Our lab is interested in the molecular mechanisms whereby neuronal cells are protected from ischemic injury.
Studies involve a combination of sophisticated functional studies of the intact retina, light microscopic and electron microscopic examination, as well as immunostaining, and standard molecular biological tools, and pharmacological activators and inhibitors, interfering RNA, and viral vectors. We use in vivo rat retina for our studies.
The work originated with our demonstration that a brief, non-damaging ischemic insult to the rat retina resulted in profound neuroprotection when the retina was subjected to severe ischemia, reflected both by preservation of function as well as prevention of histological damage.
We then began to explore the mechanisms, demonstrating the involvement of a series of cellular signaling steps including activation of adenosine receptors, mitochondrial kATP channels, specific subtypes of protein kinase C, and an inhibition of apoptotic injury. Subsequent studies in recent years have shown the involvement of mitogen activated protein kinase p38, Akt (protein kinase B), and the cytokine erythropoietin.
Our current studies are focused on determination of the mechanisms downstream from these mediators. We also have shown that this neuroprotection by brief ischemia can also be induced when it is carried out up to 24 h after ischemia. This intriguing phenomenon is known as post-ischemic conditioning. Currently we are studying its mechanisms.
In other studies, we have determined that bone marrow stem cells as well as conditioned media can also mimic the effects of post conditioning, and mechanisms of these effects are being studied.
The ultimate goal of this research is to better understand the retina's endogenous protective mechanisms with a goal of developing rational therapeutic strategies. These studies are relevant to acute retinal ischemia and to chronic diseases that lead to blindness including diabetic retinopathy.
The research in the lab is currently supported by: * The National Institutes of Health (EY10343-18) * The Glaucoma Foundation * The University of Chicago Institute for Translational Medicine * The Chicago and France Collaborating in the Sciences
Dreixler JC, Poston JN, Shaikh AR, Alexander MJ, Tupper KY, Marcet MM, Bernaudin M, Roth S: Delayed post-conditioning significantly improves outcome after retinal ischemia in rats. Experimental Eye Research 92: 521-527, 2011
David J, Melamud A, Kesner L, Roth S, Rosenbaum PS, Barone FC, Popp S, Hassen GW, Stracher A, Rosenbaum DM. A novel calpain inhibitor for the treatment of transient retinal ischemia in the rat. Neuroreport 22: 633-636, 2011.
Dreixler JC, Shaikh AR, Alexander M, Savoie. B, Roth S: Postischemic conditioning in the rat retina is dependent upon ischemia duration and is not additive with ischemic preconditioning. Experimental Eye Research 91: 844-852, 2010.
Savitz SI, Degterov A, David J, Rosenbaum PS, Roth S, Grotta JC, Cuny GD, Yuan J, Rosenbaum DM: Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model. Journal of Neuroscience Methods 88: 1569-76, 2010
Find us: Room I-423, Brain-surgery Building on Ellis, University of Chicago Medical Center