Professor: Yongxiong Chen
Postgraduate students: Sangang Wu, Ting Su, Mingda Li, Xulin Liao, Yunpeng Li, Pusheng Xu
Cell and molecular mechanisms regulating angiogenesis in ocular diseases
Ocular neovascularization (CNV), an abnormal growth of blood vessels in the eye, is associated with various disorders and often causes severe loss of vision, eventually blindness. The mechanism of this new blood vessel formation remains unclear and is thought to be a complex process of sprouting of new capillaries from pre-existing vessels, characterized by a cascade of events: initial vasodilatation of existing vessels is accompanied by increased vascular permeability and degradation of the surrounding matrix, which allows activated and proliferating vascular endothelial cells(VECs) to migrate and form tubes. The multistep process of angiogenesis is tightly controlled by a dynamic balance between angiogenic and anti-angiogenic regulators. Bone marrow-derived precursor endothelial cell or angioblast is described to incorporate into sites of active angiogenesis. In the present study, however, we found that CNV did not occur although chicken corneas expressed markedly angiogenic factors and matrix metalloproteinases as same as mice corneas after alkali burns. Moreover, we found that keratocytes could directly degrade extracellular matrix (ECM) to create spaces into which VECs could migrate, and there was no sign of VECs proliferation in CNV. We are going to unravel the new mechanism of CNV and identify related cellular and molecular “players” in this mechanism. Elucidating the exact cellular and molecular mechanisms of angiogenesis will open new therapeutic approaches to prevent invision loss in ocular diseases.
Origin and function of corneal dendritic cells
Bone marrow stem cells (BMSCs) derived dendritic cells (DCs) are most efficient antigen-presenting cells (APCs) which control immune responses. The cornea is endowed with different types and subsets resident dendritic cells. They are considered to be derived from BMSCs and play a critical role in corneal transplant rejection and viral keratitis. The phenotypic and functional features of corneal DCs derived from BMSCs are needed to be assessed in corneal transplant rejection and viral keratitis. We will investigate the related factors that move BMSCs from blood to cornea, and some major signaling pathways that induce BMSCs to differentiate into different resident DCs in cornea and these DCs apoptosis in herpes simplex virus-1 (HSV-1) infection through the mice models of corneal graft rejection and herpes simplex keratitis built up on some transgenic mouse strains. This project will reveal that depletion of some subsets of BMSCs is useful to abating and preventing corneal graft rejection. The evidences from this study are also useful to elucidate the pathogenesis of herpes simplex keratitis.
1. Liying Tang, Xue Wang, Jieli Wu, Sanming Li, Zhaoqiang Zhang, Sangang Wu, Ting Su, Zhirong Lin, Xueting Chen, Xulin Liao, Ting Bai, Yan Qiu, Peter Sol Reinach, Wei Li, Yongxiong Chen, Zuguo Liu. Sleep Deprivation Induces Dry Eye through Inhibition of PPARα Expression in Corneal Epithelium. Invest Ophthalmol Vis Sci. 2018, in press
2. Wu SG, Zhang WW, He ZY, Sun JY, Chen YX, Guo L. Sites of metastasis and overall survival in esophageal cancer: a population-based study. Cancer Manag Res. 2017 Dec 6;9:781-788.
3. Wu SG, Zhang WW, Sun JY, Li FY, Chen YX, He ZY. Postoperative radiotherapy for invasive micropapillary carcinoma of the breast: an analysis of Surveillance, Epidemiology, and End Results database. Cancer Manag Res. 2017 Oct 3;9:453-459.
4. 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): 8111-8122.
5. 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.
6. Chen Y, Hwang SL, Chan VS, Chung NP, Wang SR, Li Z, Ma J, Lin CW, Hsieh YJ, Chang KP, Kung SS, Wu YC, Chu CW, Tai HT, Gao GF, Zheng B, Yokoyama KK, Austyn JM, Lin CL. Binding of HIV-1 gp120 to DC-SIGN promotes ASK-1-dependent activation-induced apoptosis of human dendritic cells. PLoS Pathogens. 2013;9(1):e1003100.