The major focus of our laboratory is to define the mechanisms involved in the regulation of abnormal ocular angiogenesis seen in conditions such as diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration. Currently we are focused on the role of specific extracellular proteinases in angiogenesis, including the serine protease urokinase and members of the matrix metalloproteinases family of enzymes. Factors which regulate the expression and activity of the enzymes are being investigated. These studies make use of histological, biochemical and genetic techniques to examine both animal models of abnormal angiogenesis and cell cultures. A current area of emphasis is aimed at identifying inhibitors of new vessel formation in the eye with the goal of developing better treatments for these devastating ocular conditions. A second area of investigation looks at the factors and mechanisms which regulate the permeability of the blood-retinal-barrier in response to diabetes. A diabetic mouse model and cultures of retinal microvascular endothelial cells are used to determine the role of specific extracellular proteinases and growth factors in the regulation of tight junction activity.
1980, B.S., Biology, Colorado State University
1984, Ph.D., Anatomy, Colorado State University
1984-87; Research Fellow (Developmental Biology), Harvard Medical School
1987-89; Research Fellow (Biochemistry and Genetics), University of Colorado
Anupam Basu, Post Doc
Joann Maestes, HS Research Tech
Srinivasan Ramprasad, Post Doc
Deepti Navaratna, Graduate Student
McGuire, P.G. and Alexander, S.M. (1992). Urokinase Production By
Embryonic Endocardial-Derived Cells: Regulation By Substrate Composition.
Developmental Biology 155, 442-451.
McGuire, P.G. and Alexander, S.M. (1993). Inhibition Of Urokinase
Synthesis And Cell-Surface Bindning Alters The Migatory Behavior Of Embryonic
Endocardial-Derived Mesenchymal
Cells In Vitro.
Development 118, 931-939.
Alexander, SM., Jackson, KJ., Bushnell, KM., and McGuire, PG. (1997).
The Spatial and Temporal Expression of the 72kDa Type IV Collagenase (MMP-2)
Correlates with Development
and Differentiation of Valves in the Embryonic Avian Heart.
Developmental Dynamics 209, 261-268.
Majka, SM., and McGuire, PG. (1997). Regulation of Urokinase Expression
in the Developing Avian Heart: A Role for the Ets-2 Transcription Factor.
Mechanisms of Development.
68,127-137.
Das, A., McLemore, A., Song, WS., and McGuire, PG., (1998). Retinal Neovascularization is Suppressed with a Matrix Metalloproteinase Inhibitor.
Archives of Ophthalmology. 117,
498-503.
Song, W., Majka, SM., and McGuire, PG. (1999). Hepatocyte Growth Factor
Expression in the Developing Myocardium: Evidence for a Role in the Regulation
of the Mesenchymal Cell Phenotype and Urokinase Expression..
Developmental Dynamics. 214, 92-100.
Das, A., McGuire, PG., Eriqat, C., Ober, RR., Dejuan, E., and Williams, G.
(1999). Human Neovascular Membranes Contain High Levels of Urokinase and
Metalloproteinase Enzymes.
Investigative Ophthalmology and Visual Science. 40, 809-813.
Robbins, JR., McGuire, PG., Wehler-Haller, B., and Rogers, SL. (1999).
Diminished Matrix Metalloproteinase 2 (MMP-2) in Ectomesenchyme-Derived Tissues
of the Patch Mutant Mouse:
Regulation of MMP-2 by PDGF and Effects on Mesenchymal Cell Migration.
Developmental Biology. 212, 255-263.
Song, W., and McGuire, P.G. Degradation of Type IV Collagen by Matrix Metalloproteinases is an Important Step in the Epithelial-Mesenchymal Transformation of the Endocardial Cushions. In Press. Developmental Biology. 227, 606-617
Majka, S.M., McGuire, P.G., Colombo, S.M., and Das, A. 2001. The Balance
Between Proteinases and Inhibitors in a Murine Model of Proliferative
Retinopathy.
Investigative Ophthalmology and Visual Science. 42:210-215.
Majka, S.M., McGuire, P.G. and Das, A. 2002. Regulation of Matrix
Metalloproteinase Expression by Tumor Necrosis Factor in a Murine Model of
Retinal Neovascularization.
Investigative
Ophthalmology and Visual Science. 43:260-266.
McGuire, P.G., Jones, T.R.,.Talarico, N., Warren, E. and Das, A. 2003.
The Urokinase/Urokinase Receptor System in Retinal Neovascularization:
Inhibition by Å6 Suggests A New Therapeutic Target.
Investigative
Ophthalmology and Visual Science. 44-2736-2742.
Das, A., Fanslow, W., Cerretti, D., Warren, E., Talarico, N., and McGuire, P.G. 2003Angiopoietin/Tek Interactions Regulate MMP-9 Expression and Retinal Neovascularization. Laboratory Investigation.83:1637-1645.
Das, A. and McGuire P.G. 2003. Retinal and Choroidal Angiogenesis: Pathophysiology and Strategies for Inhibition. Prog Retin Eye Res. Nov;22(6):721-48.
Das, A., Boyd, N., Jones, TR., Talarico, N., and McGuire, PG. 2004. A Peptide Inhibitor of the Urokinase/Urokinase Receptor System Inhibits Choroidal Neovascularization in a Mouse Model. Archives of Ophthalmology. 122:1844-1849.
Giebel, S.J., Menicucci,G., McGuire, P.G. and Das, A.2005. Matrix Metalloproteinases in Early Diabetic Retinopathy and Their Role in Alteration of the Blood-Retinal-Barrier. Laboratory Investigation. 85:597-607.
Das, A., McGuire, PG. 2005. Role of Urokinase Inhibitors in Choroidal Neovascularization. Seminars in Ophthalmology. 21: 23-27.
Das, A., McGuire, PG. 2006. Proteinases in Ocular Angiogenesis. In; Retinal and Choroidal Neovascularization. Ed. Penn, J., Kluwer/Springer Academic Publisher.
Colombo, ES., Menicucci, G., McGuire, P.G., and Das, A. 2007. Hepatocyte Growth Factor/Scatter Factor Promotes Retinal Angiogenesis Through Increased Urokinase Expression. Investigative Ophthalmology and Visual Science. 48:1793-1800.
Navaratna, D., McGuire, P.G., Menicucci, G., and Das, A. 2007. Proteolytic Degradation of VE-Cadherin Alters the Blood-Retinal Barrier in Diabetes. Diabetes. 56: 2380-2387.
Navaratna, D., Maestas, J., McGuire, P.G., and Das, A. 2008. Retinal Neovascularization is Suppressed with an Antagonist to VE-cadherin. Archive of Ophthalmology. 126(8): 1082-1088.
Navaratna, D., Menicucci, G., Maestas, J., Srinivasan, R., McGuire, P.G. and Das, A. 2008. A Peptide Inhibitor of the Urokinase/Urokinase Receptor System Inhibits Alteration of the Blood-Retinal-Barrier in Diabetes. FASEB Journal. 22:3310-3317.
