A study on the therapeutic role of a Chinese medicine on the corneal injury using a microfluidic eye-on-a-chip

Abstract

Corneal refractive surgeries are popular nowadays for vision correction. However, these surgeries may lead to the upregulation of transforming growth factor-beta 1 (TGF-b1), which triggers subsequent secretion of inflammatory cytokines and upregulation of profibrotic proteins. These physiological events may lead to corneal scarring if the situation gets worse.[1] Under such injury, corneal cells in the stroma of cornea will proliferate and phenotypically differentiate into myofibroblasts which are opaque.[3] This is known as corneal haze, which highly affects the vision. Lycium barbarum polysaccharide (LBP), a daily supplement,is a mixture of different polysaccharides extracted from wolfberries.[4] Many studies have already shown its various therapeutic effects such as anti-aging, neuroprotective and anti-cancer,[5-8] and also anti-fibrotic and anti-inflammatory.[9, 10] Hence, we hypothesized that LBP can be a natural pretreatment to reduce corneal scar formation with minimal cellular toxicity, and have recently justified the hypothesis in our proof-of-concept in-vitro 2D culture study.[11] In this study, an eye-on-a-chip model was used, as a more physiologically representative in-vitro model, to further understand the therapeutic potential of LBP and the underlying mechanism on reducing corneal scarring. Corneal stromal cells were cultured in a 3D collagen type I-based hydrogel within the chip. The cells were pre-treated with LBP solution for 24 hours, followed by a 24-hour incubation with TGF-b1 to induce relevant physiological events after corneal injury. The results in this study showed that LBP reduced both pro-fibrotic proteins and pro-inflammatory cytokines on TGF-b1 induced events within the eye-on-a-chip model. We suggest that LBP, in the form of a topical solution, may potentially be a novel pre-treatment option prior to corneal refractive surgeries with an improved prognosis.