Patrice E. Fort, PhD, MS
Inflammation is increasingly recognized as a major player in the pathophysiological mechanisms of diabetic retinopathy. Through our discovery approaches performed on ocular tissues from human donors with and without diabetes and/or retinopathy, several inflammatory regulators have been identified and are currently under investigation.
Additionally, alpha-crystallins have been associated with inflammation in multiple sclerosis and other neuro-inflammatory associated diseases, but the potential interaction in diabetic retinopathy has not been explored. We are exploring the role of alpha-crystallins in the regulation of the retinal inflammatory response using cell culture methods as well as animal models of neuro-infllammatory diseases.
Thomas Wubben, MD, PhD
Targeting metabolism as a therapeutic for proliferative vitreoretinopathy (PVR)
Retinal detachment (RD) is an important cause of visual loss and its incidence is increasing. Proliferative vitreoretinopathy (PVR), which is characterized by fibrotic membranes on both surfaces of the retina, represents the greatest risk of failure of RD repair surgery and portends poor visual outcomes. PVR management is currently restricted to the surgical removal of the membranes, which can incite further retinal damage and recurrent PVR. As no pharmacologic intervention has prevented the formation of PVR, a significant unmet therapeutic need exists. Yet, limited understanding of PVR’s molecular mechanisms has hampered development of such therapeutics. This project provides fundamental insight into the cellular metabolic reprogramming that is crucial in the pathogenesis of PVR.
PVR is a complex process that involves the coordination of retinal pigment epithelium (RPE), glia, macrophages, and T cells. As metabolic reprogramming regulates the activation of T cells and macrophages and the fibroblastic transition RPE cells undergo during this visually debilitating process, targeting metabolism may be a novel therapeutic strategy that affects two critical components in PVR pathogenesis.