Michael Grassi, MD

My laboratory works specifically toward improving our current understanding of the molecular basis of diabetic retinopathy. We employ a multi-faceted and interdisciplinary approach to address this problem. Through my clinical practice we are assembling a large cohort of well-characterized patients with diabetic retinopathy. We are working towards identifying those genetic factors that predispose to this condition using techniques such as linkage analysis, candidate gene screening, and association studies. We are presently analyzing a large cohort of patients with diabetes who have already been genotyped at over 500,000 markers known as single nucleotide polymorphisms. We are characterizing the ocular phenotype of these individuals so that we may identify those genes associated with diabetic retinopathy severity. Such genetic information will become critical in identifying individuals at high-risk for the blinding complications of diabetic retinopathy who warrant treatment with prophylactic therapies. We have incorporated bioinformatic modeling to predict and associate other molecules important in the pathogenesis of diabetic retinopathy in part by examining pathways implicated by mendelian diseases that recapitulate some of features of diabetic retinopathy. We are currently using an immortalized retinal endothelial cell culture line (TR-iBRB) to explore the interaction and relevance of these molecules to diabetic retinopathy pathogenesis. The cell line will also allow us to follow-up on positive associations in our genetic studies through the use of molecular biologic approaches. This research is poised to provide new genetic and molecular insights into diabetic retinopathy and potentially hasten a more effective treatment or means of prevention.

Figure 1. Characterization of TR-iBRB tube formation in Matrigel. TR-iBRB retinal microvascular endothelial cells grown in Matrigel were fixed with 5% formalin and stained with ß-catenin (d, green), and F-actin (e, red) antibodies and nuclei stained with DAPI (c, blue). a: Bright field image; b: Merged image.

Figure 2. TR-iBRB tube formation in Matrigel. TR-iBRB retinal microvascular endothelial cells grown in Matrigel were imaged on d7 by confocal microscopy. Serial z- stack images were taken at 1 um step size. This is section 55 of the z-stack, a representation of the TR-iBRB in 3-D culture.