Diego Jose L, Bidikov Luke, Pedler Michelle G, Kennedy Jeffrey B, Quiroz-Mercado Hugo, Gregory Darren G, Petrash J Mark, McCourt Emily A
Department of Ophthalmology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO 80045.
Mol Vis. 2016 Sep 9;22:1095-1102. eCollection 2016.
Dry eye syndrome (DES) affects millions of people worldwide. Homeopathic remedies to treat a wide variety of ocular diseases have previously been documented in the literature, but little systematic work has been performed to validate the remedies' efficacy using accepted laboratory models of disease. The purpose of this study was to evaluate the efficacy of human milk and nopal cactus (prickly pear), two widely used homeopathic remedies, as agents to reduce pathological markers of DES.
The previously described benzalkonium chloride (BAK) dry eye mouse model was used to study the efficacy of human milk and nopal cactus (prickly pear). BAK (0.2%) was applied to the mouse ocular surface twice daily to induce dry eye pathology. Fluorescein staining was used to verify that the animals had characteristic signs of DES. After induction of DES, the animals were treated with human milk (whole and fat-reduced), nopal, nopal extract derivatives, or cyclosporine four times daily for 7 days. Punctate staining and preservation of corneal epithelial thickness, measured histologically at the end of treatment, were used as indices of therapeutic efficacy.
Treatment with BAK reduced the mean corneal epithelial thickness from 36.77±0.64 μm in the control mice to 21.29±3.2 μm. Reduction in corneal epithelial thickness was largely prevented by administration of whole milk (33.2±2.5 μm) or fat-reduced milk (36.1±1.58 μm), outcomes that were similar to treatment with cyclosporine (38.52±2.47 μm), a standard in current dry eye therapy. In contrast, crude or filtered nopal extracts were ineffective at preventing BAK-induced loss of corneal epithelial thickness (24.76±1.78 μm and 27.99±2.75 μm, respectively), as were solvents used in the extraction of nopal materials (26.53±1.46 μm for ethyl acetate, 21.59±5.87 μm for methanol). Epithelial damage, as reflected in the punctate scores, decreased over 4 days of treatment with whole and fat-reduced milk but continued to increase in eyes treated with nopal-derived materials.
Whole and fat-reduced human milk showed promising effects in the prevention of BAK-induced loss of corneal epithelial thickness and epithelial damage in this mouse model. Further studies are required to determine whether human milk may be safely used to treat dry eye in patients.
干眼症(DES)影响着全球数百万人。文献中先前已记载了用于治疗多种眼部疾病的顺势疗法药物,但利用公认的疾病实验室模型来验证这些药物疗效的系统性研究却很少。本研究的目的是评估人乳和仙人掌(刺梨)这两种广泛使用的顺势疗法药物作为减少干眼症病理标志物药物的疗效。
使用先前描述的苯扎氯铵(BAK)干眼症小鼠模型来研究人乳和仙人掌(刺梨)的疗效。每天两次将0.2%的BAK应用于小鼠眼表以诱发干眼症病理。用荧光素染色来验证动物是否有干眼症的特征性体征。诱发干眼症后,每天四次给动物用人乳(全脂和低脂)、仙人掌、仙人掌提取物衍生物或环孢素进行治疗,持续7天。治疗结束时通过组织学测量的点状染色和角膜上皮厚度的保持情况用作治疗效果的指标。
用BAK治疗使对照小鼠的平均角膜上皮厚度从36.77±0.64μm降至21.29±3.2μm。给予全脂牛奶(33.2±2.5μm)或低脂牛奶(36.1±1.58μm)在很大程度上预防了角膜上皮厚度的降低,这些结果与用环孢素(38.52±2.47μm)治疗相似,环孢素是当前干眼症治疗的标准药物。相比之下,粗制或过滤后的仙人掌提取物在预防BAK诱导的角膜上皮厚度丧失方面无效(分别为24.76±1.78μm和27.99±2.75μm),用于提取仙人掌材料的溶剂也是如此(乙酸乙酯为26.53±1.46μm,甲醇为21.59±5.87μm)。如点状评分所反映的上皮损伤在用全脂和低脂牛奶治疗的4天内有所减轻,但在用仙人掌衍生材料治疗的眼中则持续增加。
在该小鼠模型中,全脂和低脂人乳在预防BAK诱导的角膜上皮厚度丧失和上皮损伤方面显示出有前景的效果。需要进一步研究以确定人乳是否可安全用于治疗患者的干眼症。