧伤。与皮质类固醇泼尼松龙相比，使用0.125%、0.25%和0.5%的不同剂量TA - A001治疗烧伤。0.25%和0.5%的TA - A001能使伤口更快闭合。然而，较高的0.5%剂量也会引发不必要的新生血管形成。相比之下，用泼尼松龙治疗的烧伤角膜愈合较慢且角膜结构紊乱。虽然0.25%的TA - A001似乎产生了最理想的反应，但该剂量导致巨噬细胞趋化蛋白MCP - 1明显表达。然而，TA - A001处理的角膜中CD163阳性染色的M2抗炎巨噬细胞也有所增加。TA - A001处理的角膜在整个角膜上皮包括表层细胞层都有感觉神经纤维存在，P物质染色也是如此。我们发现0.25%剂量的TA - A001能够调节中度角膜碱烧伤引起的炎症。经过更广泛的测试，TA - A001可能被证明是治疗碱烧伤或其他角膜炎症原因的皮质类固醇的潜在替代品。
