Ernest C. Steele, Jr.
Assistant Professor
e-mail: esteele@msm.edu
B.S., Biology, Emory College,
Atlanta, GA
Ph.D., Genetics and Molecular Biology Program, Graduate Division of Biological and Biomedical Sciences, Graduate School of Arts and Sciences, Emory University
Non age-related loss of vision results in a significant reduction in the quality of life for countless individuals and represents a large economic burden on societies around the world. Blindness can occur due to hereditary mutations in specific genes or result from a plethora of acute environmental insults or even from complex interactions between genes and the contextual environment of an individual. Since his initial studies of the molecular and genetic basis of cataracts as a graduate student under the direction of Dr. Robert L. Church , Dr. Steele has been committed to expanding our understanding of the underlying cellular and molecular basis of vision loss as the critical and necessary first step toward the development of effective intervention and prevention strategies to reduce the burden of blindness on society.
Over the last few years, Dr. Steele has focused his scientific attention, under the tutelage of Dr. Peter R. MacLeish, to the study of various aspects of retinal anatomy and physiology and their relevance to both normal and pathologic retinal functioning. Early studies with Dr. MacLeish employed electrophysiology and ratiometric calcium imaging methods to record and correlate whole cell ionic currents and intracellular calcium dynamics within the subcellular compartments of acutely isolated fully intact rod photoreceptors.
Dr. Steele has most recently initiated a new independently funded line of research exploring the potential contribution of acute changes in the expression, localization, or functional profiles of P2X and P2Y purinergic receptors in retinal macroglial Müller during the early stages of development and progression of diabetic retinopathy. These studies will employ an array of molecular techniques including RT-PCR, in situ hybridization, immunohistochemistry, and Western blot in conjunction with ratiometric calcium imaging and electrophysiology to examine parallel changes in in vivo (streptozotocin-induced diabetic rats) and in vitro (immortalized rat Müller cell cultures) models. These studies promise to establish the Müller cell as a novel cellular target and the purinergic receptors and associated pathways as novel molecular targets for the development of earlier intervention and/or prevention strategies to ameliorate or prevent the blinding complication of diabetic retinopathy in diabetic patients. Furthermore, these studies will establish the usefulness of the immortalized Müller cell culture model as a more rapid and inexpensive means of testing the efficacy of various therapeutic reagents and strategies to ameliorate or prevent these Müller cell changes.
In collaboration with the laboratory of Dr. Shobu Namura, Dr. Steele has also recently established that the middle cerebral artery occlusion (MCAO) paradigm, classically used by stroke researchers to produce and study transient unilateral focal strokes in the brain, also reproducibly produces profound unilateral damage in the retinas of mice. This model should more faithfully recapitulate the ischemic damage and loss of vision that is often associated with embolic and thrombotic stroke and allow for comparison and contrast of the molecular details of etiology with those of high pressure-mediated ischemia associated with glaucoma or ischemic damage associated with diabetic retinopathy. This model will also provide the opportunity to directly compare mechanistic details of ischemic damage and the efficacy of therapeutic strategies to ameliorate or prevent this damage in two distinct CNS tissues with internal controls within the same animals. Dr. Steele is particularly interested in studying the potential contribution of acute ischemia and hypoxia-induced changes in retinal Müller cell expression and functional profiles to the development and progression of retinopathy in the MCAO model.
It is Dr. Steele’s hope that his ongoing basic research regarding the expression and function of Müller cells in both normal and pathologic retina will one day translate into effective therapies for earlier intervention and prevention of the blinding complications of conditions such as diabetes and stroke.
