Bringing insight to vision science

Our lab is interested in the molecular mechanisms whereby neuronal cells are protected from ischemic injury.

Research

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

Previous recent support has come from, among others: * The North American Neuro-ophthalmological Society * The Brain Research Foundation

People

Dr. Roth is the PI. He is a Professor with Tenure, and Chief of Neuroanesthesia in the Department of Anesthesia and Critical Care, a member of the Committee on Neurobiology, and the Committee on Molecular Medicine. More biographical information is here.

John Dreixler, PhD, a Chicago native, is a Research Associate. A highly trained molecular neurobiologist, John has been responsible for development of the most complex tasks and methods that we use in the lab, and has been first author on numerous publications coming out of the lab.

A highly experienced technician, Shaikh is involved in every aspect of the projects in the lab.

Sineadh Conway, BS, a Chicago native, is a recent graduate of Arizona State University’s Honors College, a Research Technician, and a new addition to the lab. She is largely involved in imaging and running the complex analysis scheme for studying visual neurophysiology, but is quickly becoming skilled in every other aspect of the lab.

Isaac Parakati is a fourth year undergraduate at the College of the University of Chicago. Isaac spent two summers in the lab and manages to work part time during the very demanding school year at the University. Besides developing expertise in data analysis, Isaac’s imprint can be seen very clearly on this website.

Publications

Lee LA, Roth S, Todd MT, Posner KL, Polissar NL, Neradilek MB, et al. Risk factors associated with ischemic optic neuropathy after spinal fusion surgery. Anesthesiology 116:15-24, 2012

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

Dreixler JC, Sampat A, Shaikh AR, Marcet MM, Roth S: Akt and MAPK p38 in retinal ischemic postconditioning. Journal of Molecular Neuroscience 45:309-20, 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, Bratton A, Du E, Shaikh AR, Marcet M, Roth S: Mitogen activated protein kinase phosphatase-1 (MKP-1) in retinal ischemic preconditioning. Experimental Eye Research 93:340-9, 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

Dreixler JC, Shaikh AR, Savoie B, Du E, Roth S: p38 alpha in retinal ischemic preconditioning. Experimental Eye Research 88:512-21, 2009

Dreixler JC, Hagevik S, Hemmert JW, Shaikh AR, Rosenbaum DM, Roth S: Involvement of erythropoietin in retinal ischemic preconditioning. Anesthesiology 110:774-780, 2009.

Shen Y, Drum M, Roth S: Prevalence of preoperative visual loss in the United States: A study of general, cardiac, and spine surgery. Anesthesia and Analgesia, 109:1534-1545, 2009

Dreixler JC, Hemmert JW, Shenoy SS, Shen Y, Lee HT, Shaikh AR, Rosenbaum DM, Roth S: Akt/Protein kinase B subtypes and retinal ischemic preconditioning. Experimental Eye Research 88:512-521, 2009

Find us: Room I-423, Brain-surgery Building on Ellis, University of Chicago Medical Center

Phone: 773-834-9081