William Brunken PhD
SUNY Upstate, Ophthalmology
Current Position: Professor and Director of Center for Vision Research
Keywords Research Areas: synapse formation; extracellular matrix; Müller Cell; neovascularization; retinal degeneration; neural prostheses
Research Focus:
  • Corneal Diseases
  • Fundamental Retinal Processes
  • Retinal Diseases
  • Retinal Neuroscience
Clinical Relevance:
  • Age-Related Macular Degeneration
  • Corneal/Anterior Segment Diseases
  • Diabetic Retinopathy
  • Retinitis Pigmentosa/Retinal Degenerations
  • Vascular Diseases
Synopsis Of Research:

The Müller cells (MCs) have a key role in retinal homeostasis. They are polarized with an apical compartment facing the subretinal space, and a basal surface adhering to the inner limiting membrane (ILM).  Disruption of either compartment leads to activation of MCs and pathobiological consequences leading to vision loss. Laminins are key organizing molecules of basement membranes (BM), such as the ILM, and they serve as attachment sites for cell adhesion, polarity and proliferation. We produced null mutations in mice of two laminin genes, Lamb2 and Lamc3, and found that these molecules are necessary for normal retinal development. The retinal defects in the Lamb2/c3 nulls include: ILM malformation; MC disorganization and OLM disruption; photoreceptor dysgenesis; and progressive pathology in the inner retina. Our long-range goal is to understand the molecular contributions of laminin to the development and stability of MC organization, in particular, as it relates to the functional architecture of the retina.  Our immediate goal is to assess the organizing hypothesis that Müller cell-laminin interactions are critical for: 1) establishing MC polarity; 2) maintaining MC subcellular organization and 3) stabilizing the structural integrity of the neural retina.

Our work will contribute significantly to the understanding of several congenital disorders o affecting the eye including some forms of Walker-Warburg, Bardet-Biedl, Pierson's Syndrome as well as the pathophysiology of gliosis and proliferative vitreoretinopathy.

Current Or Representative Publications:
  1. Egles, C., Claudepierre, T., Manglapus, M.K., Champliaud, M-F., Brunken, W.J., and Hunter, D.D. Precise Organization of CNS Synapses Requires Laminins Containing the b2 Chain. Molecular and Cellular Neuroscience 34: 288-298. 2007
  2. Schneiders, F.I., Maertens, B., Böse, K., Li, Y., Brunken W.J., Paulsson, M., Smyth, N., and Koch, M. Binding of netrin-4 to laminin short arms regulates basement membrane assembly. J Biol Chem. 282: 23750 – 23758. 2007
  3. Denés, V., Witkovsky, P., Koch, M., Hunter, D.D., Pinzón-Duarte, G., and Brunken, W.J.  Laminin Deficits Induce Alterations in the Development of Dopaminergic Neurons in the Mouse Retina.  Visual Neuroscience  24: 549-562. 2007
  4. Nakamura, R.E.I., Hunter, D.D., Yi, H., Brunken W.J.  and Hackam, A.S. Identification of two novel activities of the Wnt signaling regulator Dickkopf 3 and characterization of its expression in the mouse retina. BioMed Central Cell Biology  8: 52  2007  Designated Highly Accessed  - over 5,200 views.
  5. Pinzón-Duarte, G., Daly, G., Yong, Li, Hunter, D.D., Koch, M. and Brunken, W.J. Genetic Deletion of Both β2 and γ3 Laminin Chains Produces Retinal Dysplasia. Investigative Ophthalmology and Visual Sciences  51: 1773-1782  2010
  6. Hirrlinger, P.G., Pannicke, T., Winkler, U., Claudepierre, T., Varshney, S., Schulze, C., Reichenbach, R., Brunken, W.J., and Hirrlinger, J. Genetic deletion of laminin isoforms β2 and γ3 induces a reduction in Kir4.1 and aquaporin-4 expression and function in the retina. PLoSOne. 6(1): e16106. doi:10.1371/journal.pone.0016106.34 2011
  7. Barak. T., Kwan, K.Y., Louvi,A., Demirbilek, V., Saygı, S., Tüysüz, B., Choi, M., Boyacı, H.,   Doerschner, K., Zhu, Y., Kaymakçalan, H., Yılmaz, S., Bakırcıoğlu, M., Çağlayan, A.O., Öztürk, A.K., Yasuno, K., Brunken, W.J., Atalar, E., Yalçınkaya, C., Dinçer, A., Bronen, R.A., Mane, S.,  Özçelik, T., Lifton, R.P.,  Šestan, N., Bilgüvar, K., Günel, M., Recessive LAMC3 mutations cause malformations of the occipital cortical development. Nature Genetics. 43:590-594. PMID: 21572413  2011
  8. Saghizadeh, M., Soleymani, S., Harounian, A., Bhakta, B., Troyanovsky, S.M., Brunken, W.J., Pellegrini,G., and Ljubimov, A.V. Alterations of epithelial stem cell marker patterns in human diabetic corneas and effects of c-met gene therapy. Molecular Vision 17:2177-2190. 2011
  9. Yebra, M., Diaferia, G.R., Montgomery, A.M., Kaido, T., Brunken, W.J., Koch, M., Hardiman, G., Crisa, L., and Cirulli, V. Endothelium-Derived Netrin-4 Supports Pancreatic Epithelial Cell Adhesion and Differentiation through Integrins α2β1 and α3β1. PLoS One 6(7):e22750. 2011
  10. Li, Y.N., Radner, S., French, M.M., Pinzón-Duarte, G., Daly, G.H., Burgeson, R.E., Koch, M, and Brunken, W.J.  The γ3 chain of laminin is widely expressed and contributes to basement membranes in mouse: Expression and Functional Studies. Matrix Biology 31:120-134. 2012
  11. Li, Y.N., Pinzón-Duarte, G., Dattilo, M., Claudepierre, T., Koch, M., and Brunken, W.J. The Expression And Function Of Netrin-4 In Murine Ocular Tissue. Experimental Eye Research 96: 24-35 PMID: 22281059 2012
  12. Radner, S, Banos, C., Bachay, G., Li, Y.N., Hunter D. D., Brunken, W.J. and Yee, K.T. β2 and γ3 Laminins Are Critical Cortical Basement Membrane Components: Ablation of Lamb2 and Lamc3 Genes Disrupts Cortical Lamination and Produces Dysplasia. Developmental Neurobiology, 73: 209-229 2013 PMID: 22961762
  13. Gnanaguru, G., Bachay, G., Biswas, S., Pinzón-Duarte, G.A., Hunter, D.D., and Brunken, W.J., Laminins Containing the β2 and γ3 Chains Regulate Astrocyte Migration And Angiogenesis In the Retina.   Development 140: 2050-2061 2013 PMID: 23571221

State University of New York Medical Centers & College of Optometry Consortium

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