Ophthalmic Innovation Center, SANTEN SAS, Evry, France.
Research and Development Division, SANTEN Pharmaceutical Co., Ltd., Osaka, Japan.
Curr Eye Res. 2021 Aug;46(8):1096-1104. doi: 10.1080/02713683.2021.1878228. Epub 2021 Feb 15.
PURPOSE/AIM: Dry eye (DE) disease is a multifactorial disease in which uncontrolled inflammation can lead to corneal epithelium lesions and symptoms of discomfort. The aim of the present study was to evaluate the efficacy of two cyclosporine emulsions in a mouse model of DE with corneal epithelium lesions.
Six- to 9-week-old female C57BL/6 N mice were housed in a controlled-environment room to induce DE. Following DE development, mice were instilled with: QD 0.1%CsA cationic emulsion (CaEm), BID 0.05%CsA anionic emulsion (AEm), or left untreated. Aqueous tear production and corneal epithelium lesions were assessed throughout the experiment. At the end of the treatment period, left eyes were sampled, fixed, and stained for histology, while the cornea, conjunctiva, and lacrimal gland of right eyes were sampled for transcriptomic analysis.
Corneal lesion scores were reduced by 10.4%, 18.4%, and 10.9% at day 6, 10, and 14, respectively, with CaEm (QD), and by 2.6%, 3.0%, and 5.5% at day 6, 10, and 14, respectively, with AEm (BID). Histology demonstrated that 7 out of 10 DE mice presented moderate to severe ocular lesions, while only 2 and 5 out of 10 mice presented slight to moderate ocular lesions when treated with the CaEm (QD) and AEm (BID), respectively. The transcriptomic profile analysis suggests that a different set of inflammatory genes are modulated in the cornea, conjunctiva, and lacrimal gland upon DE development. In addition, the two emulsions distinctively modulate the gene expression profile.
This study demonstrates that both emulsions were effective at reducing corneal lesions, with the CaEm (QD) being slightly better than the AEm (BID). Interestingly, this study suggests that ocular tissues may not respond similarly to a dry environment and that a different set of genes is modulated by the two formulations in the ocular tissues.
干眼症（DE）是一种多因素疾病，其中失控的炎症可导致角膜上皮损伤和不适症状。本研究的目的是评估两种环孢素乳液在具有角膜上皮损伤的 DE 小鼠模型中的疗效。
将 6 至 9 周龄的雌性 C57BL/6N 小鼠饲养在受控环境室中以诱导 DE。DE 发展后，给小鼠滴注：QD 0.1%环孢素阳离子乳液（CaEm）、BID 0.05%环孢素阴离子乳液（AEm）或不治疗。整个实验过程中评估泪液产生和角膜上皮损伤。在治疗期结束时，取样左眼进行组织学固定和染色，同时取样右眼的角膜、结膜和泪腺进行转录组分析。
在第 6、10 和 14 天，CaEm（QD）分别使角膜病变评分降低 10.4%、18.4%和 10.9%，AEm（BID）分别使角膜病变评分降低 2.6%、3.0%和 5.5%。组织学表明，10 只 DE 小鼠中有 7 只表现为中度至重度眼部病变，而在用 CaEm（QD）和 AEm（BID）治疗时，仅有 2 只和 5 只小鼠分别表现为轻度至中度眼部病变。转录组谱分析表明，在 DE 发展过程中，角膜、结膜和泪腺中调节的炎症基因不同。此外，两种乳液可明显调节基因表达谱。
本研究表明，两种乳液均可有效减少角膜病变，CaEm（QD）略优于 AEm（BID）。有趣的是，本研究表明，眼组织可能对干燥环境的反应不同，并且两种制剂在眼组织中调节不同的基因。
