Research Focus：
Corneal epithelial stem cell
Corneal epithelial stem cell, the only origination of the corneal epithelial cells, plays a pivotal role in maintaining the stability of corneal epithelium and transparency of corneal tissue. Severe corneal epithelial stem cell deficiency can cause visual impairment and blindness. Our group has been focusing on the proliferation and differentiation of corneal epithelial stem cell, limbal stem cell niche, ex vivo expansion and transplantation of limbal stem cell. We established mouse and rabbit models of corneal epithelial stem cell deficiency, modified ex vivo expansion protocol, unveiled the effect of hypoxia on the proliferation and differentiation of limbal stem cell. Moreover, we developed new limbal stem cell transplantation techniques and we are now applying these techniques in the treatment of limbal stem cell deficiency.
Amniotic membrane related tissue engineering
Amniotic membrane has been widely applied in ophthalmology and other tissue engineering areas in the past 10 years due to its special biological properties and weak immunogenicity. In ophthalmology, amniotic membrane is mainly used in the treatment of ocular surface diseases. A large number of clinical studies have shown that amniotic membrane is meditative in anti-inflammation, anti-scarring, anti-angiogenesis, as well as the promotion of the ocular surface epithelial wound healing. Our team has a strong background in amniotic membrane research. Previously, we have investigated the therapeutic mechanism of amniotic membrane in the treatment of ocular surface diseases at molecular and cellular levels. We are now interested in new applications of amniotic membrane in different medical science areas, and the development of new tissue engineered products related to amniotic membrane.
Squamous Metaplasia of the Ocular Surface Epithelium
Squamous metaplasia of the ocular surface epithelium is frequently present in various ocular surface diseases such as dry eye, Stevens-Johnson syndrome, cicatricial pemphigoid, pterygium and pinguecula. Our team has set up a squamous metaplasia tissue culture model using air-liquid interface culture of corneal limbus or conjunctival tissue, and found that p38 MAPK and Wnt signaling pathway is involved in the pathogenesis of squamous metaplasia. We also found down-regulation or silence of pax6 gene is associated with abnormal epidermal differentiation of the ocular surface epithelium. We further found that application of p38 MAPK inhibitor, re-introducing of pax6 gene, co-culture with amniotic membrane, application of amniotic membrane extract, and low oxygen tension culture environment can inhibit or reverse squamous metaplasia of ocular surface epithelium to a certain degree in ex vivo tissue culture model. We now have great interest in the clinic treatment of squamous metaplasia based on our new knowledge on this pathological process.
Educational background:
September 1996- July 1999: Tongji Medical College, Huazhong University of Science and Technology, Master's degree in Ophthalmology.
September 1989- July 1994: Department of Clinical Medicine, Wan Nan Medical College, Bachelor's degree in Medicine.
Work experience:
September 2019-present: Honorary Professor, Cardiff University, United Kingdom.
June 2018 - Present: Vice Dean, School of Medicine, Xiamen University
February 2013 - Present: Director, Department of Ophthalmology and Optometry, School of Medicine, Xiamen University
December 2014 - September 2017: Also served as Assistant Dean)
August 2008 - February 2013: Deputy Director, Department of Ophthalmology and Optometry, School of Medicine, Xiamen University
April 2011 - Present: Professor, Eye Institute, Xiamen University
March 2007 - March 2011: Associate Professor, Eye Institute, Xiamen University
May 2003 - January 2007: Postdoctoral fellow at Ocular Surface Center, Miami, USA
Scientist in the Research and Development Department at TissueTech, Inc. Miami, USA
July 1999 - May 2003: Attending physician, Department of Ophthalmology, Songgang People's Hospital, Shenzhen, Guangdong Province
Selected Publications
（link to PubMed for all publications）
1.Mao Y, Ou S, Zhu C, Lin S, Liu X, Liang M, Yu J, Wu Y, He H, Zong R, Lin Z, Liu Z, Li W. Downregulation of p38 MAPK signaling pathway ameliorates tissue engineered corneal epithelium. Tissue Eng Part A. 2022 Sep 6.
2.Yu JW, Wu YM, Dai QX, Wu H, Pan JT, Guo YL, Yan K, Zhu HM , Mao Y , Lin SJ, Li W, Liu G , Chu CC.In vivo assembly drug delivery strategy based on ultra-small nanoparticles: Toward high drug permeation and accumulation for CNV treatment. Chemical Engineering Journal.2022 Jul 8；450（1）
3.Zhao Z, Liang M, He H,Wang X, Zhu C, Li L, Liu B, Zong R, Jin Q, Wu H, Li W, Lin Z. Ovalbumin-Induced Allergic Inflammation Diminishes Cross-Linked Collagen Structures in an Experimental Rabbit Model of Corneal Cross-Linking.Front Med (Lausanne). 2022 May 26;9:762730.
4.Li S, Tang L, Zhou J, Anchouche S, Li D, Yang Y, Liu Z, Wu J, Hu J, Zhou Y, Yin J, Liu Z, Li W. Sleep deprivation induces corneal epithelial progenitor cell over-expansion through disruption of redox homeostasis in the tear film. Stem Cell Reports. 2022 May 10;17(5):1105-1119.
5.Yu Z, Hao R, Du J, Wu X, Chen X, Zhang Y, Li W, Gu Z, Yang H.A human cornea-on-a-chip for the study of epithelial wound healing by extracellular vesicles.iScience. 2022 Apr 4;25(5):104200.
6.He X, Wang S, Sun H, He H, Shi Y, Wu Y, Wu H, Liu Z, Zhuang J, Li W. Lacrimal Gland Microenvironment Changes After Obstruction of Lacrimal Gland Ducts. Invest Ophthalmol Vis Sci. 2022 Mar 2;63(3):14.
7.Wang S, He X, Li Q, Zhang Y, Hu J, Zong R, Zhuang J, Quantock AJ, Gao Y, Li W, Liu Z. Obstructive Sleep Apnea Affects Lacrimal Gland Function. Invest Ophthalmol Vis Sci. 2022 Mar 2;63(3):3.
8.Guo Y, Zhang H, Zhao Z, Luo X , Zhang M, Bu J, Liang M, Wu H , Yu J, He H, Zong R, Chen Y, Liu Z, Li W. Hyperglycemia Induces Meibomian Gland Dysfunction. Invest Ophthalmol Vis Sci. 2022 Jan 3;63(1):30.
9.Bu J, Zhang M, Wu Y, Jiang N, Guo Y, He X, He H, Jeyalatha MV, Reinach PS, Liu Z, Li W. High-Fat Diet Induces Inflammation of Meibomian Gland. Invest Ophthalmol Vis Sci. 2021 Aug 2;62(10):13.
10.Liu Z, Xiu Y, Qiu F, Zhu Z, Zong R, Zhou X, An J, Wang Q, Reinach PS, Li W, Chen W, Liu Z. Canonical Wnt signaling drives myopia development and can be pharmacologically modulated. Invest Ophthalmol Vis Sci. 2021 Jul 1;62(9):21.
11.Cheng X, He D, Liao C, Lin S, Tang L, Wang YL, Hu J, Li W, Liu Z, Wu Y, Liao Y. IL-1/IL-1R signaling induced by all-trans-retinal contributes to complement alternative pathway activation in retinal pigment epithelium. J Cell Physiol. 2021 May;236(5):3660-3674.
12.Li D, Dai Q, Chen H, Lin H , Lu Z, Zheng H ,Peng Lv , Li W , Liu G ,Chu C.Metal-organic nanostructure based on TixOy/Ruthenium reaction Units: For CT/MR Imaging-Guided X-ray induced dynamic therapy. Chem Eng J.2021 Mar;417:129262.
13.Yu J, Chu C, Wu Y, Liu G, Li W.The phototherapy toward corneal neovascularization elimination:An efficient, selective and safe strategy. Chinese Chem Lett.2020 Nov;32(1):99-101.
14.Lin X, Wu Y, Tang L, Ouyang W, Yang Y, Liu Z, Wu J, Zheng X, Huang C, Zhou Y, Zhang X, Chen Y, Li W, Hu J, Liu Z. Comparison of treatment effect and tolerance of the topical application of mizoribine and cyclosporine a in a mouse dry eye model. Transl Vis Sci Technol. 2020 Dec 15;9(13):22.
15.He X, Zhao Z, Wang S, Kang J, Zhang M, Bu J, Cai X, Jia C, Li Y, Li K, Reinach PS, Quantock AJ, Liu Z, Li W. High-fat diet-induced functional and pathologic changes in lacrimal gland. Am J Pathol. 2020 Dec; 190(12): 2387-2402.
16.He J, Ou S, Ren J, Sun H, He X, Zhao Z, Wu H, Qu Y, Liu T, Jeyalatha V, Zhang L, Li Q, Reinach PS, Quantock AJ, Hao J, Liu Z, Li W. Tissue engineered corneal epithelium derived from clinical-grade human embryonic stem cells. Ocul Surf. 2020 Oct;18(4):672-680.
17.Chu C,* Yu J, Ren E, Ou S, Zhang Y, Wu Y, Wu H, Zhang Y, Zhu J, Dai Q, Wang X, Zhao Q, Li W,* Liu Z, Chen X, Liu G*. Multimodal Photoacoustic Imaging-Guided Regression of Corneal Neovascularization: A Non-Invasive and Safe Strategy. Adv. Sci. 2020 May 29;7(14):2000346.
18.Wu Y, Wu J, Bu J, Tang L, Yang Y, Ouyang W, Lin X, Liu Z, Huang C, Quantock AJ, Ma X, Li W, Zhou Y, Liu Z. High-fat diet induces dry eye-like ocular surface damages in murine. Ocul Surf. 2020 Apr;18(2):267-276.
19.Bu J, Yu J, Wu Y, Cai X, Li K, Tang L, Jiang N, Jeyalatha MV, Zhang M, Sun H, He H, Quantock AJ, Chen Y, Liu Z, Li W. Hyperlipidemia Affects Tight Junctions and Pump Function in the Corneal Endothelium. Am J Pathol. 2020 Mar;190(3):563-576.
20.Han Y, Jiang N, Su T, Yang QC, Yan CC, Ye L, Yuan Q, Zhu PW, Li W, Liu ZG, Shao Y. Netrin-1 promotes epithelium repair in corneal injury. Int J Ophthalmol. 2020 Feb 18;13(2):206-212.
21.Bu J, Wu Y, Cai X, Jiang N, Jeyalatha MV, Yu J, He X, He H, Guo Y, Zhang M, Quantock AJ, Liu Z, Li W. Hyperlipidemia induces meibomian gland dysfunction. Ocul Surf. 2019 Jun 12. 17(4):777-786.
22.Li Y, Jin R, Li L, Yoon HJ, Choi JH, Park JH, Liu Z, Li W, Li Z, Yoon KC. Expression and Role of Nucleotide-Binding Oligomerization Domain 2 (NOD2) in the Ocular Surface of Murine Dry Eye. Invest Ophthalmol Vis Sci. 2019 Jun 3;60(7):2641-2649.
23.Che X, Wu H, Jia C, Sun H, Ou S, Wang J, Jeyalatha MV, He X, Yu J, Zuo C, Liu Z, Li W. A Novel Tissue-Engineered Corneal Stromal Equivalent Based on Amniotic Membrane and Keratocytes. Invest Ophthalmol Vis Sci. 2019 Feb 1;60(2):517-527.
24.Chu C, Ren E, Zhang Y, Yu J, Lin H, Pang X, Zhang Y, Liu H, Qin Z, Cheng Y, Wang X, Li W, Kong X, Chen X, Liu G. Zinc(II)-Dipicolylamine Coordination Nanotheranostics: Toward Synergistic Nanomedicine by Combined Photo/Gene Therapy. Angew Chem Int Ed Engl. 2019 Jan 2;58(1):269-272.
25.Tang L, Wang X, Wu J, Li SM, Zhang Z, Wu S, Su T, Lin Z, Chen X, Liao X, Bai T, Qiu Y, Reinach PS, Li W, Chen Y, Liu Z. Sleep Deprivation Induces Dry Eye Through Inhibition of PPARα Expression in Corneal Epithelium. Invest Ophthalmol Vis Sci. 2018 Nov 1;59(13):5494-5508.
26.Yang Y, Huang C, Lin X, Wu Y, Ouyang W, Tang L, Ye S, Wang Y, Li W, Zhang X, Liu Z. 0.005% Preservative-Free Latanoprost Induces Dry Eye-Like Ocular Surface Damage via Promotion of Inflammation in Mice. Invest Ophthalmol Vis Sci. 2018 Jul 2;59(8):3375-3384.
27.Jie J, Yang J, He H, Zheng J, Wang W, Zhang L, Li Z, Chen J, Vimalin Jeyalatha M, Dong N, Wu H, Liu Z, Li W. Tissue remodeling after ocular surface reconstruction with denuded amniotic membrane. Sci Rep. 2018 Apr 23;8(1):6400.
28.Li S, Ning K, Zhou J, Guo Y, Zhang H, Zhu Y, Zhang L, Jia C, Chen Y, Sol Reinach P, Liu Z, Li W. Sleep deprivation disrupts the lacrimal system and induces dry eye disease. Exp Mol Med. 2018 Mar 2;50(3):e451. doi: 10.1038/emm.2017.285.
29.Zhang X, Lin X, Liu Z, Wu Y, Yang Y, Ouyang W, Li W, Liu Z. Topical Application of Mizoribine Suppresses CD4+ T-cell-Mediated Pathogenesis in Murine Dry Eye. Invest Ophthalmol Vis Sci. 2017 Dec 1;58(14):6056-6064.
30.Wu Y, Bu J, Yang Y, Lin X, Cai X, Huang C, Zheng X, Ouyang W, Li W, Zhang X, Liu Z. Therapeutic Effect of MK2 Inhibitor on Experimental Murine Dry Eye. Invest Ophthalmol Vis Sci. 2017 Sep 1;58(11):4898-4907.
31.Jeyalatha MV, Qu Y, Liu Z, Ou S, He X, Bu J, Li S, Reinach PS, Liu Z, Li W. Function of meibomian gland: Contribution of proteins. Exp Eye Res. 2017 Oct;163:29-36.
32.Li S, Zhou J, Zhang L, Li J, Yu J, Ning K, Qu Y, He H, Chen Y, Reinach PS, Liu CY, Liu Z, Li W. Ectodysplasin A regulates epithelial barrier function through sonic hedgehog signalling pathway. J Cell Mol Med. 2018 Jan;22(1):230-240.
33.Chen J, Li Z, Zhang L, Ou S, Wang Y, He X, Zou D, Jia C, Hu Q, Yang S, Li X, Li J, Wang J, Sun H, Chen Y, Zhu YT, Tseng SCG, Liu Z, Li W. Descemet's Membrane Supports Corneal Endothelial Cell Regeneration in Rabbits. Sci Rep. 2017 Aug 1;7(1):6983.
34.Zhang X, M VJ, Qu Y, He X, Ou S, Bu J, Jia C, Wang J, Wu H, Liu Z, Li W. Dry Eye Management: Targeting the Ocular Surface Microenvironment. Int J Mol Sci. 2017 Jun 29;18(7).
35.Li S, Zhou J, Bu J, Ning K, Zhang L, Li J, Guo Y, He X, He H, Cai X, Chen Y, Reinach PS, Liu Z, Li W. Ectodysplasin A protein promotes corneal epithelial cell proliferation. J Biol Chem. 2017 Aug 11;292(32):13391-13401.
36.Wu H, Lin Z, Yang F, Fang X, Dong N, Luo S, Shang X, Li W, Liu Z. Meibomian Gland Dysfunction Correlates to the Tear Film Instability and Ocular Discomfort in Patients with Pterygium. Sci Rep. 2017 Mar 24;7:45115.
