Abstract
Purpose :
In this study, we investigated the potential of dicaffeoylquinic acids (diCQAs), which are polyphenols obtained from Pseudognaphalium affine (P. affine), as a novel treatment for DED.
Methods :
We isolated 1,5-, 3,4-, 3,5- or 4,5-diCQAs from the P. affine methanol extract and confirmed them based on NMR, UV, and MS spectroscopic data. Amongst 1,5-, 3,4-, 3,5- or 4,5-diCQAs, we screened for diCQA isomer(s) effective for ocular surface protection in primary cultures of corneal epithelial cells (CECs). Then we tested the therapeutic efficacy of diCQA isomer(s) in two mouse models for DED: desiccating environmental stress-induced DED and the NOD.B10.H2b mouse model of ocular SjS. Also, we compared the therapeutic effects of diCQA(s) with two commercially-available DED treatments: 0.05% cyclosporine ophthalmic emulsion (Restasis®, Allergan, Irvine, CA) and 0.1% sodium hyaluronate eye drops (Hyalein mini 0.1%®, Santen, Osaka, Japan).
Results :
Initial screening showed that, among the diCQAs, 1,5-diCQA significantly inhibited apoptosis and enhanced viability in cultures of human CECs under desiccating hyperosmolar stress. Moreover, 1,5-diCQA protected CECs against hyperosmolar stress by promoting proliferation and downregulating inflammatory activation. Subsequent studies with two murine models of DED revealed that topical 1,5-diCQA administration dose-dependently decreased corneal epithelial defects and increased tear production while repressing inflammatory cytokines and T cell infiltration on the ocular surface and in the lacrimal gland. 1,5-diCQA was more effective in alleviating clinical signs of DED, as compared with two commercially-available dry eye treatments, 0.05% cyclosporine and 0.1% sodium hyaluronate eye drops.
Conclusions :
Together, our results demonstrate that 1,5-diCQA isolated from P. affine ameliorates DED through protection of corneal epithelial cells and suppression of inflammation, thus suggesting a novel DED therapeutic strategy based on natural compounds.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.