Chief, Ophthalmology
Professor of Ophthalmology &
Cell Biology & Physiology,
Director of Retina & Vitreous Service
Ophthalmology
MSC10-5610
Department of Surgery
1 University of New Mexico
Albuquerque, NM 87131
Phone: (505) 272-6120
Fax: (505) 272-6125
e-mail: adas@unm.edu
Major Research Interests
Angiogenesis; Pharmacological inhibition of Ocular Angiogenesis; Proteases in angiogenesis; Diabetic Retinopathy; Age-related Macular Degeneration; Vascular Cell Biology.
Angiogenesis or growth of new blood vessels occurs in a variety of ocular conditions including diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity (retinal neovascularization), and age-related macular degeneration (choroidal neovascularization). All these conditions result in intraocular hemorrhage, and are among the leading causes of visual loss today.
The initial stimulus for neovascularization (NV) is thought to be hypoxia, at least for retinal NV, that leads to production of several angiongenic factors including vascular endothelial growth factor (VEGF). VEGF seems to be the major mediator in new vessel formation.
A crucial event in the process of neovascularization is the remodeling and penetration of the capillary basement membrane by sprouting endothelial cells. This step requires tightly controlled degradation of specific components of the basement membrane and extracellular matrix by a variety of endothelium-derived proteolytic enzymes. Among the proteinases involved in the process of new vessel formation is the serine proteinase, urokinase, and members of the matrix metalloproteinase (MMP) family.
We have shown that the expression of urokinase, MMP-2 and MMP-9 is increased in retinas of an animal model of retinal NV. Systemic inhibition of MMPs with a synthetic MMP inhibitor, BB-94 can significantly suppress retinal NV by 72%, and thus may have therapeutic potential in preventing retinopathy associated with retinal NV. Also, similar inhibition of urokinase/urokinase receptor system with a novel peptide inhibitor, A6, can suppress retinal NV by 63%.
Currently, we are working on several proteases inhibitors in an animal model of choroidal neovascularization. With the inhibitor, A6, choroidal neovascularization can be suppressed by up to 94%. Such a pharmacological approach to intervene the pathway of angiogenesis may be an alternative therapeutic approach to wet macular degeneration.
Also, we are looking at the expression of proteases in early diabetic retinopathy, when the blood-retinal barrier is altered.
Education, Honors and Professional Experience
1980, M.D. University of Calcutta (India); 1983, M.S. (Ophthalmology), University of Calcutta; 1986, Ph.D. (Physiology), Medical College of Ohio, Toledo; 1986-1988, Research Associate, Wayne State University, Detroit; 1988-1989, Research Scientist, Kresge Eye Institute, W.S.U., Detroit; 1989-1992, Resident (Ophthalmology), Kresge Eye Institute, W.S.U., Detroit; 1992-1994, Vitreo-Retinal Fellow, Dohney Eye Institute, University of Southern California, Los Angeles; 1995-2001, Assistant Professor of Ophthalmology, University of New Mexico; 2001-present, Associate Professor of Ophthalmology and Cell Biology and Physiology, University of New Mexico; Director, Retina Service, Diplomat American Board of Ophthalmology.
Selected Recent Publications
Navaratna, D., Menicucucci, G, McGuire, P, Das, A. Increased proteinase activity leads to degradation of VE-cadherin resulting in alteration of the blood-retinal barrier in experimental diabetes. Diabetes 2007; 56:2380-87, 2007.
Colombo, ES, Menicucci G, Arup Das, McGuire, PG, Das, A. Hepatocyte Growth Factor/Scatter Factor Promotes Retinal Angiogenesis Through Increased Urokinase Expression, Invest Ophthalmol Vis Sci, 2007; 48:1793-800.
Lutty, GA, Chan-Ling, T, Phelps, D, Das, A et al. Proceedings of the Third International Symposium on Retinopathy of Prematurity: An update on ROP from the lab to the nursery. Mol Vis 2006; 12:532-580.
Campochiaro, P. and the First ARVO/Pfizer Ophthalmics Institute Working Group. Ocular vs. Extraocular Neovascularization: Mirror images or vague resemblances, Invest Ophthalmol Vis Sci 2006; 47:462-474.
Das, A. and McGuire, P.G. Role of urokinase inhibitors in choroidal neovascularization. Seminars in Ophthalmology. In Press, 2005.
Giebel, S., Menicucci, G., McGuire, P.G., Das, A; Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier. Lab Invest. 2005; 85:597-607.
Das, A., Boyd, N, Jones, T.R., Talarico, N., McGuire, P.G. A peptide inhibitor of the urokinase/urokinase receptor system inhibits choroidal neovascularization in a mouse model. Arch Ophthalmol 2004; 122:1844-49.
Das, A. Pathogenesis of Angiogenesis. Proceedings of 5th International Symposium of Ocular Pharmacology & Therapeutics, 2004, Medimond, Bologna, Italy.
Das A, McGuire PG. Retinal and choroidal angiogenesis: pathophysiology & strategies for inhibition. Progress in Retinal and Eye Research 2003; 22:721-748.
Das, A; Fanslow, W; Cerretti, D; Warren, E; Talarico, N; McGuire, P: Angiopoietin/Tek interactions regulate mmp-9 expression and retinal neovascularization; Lab Invest. 2003 Nov; 83(11): 1637-45.
McGuire, P., Jones, T.R., Talarico, N., Warren, E., Das, A.: The Urokinase/Urokinase Receptor System in Retinal Neovascularization: Inhibition by A6 Suggests a New Therapeutic Target; Invest. Ophthalmol. Vis. Sci. 2003 44: 2736-2742.
Majka, S., McGuire, P., Das, A.: Regulation of Matrix Metalloproteinase Expression by Tumor Necrosis Factor in a Murine Model of Retinal Neovascularization; Invest. Ophthalmol. Vis. Sci. 2002 43: 260-266.
Majka, S, McGuire, P., Colombo, S., Das, A.: The Balance between Proteinases and Inhibitors in a Murine Model of Proliferative Retinopathy; Invest. Ophthalmol. Vis. Sci. 2001 42: 210-215.
Das, A., McGuire, P., Eriqat, C., Ober, R.R., Dejuan E., Williams, G.A., McLamore, A., Biswas, J., Johnson, D.W.: Human Diabetic Neovascular Membranes Contain High Levels of Urokinase and Metalloproteinase Enzymes; Invest. Ophthalmol. Vis. Sci. 1999 40: 809-813.
Das, A., McLamore, A., Song, W., and McGuire, P.: Retinal Neovascularization is Suppressed with a Matrix Metalloproteinase inhibitor; Arch. Ophthalmol. 1999: 117: 498-503.
Selected Book Chapters
Biswas J. and Das A. Pathogenesis and Pathology of Diabetic Retinopathy, In Diabetic Retinopathy for the Clinician, Ed Abrahams, C. Jaypee Brothers, Medical Publishers, New Delhi, 2007 (In Press).
Das, A, Navaratna, D, McGuire P. “Beyond VEGF – Other Potential molecules involved in retinal neovascularization ” in Diabetic Retinopathy, ed. Duh, E, Humana Press, Totowa, NJ, 2007, (In Press).
Das, A. and McGuire, P.: “Proteinases in Ocular Angiogenesis”, in Retinal and Choroidal Neovascularization, ed. Penn, J., Kluwer/Springer Academic Publisher, 2005.
Das, A. and Frambach, D.: “Branch Retinal Vein Occlusion” in Medical and Surgical Retina – Advances, Controversies, and Management, ed. Lewis, H. and Ryan, S.J., C.V. Mosby Co., p. 374-381, 1993.
Frank, R.N. and Das, A.: “Pathogenic mechanisms in Diabetic Eye Diseases” in Ocular Problems in Diabetes Mellitus, ed. Feman, S.S., Blackwell Scientific Publications, Oxford, U.I., p. 95-133, 1991.
Current Research Support
Principal Investigator: Juvenile Diabetes Research Foundation, “Extracellular Proteinases in Early Diabetic Retinopathy”, 5/1/2006-4/30/2009.
Principal Investigation: NIH R01 12604-08, “Proteinases in Ocular Neovascularization”, National Eye Institute, NIH, 07/01/2006-6/30/2011.
P.I. Juvenile Diabetes Research Foundation, Ranibizumab for Edema of the Macula in Diabetes: A Phase 2 Study (READ-2), (multi-centered clinical trial), 11/1/2006-10/1/2008.
P.I. Genentech, Ranibizumab in Diabetic Edema (RIDE): A Phase III multi-centered clinical trial, 7/1/2007-6/30/2010.
Co-PI. American diabetes Association. Role of HGF in Retinal Angiogensis. 07/01/2004-2007.
Honors, Activities, etc.
Memberships In Professional Societies
