More than 25 scientists from Schepens Eye Research Institute will present their research at the Annual Meeting of ARVO. One is titled New Drug Traps Growth Factor that Causes Abnormal Blood and Lymphatic Vessels in Corneas, and the other is Gene Therapy to Produce a-MSH Promises to Prevent and Treat Autoimmune Uveitis and Other Autoimmune Diseases. (Meeting: American Association for Research in Vision and Opthalmology)
Schepens Eye Research Institute
More than 25 scientists from Schepens Eye Research Institute will present their research at the Annual Meeting of ARVO, the American Association for Research in Vision and Opthalmology in Fort Lauderdale from May 5 to May 8. Here are two hightlights from those presentations.
New Drug Traps Growth Factor that Causes Abnormal Blood and Lymphatic Vessels in Corneas *
Dr. Claus Cursiefen and Dr. J. Wayne Streilein will present the results of a study in which they found that a drug, known as the Vascular Endothelial Growth Factor Trap, could block the abnormal growth of corneal blood and lymphatic vessels that accompany certain types of corneal diseases (in this case, inflammatory corneal diseases such as herpetic keratitis). Their study also demonstrated that this new drug might ultimately prevent the rapid rejection of transplanted corneal tissue in the eyes of individuals with these diseases.
The normal cornea, which is the window of the eye, is free of both blood and lymphatic vessels to achieve maximal clarity for light entering the eye and, therefore, good vision. When these vessels do grow in the cornea in diseases such as herpetic keratitis, the only option has been to transplant a clear new donor cornea into the center of the patient's cornea. Unfortunately, preexisting blood vessels within the patient's remaining cornea make such a corneal transplantation a high-risk operation, often causing rejection despite conventional drug treatment.
Using a mouse model previously developed at Schepens Eye Research Institute, the researchers found not only the easily detectable blood vessels, but also lymphatic vessels, which had been previously difficult to detect. They also found for the first time that lymphatic vessels enter the cornea astonishingly quickly and in parallel with the blood vessels, after corneal inflammation begins. In addition, they demonstrated that the growth factors which cause lymphangiogenesis in tumors (VEGF C, D, A) are also increased in the cornea with developing angiogenesis (outgrowth of new blood vessels). Finally they showed that by using Regeneron's VEGF Trap, which acts like a "sink" and "traps" the angiogenic VEGF growth factor, they could completely inhibit both types of vessel growth in the mouse model.
Gene Therapy to Produce a-MSH Promises to Prevent and Treat Autoimmune Uveitis and Other Autoimmune Diseases**
Dr. Daniel Biros and Dr. Andrew Taylor will present results of a study that shows that gene therapy used to produce a protein called a-MSH (alpha-melanocyte stimulating hormone) holds promise for the treatment of autoimmune uveitis, a disease that causes permanent retinal damage and blindness. Previously, Biros and Taylor reported on the ability of intravenous injections of a-MSH itself to suppress uveitis, They have also demonstrated that a-MSH induces the body's production of a special type of T cell that works to further diminish the harmful effects of autoimmune disease.
When mice with uveitis were injected with a gene that codes for (or causes the production of) a-MSH, there were significantly fewer mice that expressed retinal inflammation (40 - 50% incidence) in contrast to untreated eyes (80 - 100% incidence). Eyes injected with a-MSH protein itself also had significantly less inflammation compared to untreated eyes. Biros and Taylor also found that the gene therapy was more effective than cytokine (protein) therapy. Microscopic examination of the retinas from inflamed eyes treated by gene therapy for a-MSH displayed normal, healthy structures unlike the untreated eyes where the retinal tissues displayed damage, cell loss, and disorganization.
The researchers believe that treatment with a-MSH not only can decrease the risk of severe retinal damage during the course of autoimmune eye disease, but also has great potential to suppress inflammation and protect delicate tissues affected in other autoimmune diseases, such as multiple sclerosis and type I diabetes.
Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the world.
*"Complete Inhibition of Simultaneous Onset Corneal Lymphangiogenesis and Angiogenesis by Trapping Vascular Endothelial Growth Factor (VEGF) Using a VEGF Receptor 1 and 2 Chimeric Protein (VEGF TrapR1R))
(Wednesday, 11:45 a.m. - 12:00 p.m.) C.Cursiefen1, L.Chen1, D.Jackson2, J.Rudge3, S.Wiegand3, R.Dana1, W.Streilein1. 1Dept. of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, Boston, MA; 2Institute of Molecular Medicine Oxford, MRC Human Immunology Unit, Oxford, United Kingdom; 3Regeneron Pharmaceuticals Inc., Tarrytown, NJ.
**"Suppression of Experimental Autoimmune Uveitis Using a Plasmid Encoding
the Ocular Immunosuppressive Cytokine Alpha-Melanocyte Stimulating Hormone"
(Thursday, 5:00 p.m. - 5:15 p.m.)
D.J. Biros, A.W. Taylor. Schepens Eye Research Institute and the Department
of Ophthalmology, Harvard Medical School, Boston, MA.
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