Professor: Yongxiong Chen
Ph.D. Candiadate: Zhaoqiang Zhang
Postgraduate Students: Liying Tang, Xue Wang, Xueting Chen
Cellular 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 bring new therapeutic approaches to prevent vision 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 are investigating 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. We are also looking into apoptosis of DCs through 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 evidence from this study is also useful to elucidate the pathogenesis of herpes simplex keratitis.
1. 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.
2. Wu SG, Rao MY, Zhou J, Lin Q, Wang ZJ, Chen YX*, He ZY*. Distribution of metastatic disease in the brain in relation to the hippocampus: a retrospective single-center analysis of 6064 metastases in 632 patients. Oncotarget. 2015 Dec 22;6(41):44030-6.
3. 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.
4. Wang X, Cao K, Sun X, Chen Y, Duan Z, Sun L, Guo L, Bai P, Sun D, Fan J, He X, Young W, Ren Y.Macrophages in spinal cord injury: Phenotypic and functional change from exposure to myelin debris. Glia. 2015 Apr;63(4):635-51.
5. 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.
6. 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.
7. Zhang Z, Yang WZ, Zhu ZZ, Hu QQ, Chen YF, He H, Chen Y, Liu ZG.Therapeutic Effects of Topical Doxycycline in a Benzalkonium Chloride-Induced Mouse Dry Eye Model. Invest Ophthalmol Vis Sci. 2014 May 6;55(5):2963-74.
8. 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.