The Optic Nerve Research Center of Maryland has been created to test novel neuroprotective drugs, gene therapies, and progenitor cell (ie, stem cell) replacement in animal models, in preparation for testing them in humans.
The fundamental role of the ophthalmologist is to preserve and to restore vision. Although ophthalmologists have been successful in a number of areas, including treatment of cataracts and diseases of the cornea and retina, our treatment of optic nerve disease is much less successful. Processes that damage the optic nerve, including elevated intraocular pressure (ie, glaucoma), trauma, stroke, pressure from brain tumors, and hereditary conditions, often cause visual loss for which there is no treatment.
It has long been believed that patients who suffer damage to the optic nerve will never regain useful vision because the nerve cannot regenerate or repair itself. This belief is based on three assumptions: (1) a mammalian retinal nerve cell, or neuron, cannot be prevented from dying once its cell body or its axon has been injured; (2) an injured mammalian neuron whose axon has degenerated cannot be induced to extend a new axon; and (3) even if an injured retinal neuron could be induced to regenerate, the regenerating axon cannot be directed toward its correct target in the central nervous system.
In fact, evidence from experimental studies in mammals, including nonhuman primates, is accumulating that under certain conditions, retinal neurons can be prevented from dying despite injury to the cell bodies or their axons, injured retinal neurons whose axons have degenerated can be induced to extend new axons, and regenerating axons can reach their correct targets in the central nervous system.
In fact, evidence from experimental studies in mammals, including nonhuman primates, is accumulating that under certain conditions, retinal neurons can be prevented from dying despite injury to the cell bodies or their axons, injured retinal neurons whose axons have degenerated can be induced to extend new axons, and regenerating axons can reach their correct targets in the central nervous system.
Several steps are necessary for successful treatment of optic nerve injury. First, the death of retinal ganglion cells that have been (or have the potential to be) damaged must be prevented. Second, living retinal ganglion cells whose axons have degenerated must be induced to extend new axons toward their targets in in the central nervous system. Finally, a process of synaptic connection and refinement must occur so that appropriate retinal ganglion cells are connected to the appropriate target in a retinotopic distribution. Prevention of the death of retinal ganglion cells usually is referred to as neuroprotection, whereas restoration of optic nerve function after injury is called neurorepair.
A variety of strategies can be used to both protect and repair damaged optic nerves; however, work currently advances slowly, in part because of the need to thoroughly test such strategies in at least two species of animals before trying them in humans and in part because of the considerable cost involved in animal research. Nevertheless, with funding from institutions such as the National Eye Institute of the National Institutes of Health and the Hirschhorn Foundation as well as from individual donors, we have been able to develop reproducible models of optic nerve damage in rats, mice, and, most importantly, in monkeys. These models allow us to test various substances that have the potential to reduce the amount of optic nerve damage caused by various insults or to restore vision that is lost from optic nerve damage. With this knowledge, we can then begin testing on humans.
A variety of strategies can be used to both protect and repair damaged optic nerves; however, work currently advances slowly, in part because of the need to thoroughly test such strategies in at least two species of animals before trying them in humans and in part because of the considerable cost involved in animal research. Nevertheless, with funding from institutions such as the National Eye Institute of the National Institutes of Health and the Hirschhorn Foundation as well as from individual donors, we have been able to develop reproducible models of optic nerve damage in rats, mice, and, most importantly, in monkeys. These models allow us to test various substances that have the potential to reduce the amount of optic nerve damage caused by various insults or to restore vision that is lost from optic nerve damage. With this knowledge, we can then begin testing on humans.
Laboratory research in this program is under the overall supervision of Dr. Steven L. Bernstein, MD PhD, Professor of Ophthalmology and Visual Sciences at the University of Maryland Medical Center, Neil R. Miller, MD FACS, Professor of Ophthalmology, Neurology & Neurosurgery and the Frank B. Walsh Professor of Ophthalmology at Johns Hopkins University School of Medicine, and Mary A. Johnson, PhD, Associate Professor of Ophthalmology and Visual Sciences and Head of the Electrophysiology Section at the University of Maryland Medical Center, all of whom have extensive experience with both clinical and research issues relating to optic nerve disease.
The laboratory uses a number of interdisciplinary approaches to study optic nerve disease. We are using the following techniques in our current studies:
· Immunohistochemistry using confocal microscopy
· High-resolution ICG angiography using autologous injection of ICG-tagged erythrocytes.
· Magnetic resonance imaging
· Optical coherence tomography
· Advanced electrophysiologic recording
· Fluorescein angiography and fundus photography
· Molecular analysis of the genetic response to optic nerve stroke
· Two-photon microscopy
· Laser microdissection
Electron microscopy
· Stem cell culture
We will continue to integrate new technologies to develop treatments to prevent or lessen vision loss from optic nerve disorders.
· Immunohistochemistry using confocal microscopy
· High-resolution ICG angiography using autologous injection of ICG-tagged erythrocytes.
· Magnetic resonance imaging
· Optical coherence tomography
· Advanced electrophysiologic recording
· Fluorescein angiography and fundus photography
· Molecular analysis of the genetic response to optic nerve stroke
· Two-photon microscopy
· Laser microdissection
Electron microscopy
· Stem cell culture
We will continue to integrate new technologies to develop treatments to prevent or lessen vision loss from optic nerve disorders.