Evan B. Stubbs, Jr, PhD

Professor and Vice Chair of Research of Ophthalmology

Research Health Scientist, Edward Hines Jr. VA Hospital

Education

B.S., Chemistry, University of Illinois, Urbana-Champaign
Ph.D., Biochemistry, University of Missouri, Columbia
Postdoctoral Fellowship, Neurochemistry, University of Michigan, Ann Arbor

Research Interests

Glaucomatous Neuropathy

Historical Background: Primary open-angle glaucoma (POAG) is a slowly progressive irreversible optic neuropathy with characteristic optic nerve degeneration and progressive visual field loss. The prevalence of POAG in the US population 40 years and older is approximately 1.86% or nearly 2 million individuals. Over 60 million cases of blindness can be attributed to glaucoma worldwide. The personal, social, and medical burden of this disease is experienced globally and remains a significant concern. Studies designed to treat POAG are extremely important and are currently under-represented.

Central Findings and Relevance to Health: Findings from my lab have established that elevated levels of TGF- β2 present in AH of POAG patients elevate intraocular pressure, in part, by eliciting aberrant Rho GTPase dependent cell contraction, and increasing ET-1 synthesis and secretion, in human TM cells. These findings offer much needed new and novel therapeutic strategies for the management of patients with POAG.

Immune-Mediated Peripheral Neuropathy

Historical Background: These neuropathies are rare but potentially catastrophic autoimmune disorders that are clinically heterogeneous with known or suspected infectious etiologies. Included among these disabling disorders is acute inflammatory demyelinating polyradiculopathy (AIDP), a common North American and European variant of Guillain-Barré Syndrome (GBS). In the US, thousands of GBS cases are reported annually with an overall yearly social and economic burden exceeding an estimated $1.8 billion. Subsequent to the virtual eradication of poliomyelitis, GBS is now considered the leading cause of acute flaccid paralysis in Western countries. GBS occurs with an incidence rate of 0.2-4.0 cases per 100,000, a frequency that is alarmingly similar to that reported for multiple sclerosis.

Central Findings and Relevance to Health: Findings from my lab show that a short-term application of high- dose statins or novel prenyltransferase inhibitors may prove clinically useful in the management of inflammatory demyelinating peripheral nerve diseases, including some clinical sub-groups of Guillain-Barré syndrome, by limiting transendothelial migration of autoreactive leukocytes. Recent advancements include the application of PLGA nanoparticles as a novel therapeutic strategy for the management of AIDP. These findings offer new hope for the development of improved therapeutic strategies for the treatment and management of these potentially devastating disorders of the peripheral nerves.

Diabetic Neuropathy

Historical Background: Diabetes mellitus (diabetes) is the most common cause of blindness, end-stage renal disease, and non-traumatic lower extremity limb amputations in adults. Whether insulin-dependent (type 1) or non-insulin dependent (type 2), diabetes is defined as a metabolic, rather than an immune-mediated, disorder complicated by long-term microvascular, neurologic, and macrovascular complications. Type 2 diabetes has reached epidemic proportions in the United States, affecting more than 26 million Americans, or greater than 8% of the population. Obesity, secondary to physical inactivity, is cited as a major factor in the increasing rates of type 2 diabetes. Greater than half of all patients with diabetes develop polyneuropathy, a debilitating progressive deterioration of peripheral and autonomic nerves. Vascular dysfunction, leading to reduced nerve blood flow and reduced endoneurial oxygen tension, is considered a primary contributor to diabetic polyneuropathy. Currently, diabetic polyneuropathy is untreatable in humans. Innovative treatment strategies designed to address pre- existing nerve injury in the aged diabetic patient are critically needed.

Central Findings and Relevance to Health: We have just concluded a single-site clinical study evaluating the effectiveness of aerobic/strength training exercise on progression of peripheral neuropathy in type 2 diabetic Veterans with length-dependent sensory polyneuropathy. Our preliminary findings show moderate intensity aerobic exercise produces measurable, and in some cases significant (p<0.03), improvement over baseline in motor and sensory nerve conduction electrodiagnostic primary outcome studies. Pre-clinical evaluation of this therapeutic intervention showed that forced exercise markedly delays the onset of diabetes associated neuropathic pain, in part, by enhancing opioid mediated attenuation of high- and low voltage-activated Ca²⁺ channel function within small-diameter (nociceptive) DRG neurons. We postulate that recovery of peripheral nerve function in both humans and experimental animals occurs by neuroplastic remodeling (growth of new nerve fibers) secondary to exercise-improved tissue oxygenation.

Publications/Research Listings