Unit on Retinal Vascular Neurobiology

Dr. Xuri Li
lixur@mail.nih.gov
(301) 496-4103

On this page:

• Research Interests
• Research Summary
• Selected Publications

(from left to right) Zhongshu Tang, Ph.D., Visiting Fellow; Chunsik Lee, Ph.D., Visiting Fellow; Susan Dailey, Administrative Laboratory Manager; Anil Kumar Chikkasidde Gowda, Visiting Fellow; Xuri Li,Ph.D., Principal Investigator; Zhang Fan, Ph.D., Visiting Fellow; Pachippan Arjunan, Ph.D., Visiting Fellow; Xu Hou, Ph.D., Visiting Fellow; Yang Li, Ph.D., Contractor.

Research Interests

The major scientific interest of the Unit of Vascular Retinal Neurobiology Research is to understand the process of angiogenesis/vasculogenesis and neurogenesis in the retina in development, normal physiology and various pathologies and to use the gained knowledge to explore better therapies for treating human neural vascular diseases. We are also interested in understanding the basic cellular and molecular mechanisms underlying the interactions among retinal neurons, glia, and vascular cells.

Research Summary

Four major research areas are currently active in our unit.

1. Neuroprotection by growth factors in glaucoma.
   Glaucoma is the most prevalent form of adult optic neuropathy. It is characterized by increased rate of apoptosis of retinal ganglion cells, loss of optic nerve fibers, and eventually impairment or loss of vision. The number of patients with glaucoma related pathologies is significantly increasing because of population ageing. Many risk factors contribute to the development of glaucoma, and there is currently no general treatment effective for all glaucoma patients. Recently, neuroprotection as achieved by neurotrophic factors has emerged to be one general strategy for glaucoma treatment. However, the number of such neuroprotective factors is still limited. We are currently using multiple approaches including protein and gene delivery, normal and transgenic mice, gain and loss of function studies to investigate the neuroprotective effect of several growth factors on retinal ganglion cells.
2. Targeting angiogenic growth factors in ocular neovascular diseases
   Neovascular age-related macular degeneration (AMD) is the major cause of blindness in old population in the Western society because of the outgrowth of new blood vessels from choroids into retina, resulting in retina detachment. Many angiogenesis inhibitors have been tested for neovascular AMD treatment and beneficial effects have been demonstrated. However, the progression of this pathology cannot be halted or reversed. New anti-angiogenic reagents are therefore still awaited. Studies characterizing new molecules playing important roles in choroidal neovascularization are therefore greatly awaited. PDGFs and their receptors have become critical targets in anti-angiogenic therapy. However, the role of PDGF-C and PDGF-D in AMD choroidal neovascularization (CNV) is thus far unknown. Ongoing work in our unit concerns the angiogenic activity of PDGF-C and PDGF-D in CNV formation and development, and the potential use of PDGF-C/D and their receptor targeting in CNV treatment.
3. Effect of PDGFs and VEGFs on adult retinal stem cells
   Each year, millions of patients suffer from vision loss because of irreversible loss of neural cells in the eye due to neurodegeneration. Thus far, there is no cure for such degenerative diseases as neural cells are not capable of regeneration. Cell therapy using eye stem cells to make new neural cells thus offers hope to patients with neurodegenerative diseases. A better understanding of the regulation of eye stem cells is therefore crucial. PDGF-A and PDGF-B have been shown to play important roles in the proliferation and differentiation of different types of stem cells. The potential effect of PDGF-C and PDGF-D on ocular stem cells remains unclear thus far. We are currently investigating this.
4. Role of PDGFs and VEGFs in retina development
   During development, the cell fate is determined by many molecules and by the interactions among different types of cells and their microenvironment. Studying this process may provide enormous insight into the biological function of different molecules and the mechanism governing the fate-making of embryonic stem cells. We are using multiple approaches, such as protein and gene delivery for gain of function studies and RNAi and neutralizing antibody for loss of function studies, to pinpoint the potential effect of the PDGFs in retinal development and the underlying mechanisms.

Selected Publications

1. Li X, Tjwa M, Van Hove I, Enholm B, Neven E, Paavonen K, Jeltsch M, Juan TD, Sievers RE, Chorianopoulos E, Wada H, Vanwildemeersch M, Noel A, Foidart JM, Springer ML, von Degenfeld G, Dewerchin M, Blau HM, Alitalo K, Eriksson U, Carmeliet P, Moons L., Reevaluation of the Role of VEGF-B Suggests a Restricted Role in the Revascularization of the Ischemic Myocardium, Arterioscler Thromb Vasc Biol, 28(9):1614-1620, 29, 2008 PubMed
Related information:
• ATVB Editorial comment: VEGF-B taken to our hearts, Arterioscler Thromb Vasc Biol, 28(9):1575-1576, 29, 2008
2. Li Y, Zhang F, Nagai N, Tang Z, Zhang S, Scotney P, Lennartsson J, Zhu C, Qu Y, Fang C, Hua J, Matsuo O, Fong GH, Ding H, Cao Y, Becker KG, Nash A, Heldin CH, Li X.; VEGF-B inhibits apoptosis via VEGFR-1-mediated suppression of the expression of BH3-only protein genes in mice and rats, J ClinInvest, 118(3): 913–923, 2008 PubMed
3. Li X, Tjwa M, Moons L, Fons P, Noel A, Ny A, Zhou JM, Lennartsson J, Li H, Luttun A, Pontén A, Devy L, Bouché A, Oh H, Manderveld A, Blacher S, Communi D, Savi P, Bono F, Dewerchin M, Foidart JM, Autiero M, Herbert JM, Collen D, Heldin CH, Eriksson U, Carmeliet P. Revascularization of ischemic tissues by PDGF-CC via effects on endothelial cells and their progenitors. J Clin Invest 2005; 115(1):118-127 PubMed
Related information:
• Featured News: Platelet-derived growth factor CC--a clinically useful angiogenic factor at last?, N Engl J Med, 2005, 352(17): 1815-1816
• JCI Article In The News: PDGF-CC, the best thing ever since sliced bread?, J Clin Invest 2005, 115(1)
4. Li X, Eriksson U. Novel PDGF family members: PDGF-C and PDGF-D. Cytokine & Growth Factor Rev 2003; 244: 1-8 PubMed
5. Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin CH, Alitalo K, Eriksson U. PDGF-D is a specific, protease-activated ligand for the PDGF beta-Receptor. Nat Cell Biol 2001; 3(5): 515-516 PubMed
6. Li X, Eriksson U. Novel VEGF family members: VEGF-B, VEGF-C and VEGF- D. Int J Biochem Cell Biol 2001; 33(4): 421-426 PubMed
7. Li X, Pontén A, Aase K, Karlsson L, Abramsson A, Uutela M, Bäckström G, Hellström M, Boström H, Li H, Soriano P, Betsholtz C, Heldin CH, Alitalo K, Ostman A, Eriksson U. PDGF-C is a new protease-activated ligand for the PDGF- α receptor. Nat Cell Biol 2000; 2(5): 302-309) PubMed