A study on the therapeutic role of a Chinese medicine on the corneal injury using a microfluidic eye-on-a-chip
Yau Kei CHAN
Department of Ophthalmology, The University of Hong Kong
jchanyk@hku.hk
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.
Reference:
1. Khamar, P., et al., Early biological responses in ocular tissue after SMILE and LASIK surgery. Exp Eye Res, 2020. 192: p. 107936.
2. Whitcher, J.P., M. Srinivasan, and M.P. Upadhyay, Corneal blindness: a global perspective. Bull World Health Organ, 2001. 79(3): p. 214-21.
3. Jester, J.V., et al., Induction of alpha-smooth muscle actin expression and myofibroblast transformation in cultured corneal keratocytes. Cornea, 1996. 15(5): p. 505-16.
4. Luo, Q., et al., Hypoglycemic and hypolipidemic effects and antioxidant activity of fruit extracts from Lycium barbarum. Life Sci, 2004. 76(2): p. 137-49.
5. Zhang, L., et al., A study on four antioxidation effects of lycium barbarum polysaccharides in vitro. Afr J Tradit Complement Altern Med, 2013. 10(6): p. 494-498.
6. Mao, F., et al., Anticancer effect of Lycium barbarum polysaccharides on colon cancer cells involves G0/G1 phase arrest. Med Oncol, 2011. 28(1): p. 121-6.
7. Yang, D., K.F. So, and A.C. Lo, Lycium barbarum polysaccharide extracts preserve retinal function and attenuate inner retinal neuronal damage in a mouse model of transient retinal ischaemia. Clin Exp Ophthalmol, 2017. 45(7): p. 717-729.
8. Gan, L., et al., Immunomodulation and antitumor activity by a polysaccharide-protein complex from Lycium barbarum. Int Immunopharmacol, 2004. 4(4): p. 563-9.
9. Gan, F., et al., Lycium barbarum polysaccharides improve CCl4-induced liver fibrosis, inflammatory response and TLRs/NF-kB signaling pathway expression in wistar rats. Life Sci, 2018. 192: p. 205-212.
10. Wu, P.S., et al., Hot water extracted Lycium barbarum and Rehmannia glutinosa inhibit liver inflammation and fibrosis in rats. Am J Chin Med, 2011. 39(6): p. 1173-91.
11. Kwok, S.S., et al., Lycium barbarum Polysaccharide Suppresses Expression of Fibrotic Proteins in Primary Human Corneal Fibroblasts. J Clin Med, 2020. 9(11).
Short Bio
YK Chan has a biomedical engineering background and dedicates himself to apply bioengineering technologies in the field of ophthalmology. His research interest lies on the design and testing of ophthalmic biomaterials, surgical tools and diagnostic tools, and the development of eye-on-a-chip microfluidic platforms for physiologically relevant studies in eye research. In the meantime, he is also exploring the use of all-aqueous immiscible liquid-liquid system as platforms to form cellular structures for potential cell transplantation purposes in the cornea. He also works very closely with many ophthalmologists, and gets involved in many clinical studies of the treatments for glaucoma and other retinal diseases.