Research

Changes in the neural environment that alter the blood-brain barrier

Retinal Research: Our goal is to understand the underlying retinal changes that occur in a variety of eye diseases so that we may develop novel therapies to prevent or reverse loss of vision in humans. These diseases include diabetic retinopathy, retinal vein occlusion, retinopathy of prematurity and age-related macular degeneration. All of these diseases include a change in the retinal vasculature increasing the vessel permeability and, in some cases, leading to increased blood vessel growth. Further, these changes in retinal blood vessels are associated with loss of normal neural retinal function and loss of vision. The use of rodent animal models allow us to understand the disease process and to determine which therapies hold promise to prevent or reverse loss of retinal function. This research explores the intimate relationship between the blood vessels and neural tissue in the retina, referred to as the neurovascular unit. Support cells in the neurovascular unit, such as glial cells and pericytes, provide factors that induce the blood-brain and blood-retinal barrier. These factors are altered under disease conditions contributing to the disease process. Research methods in the Antonetti laboratory include the study of protein/protein interaction; study of protein and organelle dynamics using fluorescent based techniques, mutational analysis, primay cell culture and transgenic animals studied for visual loss and changes in retinal function. Current research focuses on understanding how phosphorylation of the tight junction protein contributes to control of blood vessel permeability and proliferation. We are also working to use endogenous barrier promoting factors such as norrin to restore the blood-retinal barrier in diabetic animals and preserve vision. 

Stroke Research: Our studies on the blood-retinal barrier have led to novel understanding of the tight junction complex. These findings have led to new studies and collaborations to explore the role of occludin in stroke. Research shows that occludin phosphorylation contributes a critical role in regulating the blood-brain barrier in stroke. Drugs that prevent this phosphorylation are now being explored as a new means to prevent bleeding for stroke patients given thrombolytic therapy.