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HYEON JEONG YOON, Ying Li, Ru Jun Jin, Jung-Han Choi, Jae Hoon Yu, Kyung Chul Yoon; Anti-Inflammatory Effect of a Mixture of Cyclosporine A and Cell Penetrating Peptides in Corneal Epithelium Cells and Experimental Dry Eye: in vivo and in vitro Study. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3836.
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© ARVO (1962-2015); The Authors (2016-present)
To evaluate the efficacy of a topical mixture of cyclosporine A (CsA) and cell penetrating peptides (CPP, dimer c) which has a drug concentration of 1/100-1/10,000 with that of a conventional CsA 0.05% emulsion, in human corneal epithelium (HCE) cells and experimental dry eye (EDE) model.
CsA 0.05% and CsA-CPP (10-nM) were applied to HCE cells. Interleukin (IL) levels were determined using a RT-PCR. Experimental dry eye was established in female C57BL/6 mice with subcutaneous scopolamine injection and an air draft. The mice were divided into 6 groups (n = 90): EDE control, balanced salt solution (BSS), and 40-nM, 400-nM, and 4,000-nM CsA-CPP, or CsA 0.05% (400-μM). The tear volume, tear film break-up time (TBUT), corneal fluorescein staining score, and corneal surface irregularity were measured 5 and 10 days after treatment. Conjunctival and lacrimal gland tissues were excised at 10 days and the percentage of CD4+CCR5 T cells was analyzed using flow cytometry.
Compared with CsA 0.05% treatment, 10-nM CsA-CPP similarly decreased the levels of IL-1b, -2, -6, and -8 in HCE cells. Mice treated with CsA 0.05% and all CsA-CPP mixtures (40-4,000 nM) showed a significant improvement in TBUT, corneal fluorescein staining scores, and corneal surface irregularity, compared with the EDE control and BSS groups at 5 and 10 days after treatment. A significant decrease in the percentage of CD4+CCR5 T cell was observed in the CsA 0.05% and all CsA-CPP groups at 10 days after treatment.
Instillation of a topical CsA-CPP mixture which has a drug concentration of 1/100-1/10,000 may improve clinical signs and decrease inflammatory molecules on the ocular surface as effectively as CsA 0.05%.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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