Research Specialist:Yun Han
Research assistant:Hui He
Postgraduate students:Changkai Jia, Xin Che, Jinghua Bu, Jia He, Chengyou Zuo, Shangkun Ou, Xin He, Jingwen Yu, Yuli Guo.
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 clinic 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.
1. Ouyang H, Goldberg JL, Chen S, Li W, Xu GT, Li W, Zhang K, Nussenblatt RB, Liu Y, Xie T, Chan CC, Zack DJ. Ocular Stem Cell Research from Basic Science to Clinical Application: A Report from Zhongshan Ophthalmic Center Ocular Stem Cell Symposium. Int J Mol Sci. 2016 Mar 22;17(3). pii: E415. doi: 10.3390/ijms17030415.
2. Zhang L, Zou D, Li S, Wang J, Qu Y, Ou S, Jia C, Li J, He H, Liu T, Yang J, Chen Y, Liu Z, Li W. An Ultra-thin Amniotic Membrane as Carrier in Corneal Epithelium Tissue-Engineering. Sci Rep. 2016 Feb 15;6:21021.
3. Li J, Li C, Wang G, Liu Z, Chen P, Yang Q, Dong N, Wu H, Liu Z, Li W. APR-246/PRIMA-1Met Inhibits and Reverses Squamous Metaplasia in Human Conjunctival Epithelium. Invest Ophthalmol Vis Sci. 2016 Feb 1;57(2):444-52.
4. Wang Y, Li S, Chen X, Ma B, He H, Liu T, Yu J, Zhang L, Chen Y, Liu Z, Li W. Meibomian gland absence related dry eye in ectodysplasin A mutant mice. Am J Pathol. 2016 Jan;186(1):32-42.
5. Shao Y, Tang J, Zhou Y, Qu Y, He H, Liu Q, Tan G, Li W*, Liu Z*. A novel method in preparation of acellular porcine corneal stroma tissue for lamellar keratoplasty. Am J Transl Res. 2015 Dec 15;7(12):2612-29.
6. Liu Z, Qiu F, Li J, Zhu Z, Yang W, Zhou X, An J, Huang F, Wang Q, Reinach PS, Li W, Chen W, Liu Z. Adenomatous polyposis coli mutation leads to myopia development in mice. PLoS One. 2015 Oct 23;10(10):e0141144.
7. Dong F, Liu CY, Yuan Y, Zhang Y, Li W, Call M, Zhang L, Chen Y, Liu Z, Kao WW. Perturbed meibomian gland and tarsal plate morphogenesis by excess TGFα in eyelid stroma. Dev Biol. 2015 Oct 15;406(2):147-57.
8. Poon MW, He J, Fang X, Zhang Z, Wang W, Wang J, Qiu F, Tse HF, Li W, Liu Z, Lian Q. Human ocular epithelial cells endogenously expressing sox2 and oct4 yield high efficiency of pluripotency reprogramming. PLoS One. 2015 Jul 1;10(7):e0131288.
9. Han Y, Shao Y, Liu TT, Qu YL, Li W*, Liu Z*. Therapeutic Effects of Topical Netrin-4 Inhibits Corneal Neovascularization in Alkali Burn Rats. PLoS One. 2015 Apr 8;10(4):e0122951.
10. Han Y, Shao Y, Liu TT, Li SM, Li W, Liu ZG. Therapeutic effects of topical netrin-4 in a corneal acute inflammatory model. Int J Ophthalmol. 2015 Apr 18;8(2):228-33.
11. Huang C, Wang H, Pan J, Zhou D, Chen W, Li W, Chen Y, Liu Z. Benzalkonium Chloride Induces Subconjunctival Fibrosis Through the COX-2-Modulated Activation of a TGF-β1/Smad3 Signaling Pathway. Invest Ophthalmol Vis Sci. 2014 Nov 18;55(12):8111-22.
12. Ma J, Zhou D, Fan M, Wang H, Huang C, Zhang Z, Wu Y, Li W, Chen Y, Liu Z. Keratocytes create stromal spaces to promote corneal neovascularization via MMP13 expression. Invest Ophthalmol Vis Sci. 2014 Sep 4;55(10):6691-703.
13. Hu P, Zheng XS, Zong C, Li MH, Zhang LY, Li W*, Ren B*. Drop-coating deposition and surface-enhanced Raman spectroscopies (DCDRS and SERS) provide complementary information of whole human tears. J Raman Spectrosc. 2014, Jun; 45(6): 565–573.
14. Ma B, He X, Li W. [Research progress in the metabolism of corneal epithelial cells]. Chin J Cell Stem Cell. 2014, Feb; 4(1):72-78.
15. Qu Y, Lin H, Geng Z, He H, Liu Z, Li W. [The phenotype study of murine corneal epithelial progenitor cell line TKE2]. Chin J Cell Stem Cell. 2014, Feb; 4(1):21-25.
16. Lin H, Qu Y, Geng Z, Li C, Wu H, Dong N, Liu Z, Li W. Air exposure induced characteristics of dry eye in conjunctival tissue culture. PLoS One. 2014 Jan 31;9(1):e87368.
17. Li C, Dong F, Jia Y, Du H, Dong N, Xu Y, Wang S, Wu H, Liu Z, Li W. Notch Signal Regulates Corneal Endothelial-to-Mesenchymal Transition. Am J Pathol. 2013 Sep;183(3):786-95.
18. Li C, Dong N, Wu H, Dong F, Xu Y, Du H, He H, Liu Z, Li W. A novel method for preservation of human corneal limbal tissue. Invest Ophthalmol Vis Sci. 2013 Jun 10;54(6):4041-7.
19. Sabater AL, Guarnieri A, Espana EM, Li W, Prósper F, Moreno-Montañés J. Strategies of human corneal endothelial tissue regeneration. Regen Med. 2013 Mar;8(2):183-95.
20. Xu K, Tao T, Jie J, Lu X, Li X, Mehmood MA, He H, Liu Z, Xiao X, Yang J, Ma JX, Li W, Zhou Y, Liu Z. Increased importin 13 activity is associated with the pathogenesis of pterygium. Mol Vis. 2013;19:604-13.
21. Kawakita T, Espana EM, Higa K, Kato N, Li W, Tseng SC. Activation of Smad-mediated TGF-β signaling triggers epithelial-mesenchymal transitions in murine cloned corneal progenitor cells. J Cell Physiol. 2013 Jan; 228(1):225-34.
22. Liu Z, Li W, Liang L, Liu J. Porcine Corneal Equivalent for Xenographs. Science, 2012 Apr, suppl P24-26.
23. Han Y, Shao Y, Lin Z, Quyang L, Wang H, Zhou Y, Chen W, Chen Y, Chen WL, Hu FR, Li W*, Liu Z*. Netrin-1 Simultaneously Suppresses Corneal Inflammation and Neovascularization. Invest Ophthalmol Vis Sci. 2012 Mar;53(3):1285-95.
24. Tan Y, Qiu F, Qu YL, Li C, Shao Y, Xiao Q, Liu Z, Li W. Amniotic Membrane Inhibits Squamous Metaplasia of Human Conjunctival Epithelium. Am J Physiol Cell Physiol. 2011 Jul;301(1):C115-25.
25. Li C, Yin T, Dong N, Dong F, Fang X, Qu YL, Tan Y, Wu H, Liu Z, Li W. Oxygen tension affects terminal differentiation of corneal limbal epithelial cells. J Cell Physiol. 2011 Sep;226(9):2429-37.