Head: Lloyd Paul Aiello, MD, PhD

To determine how to prevent and treat eye complications of diabetes

The major goal of these laboratories is to elucidate the molecular, physiologic and biologic mechanisms underlying the onset and development of diabetic retinopathy, diabetic macular edema and visual loss from diabetes. These efforts span the full bench-to-bedside effort. Initial mechanistic studies utilize molecular biology and retinal cells. The effects are then evaluated in animal models for proof of mechanistic importance and in assessing potential novel interventions. Many of the assays used in the animals are also applicable to human patients. Human and retinal hemodynamics and physiology can be studied in parallel. Thus, when appropriate, the studies can be evaluated in clinical trials. The Section on Eye Research has been active in the conceptualization, design and implementation of all phases of human clinical trials. In close association with the Section on Vascular Cell Biology, we have guided initial biochemical studies through this entire process to current FDA consideration of a novel oral therapy (PKC-β inhibitor, ruboxistaurin) for regulatory approval for treatment of visual loss in diabetes.

Aiello Lab:

Major research interests in this laboratory have focused on the molecular biology of ischemic retinal disease, growth factor mediation of proliferative retinopathies and macular edema, proteomic characterization of the retinopathy process in humans, hypertension interactions with retinal disease, clinical trial design and implementation as applied to diabetic retinopathy, macular edema and retinal vascular disorders. The research is focused on understanding basic molecular biological mechanisms underlying retinal vascular disease with emphasis on the activity of growth factors in diabetic retinopathy and macular edema. The mechanistic details are utilized as the foundation from which to target and design novel interventional approaches and subsequently to design and pursue animal and human clinical trials. Ongoing clinical studies include effects of oral protein kinase C inhibitors, growth factor inhibitors, antioxidants, anti-proliferative agents and the genetics and proteomics of diabetic eye disease.

Bursell Lab:

Research has centered on the cellular mechanisms and hemodynamic processes that contribute to diabetic retinopathy. An understanding of these mechanisms and their importance at various periods of the disease process has enhanced the ability to predict, at the earliest stages, the risk for developing diabetic ocular complications and has helped facilitate the development of therapeutic agents to prevent or ameliorate the progression of diabetic retinopathy and associated vision loss. Work focuses on the characterization of retinal neuronal (scotopic ERG) and vascular (retinal blood flow & permeability) function in the PKC-β over-expression and knockout mouse models, endothelial dysfunction in insulin resistance versus diabetic states, development of novel retinal imaging techniques and targets, and the identification of a biochemical trigger between retinal vascular permeability and intra-retinal edema in diabetes.

Five recent “highpoints”: