Sayon Roy, PhD, FARVO
PROFESSOR OF MEDICINE AND OPHTHALMOLOGY
- Laboratory: 617-638-4107
- Office: 617-638-4110
B.S. and M.S. University of Kalyani, India
Ph.D. Boston University/Harvard Medical School
Department of Ophthalmology, Harvard Medical School, Boston
Vascular basement membrane thickening is a prominent and characteristic lesion of diabetic retinopathy. We have hypothesized that excess synthesis of basement membrane components occurring in diabetes is a critical pathogenetic event in the development of vascular basement membrane thickening and complications of diabetic retinopathy. Having shown that the mRNA level of basement membrane components fibronectin and collagen IV are increased in diabetic retinas, our laboratory plans to reduce the synthesis of these basement membrane components by using antisense oligonucleotides, a powerful molecular biological tool that offers a unique opportunity to down regulate specific gene expression.
Experiments performed with antisense oligonucleotides in our laboratory have shown reduction of fibronectin mRNA and protein level by nearly 50% in cultured endothelial cells exposed to high glucose. Recently we have developed a strategy for in vivo application of antisense oligonucleotide and tested its applicability towards reduction of specific gene expression in retinal vascular cells. Following intravitreal delivery of antisense oligonucleotides we have reduced fibronectin overexpression in the diabetic rat retina that reduced significant retinal vascular cell loss associated with the development of diabetic retinopathy.
Another project in our laboratory, aims at understanding how retinal vascular homeostasis is disrupted by diabetes. In this project we are currently investigating whether high glucose alters the expression of endothelial specific connexins (gap junction proteins) (Cx37, Cx40, Cx43), and connexin phosphorylation pattern. In a different project, we are studying mechanism(s) on how diabetes might alter expression of the tight junction proteins leading to blood retinal barrier (BRB) breakdown in diabetic retinopathy.
We are investigating a potential biochemical link between the pathogenesis of diabetic retinopathy and glaucoma by examining the consequence of high glucose-induced overexpression of ECM proteins in trabecular meshwork cells and Schlemm’s canal cells and its potential role in the development of outflow resistance.
Li AF, Tane N, Roy S. Fibronectin overexpression inhibits trabecular meshwork cell monolayer permeability. Mol Vis. 10:750-7, 2004.
Oshitari T, Brown D, and Roy S. SiRNA strategy against overexpression of extracellular matrix in diabetic retinopathy. Exp Eye Res 81:32-37, 2005.
Oshitari T and Roy S. Diabetes: A potential enhancer of retinal injury in rat retinas. Neuroscience Letters, 390:25-30, 2005.
Oshitari T, Polewski P, Chadda M, Li AF, Sato T, Roy S. Effect of combined AS-oligos against high glucose- and diabetes-induced overexpression of extracellular matrix components and increased vascular permeability. Diabetes 55:86-92, 2006.
Oshitari T, Fujimoto N, Hanawa K, Adachi-Usami E, Roy S. Effect of chronic hyperglycemia on intraocular pressure in patients with diabetes. Am J Ophthalmol 143(2):363-5, 2007.
Tane N, Dhar S, Roy S, Pinheiro A, Ohira A, Roy, S. Effect of excess synthesis of extracellular matrix components by trabecular meshwork cells: possible consequence on aqueous outflow. Exp Eye Res 84(5):832-842, 2007.
Oshitari T and Roy S. Common therapeutic strategies for diabetic retinopathy and glaucoma. Current Drug Therapy 2(3): 224-232, 2007.
Behl Y, Krothapalli P, Desta T, DiPiazza A, Roy S, Graves DT. Diabetes-enhanced TNF-a Production Promotes Apoptosis and the Loss of Retinal Microvacular Cells in Type 1 and Type 2 Models of Diabetic Retinopathy. Am J Pathol, 172:1411-1418, 2008.
Oshitari T, Yamamoto S, Hata N, Roy S. Mitochondria- and caspase-dependent cell death pathway involved in neuronal degeneration in diabetic retinopathy. British J of Ophthalmology, 92:552-556, 2008.
Cherian S, Roy A, Pinheiro A, Roy S. Tight glycemic control reduces fibronectin overexpression and basement membrane thickening in retinal and glomerular capillaries of diabetic rats. Invest Ophthalmol Vis Sci, 50:943-949, 2009.
Behl Y, Krothapalli P, Desta T, Roy S, Graves DT. FOXO1 Plays an Important Role in Enhanced Microvascular Cell Apoptosis and Microvascular Cell Loss in Type 1 and Type 2 Diabetic Rats. Diabetes, 58(4):917-925, 2009.
Li AF, Roy S. High Glucose-induced Downregulation of Connexin 43 Expression Promotes Apoptosis in Microvascular Endothelial Cells. Invest Ophthalmol Vis Sci, 50:1400-1407, 2009.
Alikahani M, Roy S, and Graves DT. FOXO1 Plays an Essential Role in Apoptosis of Retinal Pericytes. Molecular Vision 2009 (In Press).