Neurology; Ophthalmology; Neuroophthalmology
I am a neuro-ophthalmologist with a primary clinical interest in optic neuropathy and vasculitis. I see a full range of neuro-ophthalmologic conditions, but I specialize in adult autoimmune optic neuropathy syndromes, diplopia, headache and multiple sclerosis (MS). I am also a board-certified ophthalmologist and conduct vision tests such as visual field testing, ocular coherence tomography (this assesses the health of the retina and optic nerve), sensorimotor examination and prism measurements. I see patients five days a week at UBMD Neurology at Buffalo General Medical Center. My main research interests include preventative treatment trials for autoimmune optic neuropathies and neuroprotection. I present annually at national and international conferences regarding MS and the use of ocular coherence tomography and imaging in my field. I am also involved in the “Hopeful Ways Nicaragua Eye Care Mission Project,” an annual medical mission to Nicaragua to prevent blindness. I work together with a group of medical professionals, local interpreters and Peace Corps volunteers to provide free vision care to over 2,600 patients a year. I am actively involved in training medical students, residents and fellows. I lecture weekly to students in small group sessions as well as larger lecture settings at UB.
Cornea & External Disease; Ophthalmology; Vision science
As a specialist in cornea and external diseases of the eye, I treat a wide range of eye problems and perform a variety of surgical procedures including corneal transplantation, cataract surgery, conjunctival tumor surgery, and transplantation of the artificial cornea when standard corneal transplantation has failed. One of the most common reasons for corneal transplantation is corneal edema. Edema of the cornea develops from loss of corneal endothelial cells and causes irreversible vision loss in thousands of people yearly. Beyond surgical transplantation of the endothelial cell layer with human donor corneal tissue, no vision-restoring treatments are available. My research investigates the physiology regulating corneal hydration to advance future treatments for these patients. There are two main projects in my lab. The first looks at characterizing changes occurring in endothelial cell monolayer intercellular junctions and passive paracellular transport properties at low and high cell densities. Clinically, patients do not experience deterioration in vision or corneal edema until very low densities. The molecular basis for this observation is unknown. This project investigates changes in the apical junctional complex and monolayer permeability of the endothelium. The second project examines the mechanisms and regulation of active water transport out of the cornea. Using Ussing chamber physiology techniques, my lab is isolating the contributions and regulation of various ionic currents across the corneal endothelium with a focus on the contributions of potassium channels, bicarbonate and carbonic anhydrase inhibitors.
Ophthalmology; Retina; Pediatric Ophthalmology; Pathophysiology; Vision science
Dr. Reynolds has various research interests in pediatric ophthalmology, but his main niche is retinopathy of prematurity. ROP is a disease of the developing immature retinal vasculature, modulated by hyperoxia/hypoxia micro environments in the retina, which can lead to neovascularization, scarring, and potential blindness. Dr. Reynolds is a recognized expert in the field and is the author of many peer reviewed articles and several invited review chapters. His NIH funding has been nearly continuous while at U.B. while participating in several multi-center clinical trials in ROP as center P.I. and project director. Dr. Reynolds was the center P.I. at U.B. for the first large treatment trial for ROP, CRYO-ROP. This trial established the first known effective treatment for this high socioeconomic impact disease. As center P.I. he participated in the group collaborative publications as well as co authoring many individually by-lined papers (Ref. 22, 23, 24, 25, 26, 28, 29, 31, 32, 37, 40, 42). His successful and productive work as a center P.I. on this trial led to the funding for the LIGHT-ROP multi-center trial for which he served as project director and lead P.I. This trial definitively answered a long debated hypothesis in ROP i.e. that ambient light was not a causal factor in ROP (Ref. 38, 41, 45, 47). Dr. Reynolds was again selected as a center P.I. for the next large multi-center ROP trial, ET-ROP, which just reported its primary results demonstrating that earlier laser treatment for this disease was effective. Although all multi-center clinical trials are cooperative agreements at the NIH and thus are funded as UO1s rather than RO1s, Dr. Reynolds was an integral participant in all the ROP trials from the mid-eighties to the present, leading one, and actively co-authoring many of the studies?publications as noted in the bibliography. The future of Dr. Reynolds?ROP research will undoubtedly involve more funded multi-center trials. However, a basic science collaboration into the pathophysiology of ROP in an animal model is planned, investigating the renin-angiotension connection.
Ophthalmology; Retina; Apoptosis and cell death; Gene Expression; Gene therapy; Molecular Basis of Disease; Molecular and Cellular Biology; Neurobiology; Protein Folding; Regulation of metabolism; Signal Transduction; Vision science
The research in my lab has focused on two main areas: 1). molecular mechanisms of inflammation, angiogenesis, vascular and neuronal degeneration in retinal diseases; 2). potential roles of angiogenic inhibitors in obesity, insulin resistance and diabetes. The first line of research centers on gene regulation and signal transduction pathways underlying the neurovascular injury in diabetic retinopathy, retinopathy of prematurity and age-related macular degeneration. In recent years, we are focusing our efforts on the function and mechanism of the UPR signaling in normal and diseased retinal cells. The latter one combines basic and clinical research to study biomarkers and mechanism of type 2 diabetes. 1. ER stress and the UPR signaling in retinal neurovascular injury and diabetic retinopathy. The endoplasmic reticulum (ER) is the primary site for protein synthesis and folding. Failure of this machinery to fold newly synthesized proteins presents unique dangers to the cell and is termed “ER stress.” In response to the stress, cells have evolved an intricate set of signaling pathways named the unfolded protein response (UPR) to restore the ER homeostasis. In addition, the UPR is known to regulates many genes involved in important physiological processes to modulate cell activity and cell fate. The project in my laboratory is aimed to understand the role of ER stress and the UPR in retinal vascular endothelial cell dysfunction and neuronal degeneration in diabetic retinopathy. Our previous work has implicated several key UPR branches such as IRE-XBP1 and ATF4-CHOP in retinal inflammation and vasculopathy in diabetes. Currently, we are employing integrated genetic tools and animal models to study the function of UPR genes in the retina and to dicepher the molecular links between the UPR signaling and inflammatory pathways in retinal cells. Findings from these studies are anticipated to identify novel therapeutic targets and develop new treatments for diabetic retinopathy. 2. Mechanisms and potential therapies for RPE death in age-related macular degeneration. The retinal pigment epithelium (RPE) plays an essential role in maintaining the normal structure and function of photoreceptors. RPE dysfunction and cell death is a hallmark pathological characteristic of age-related macular degeneration (AMD), a disease that accounts for the majority of vision impairment in the elderly. Using transgenic mouse models, we discovered that the transcription factor XBP1 is a critical regulator of oxidative stress and cell survival in RPE cells. Genetic depletion or inhibition of XBP1 sensitizes the RPE to stress resulting in cell death. Our ongoing studies focus on identifying the target genes of XBP1 in RPE cells through which the protein regulates cell survival. We are also investigating if these proteins could offer potential salutary effects to protect RPE cells from oxidative injury and degeneration in disease conditions such as AMD. 3. Roles and mechanisms of angiogenic/anti-angiogenic factors in obesity, insulin resistance and diabetes. Obesity, insulin resistance and Type 2 diabetes are clustered as the most important metabolic disorders, substantially increasing morbidity and impairing quality of life. Excess body fat mass, particularly visceral fat, leads to dysregulation of adipokines (proteins secreted from fat cells), resulting in higher risk of cardiovascular diseases. Our recent findings indicate that angiogenic/anti-angiogenic factors are associated with obesity, diabetes and diabetic complications. For example, pigment epithelium-derived factor (PEDF), a major angiogenic inhibitor, is an active player in adipose tissue formation, insulin resistance and vascular function. In the future, we hope to futher understand the functions and mechanisms of these proteins in lipid metabolism and adiposity. In collaboration with a number of clinical investigators, we are exploring the physiological application of these factors as novel biomarkers and therapeutic targets in the diagnosis and treatment of diabetes, metabolic disorders and peripheral vascular diseases.