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Vision allows us to perceive the universe around us. The initial interaction of visual stimuli with the nervous system occurs in the retina. Located in the back of the eye, the retina is a highly organized, laminated structure that contains several types of neurons (e.g. photoreceptors, bipolar, amacrine, horizontal and retinal ganglion cells) and glial cells. The retina and optic nerve are extensions of the central nervous system (CNS). Due to its accessibility, the retina is an ideal system to study the biology of CNS neurons and glia in health and disease. In particular, we have focused on the biology of retinal ganglion cells. These neurons have their cell bodies in the inner retina in the eye, and axons along the optic nerve that reach visual targets in the brain. Therefore, retinal ganglion cells are the sole neurons that convey visual information from the retina to the brain.
Injury to the CNS of adult mammals leads to neuronal death, axon damage and persistent functional deficits. Axonal degeneration is a hallmark of traumatic or ischemic injury and neurodegenerative diseases. CNS neurons have a limited capacity to survive or regrow their axons after injury. Several factors have been associated with poor regeneration including neurotrophic factor deprivation, presence of growth inhibitory molecules, and formation of the glial scar. Our research program focuses on the identification of molecular cues that regulate neuronal survival and regeneration in the injured visual system. Specifically, we aim to characterize the response of retinal ganglion cells to injury and to identify extrinsic and intrinsic factors that stimulate the ability of these neurons to survive and regrow an axon. We are currently investigating the role of neurotrophic factors and downstream signaling targets, molecular mechanisms involved in apoptosis, and signals that regulate the morphology and function of retinal ganglion cells after axonal injury. Our goal is to use this knowledge to develop strategies to enhance retinal ganglion cell survival and axon regeneration in models of optic nerve injury in vivo.
Glial cells play pivotal roles in the function of the nervous system: they provide direct metabolic support, regulate the neuronal microenvironment, and actively contribute to neuronal activity. The mammalian retina contains 3 types of glial cells: Müller cells (radial glia), astrocytes and microglia. Müller cells are the most abundant glial cell type in the retina. They span the entire thickness of the retina and have secondary processes that closely wrap around neuronal cell bodies and dendrites. Müller cell gliosis has been proposed to be neuroprotective in the early stages after retinal injury, perhaps reflecting a cellular response to protect the tissue from further damage. However, these initial benefits can become detrimental when injury is pronounced or during chronic damage as in most retinal degenerations. Indeed, recent data from our laboratory indicate that Müller glia can exacerbate neuronal death in pathological conditions. Current research in our laboratory aims to characterize the molecular mechanisms by which Müller cells control the survival of retinal ganglion cells after injury.
Glaucoma is the second leading cause of blindness worldwide, after cataract. It has been estimated that >50 million persons are affected by glaucoma, with >7 million people presenting bilateral blindness caused by this disease. There are several types of glaucoma, including primary open angle, angle-closure and congenital glaucoma. A common characteristic of all types of glaucoma is the death of retinal ganglion cells. When there is substantial loss of these neurons, the patient experiences gradual and progressively worsening vision. Although the direct cause of glaucoma is unknown, several major risk factors have been identified including age and high intraocular pressure. At present, there is no cure for glaucoma and current treatments are often insufficient to stop disease progression. We strive to understand the mechanisms underlying retinal ganglion cell death in glaucoma and to develop novel neuroprotective therapies to preserve and restore vision
To apply for a research or student position in the Di Polo lab, please send your CV to: firstname.lastname@example.org
© Département de pathologie et biologie cellulaire, 2011