Mara Lorenzi, M.D.
Molecular mechanisms underlying Diabetic Retinopathy
My lab has focused on investigating mechanisms for diabetic retinopathy, with emphasis on the molecular and cellular aspects of human diabetic retinopathy. We tested in vivo the concept of glucose toxicity that we had formulated using cultured endothelial cells, and observed that the effect of diabetes on the gene expression of retinal vascular cells is remarkably similar to the program induced by high glucose in vitro. By documenting in human diabetic retinal vessels accelerated apoptosis of microvascular cells, complement activation, and microthrombosis, we provided mechanisms for the “pericyte drop-out” and “acellular capillaries” that are the histological hallmarks of diabetic retinopathy. We uncovered that not only the vessels are affected by diabetes in the retina. Müller glial cells acquire early in the course of both human and experimental diabetes a reactive phenotype.
2. Dagher Z, Park YS, Asnaghi V, Hoehn T, Gerhardinger C, Lorenzi M: Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy. Diabetes 2004; 53:2404-2411
3. Sun W, Gerhardinger C, Dagher Z, Hoehn T, Lorenzi M: Aspirin at low-intermediate concentrations protects retinal vessels in experimental diabetic retinopathy through non-platelet-mediated effects. Diabetes 2005; 54:3418-3426.
4. Gerhardinger C, Dagher Z, Sebastiani P, Park Y-S, Lorenzi M: The transforming growth factor-β pathway is a common target of drugs that prevent experimental diabetic retinopathy. Diabetes 2009; 58:1659-1667. PMCID: PMC2699853
5. Lorenzi M, Feke GT, Pitler L, Berisha F, Kolodjaschna J, McMeel JW: Defective myogenic response to posture change in retinal vessels of well-controlled type 1 diabetic patients without retinopathy. Invest Ophthalmol Vis Sci 2010; 51:6770-6775.
6. Zerbini G, Maestroni A, Palini A, Tremolada G, Lattanzio R, Maestroni S, Pastore MR, Secchi A, Bonfanti R, Gerhardinger C, Lorenzi M: Endothelial progenitor cells carrying monocyte markers are selectively abnormal in type 1 diabetic patients with early retinopathy. Diabetes 2012; 61:908-914. PMCID: PMC3314367.