Mara Lorenzi,
M.D.
Professor of Ophthalmology
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This program comprises several projects aiming to reconstruct the cellular and molecular events that underlie the well-known histological lesions of nonproliferative diabetic retinopathy. The work focuses currently on the events leading to microvascular obliteration, the main cause of retinal ischemia and neovascularization in diabetes. Recent studies have identified processes that may be operative in the causation of microvascular occlusion and obliteration in the diabetic retina: apoptosis of endothelial cells and pericytes, microthrombosis, and complement activation. In addition, we have uncovered that also glial cells of the retina are affected by diabetes, and show signs of activation. Four bench projects address these processes and their relationships: (1) Definition of the mechanisms and consequences of the complement activation occurring in retinal vessels; (2) Regulation of intracellular modulators of apoptosis in diabetes, and investigation of their role in causing the apoptosis of retinal microvascular cells; (3) Definition of the mechanisms underlying activation of Muller glial cells and (4) Evaluation of single or combined pharmacological interventions on the gene expression profile of the diabetic retina and retinal vascular cells, and the development of retinopathy. The experimental approaches include studies in retinas and retinal microvessels isolated from diabetic patients and animal models of diabetic retinopathy, and the use of knock-out animals and cultured cells to define the role of candidate abnormalities. In addition, a recently initiated clinical project aims at determining whether microthrombosis is an early event in the retina of patients with type 1 diabetes. Each project is articulated in subprojects among which trainees can identify the one best fitting their background and interests. The ultimate goal is to define the pathogenic contribution of discrete biochemical pathways or molecular processes that can become rational targets for intervention, and begin to assess the possible value of available drugs.
Selected Publications:
Mizutani M, Kern TS, Lorenzi M. Accelerated death of retinal microvascular cells in human and experimental diabetic retinopathy. J Clin Invest 97:2883-2890,1996.
Boeri D, Maiello M, Lorenzi M. Increased prevalence of microthromboses in retinal capillaries of diabetic individuals. Diabetes 50: 1432-1439,2001
Zhang J, Gerhardinger C, Lorenzi M: Early complement activation and decreased levels of glycosylphosphatidylinositol-anchored complement inhibitors in human and experimental diabetic retinopathy. Diabetes 51:3499-3504,2002
Asnaghi V, Gerhardinger C, Hoehn T, Adeboje A, Lorenzi M: A Role for the Polyol Pathway in the Early Neuroretinal Apoptosis and Glial Changes Induced by Diabetes in the Rat. Diabetes 52:506-511,2003
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