Glaucoma: An Open Window to Neurodegeneration and Neuroprotection - Progress in Brain Research, vol. 173 (2008)Edited by:
Carlo Nucci
Luciano Cerulli
Neville N. Osborne
Giacinto Bagetta
Preface
Glaucoma is a family of diseases that includes primary open angle glaucoma (POAG), normal tension glaucoma (NTG), angle-closure glaucoma, secondary glaucoma and glaucoma with onset in infancy. The effect of glaucoma is the death of retinal ganglion cells (RGCs) which causes ultimate loss of vision. The nature of glaucomatous visual field changes and morphologic abnormalities suggests that the pathophysiology reflects injury which occurs at the level of the optic nerve. It remains a matter of debate as to whether this is caused by ischemia at the optic nerve head, blockade of ganglion cell axonal transport, peripapillary atrophy, or changes in the characteristics of the lamina cribosa. Loss of RGCs in glaucoma, especially in POAG and NTG, is gradual with some cells dying ten to twenty years later than others. The challenge for the future is therefore to devise ways of preventing functional RGCs dying once glaucoma is diagnosed. Glaucoma has traditionally been diagnosed by either elevated intraocular pressure (IOP), optic nerve head atrophy of a defined clinical characteristic, or ‘‘cupping’’ and loss of visual field. The current treatment strategy involves medical, surgical, or parasurgical interventions, all aimed at reducing the IOP. This is now widely acknowledged to be insufficient, as many glaucoma patients progress despite treatment and many patients do not have elevated IOP in the first place. Over the past three decades much research has been devoted to discovering novel therapeutic strategies to improve the clinical outcome of the vast majority of patients with glaucoma. In particular, numerous studies have aimed at identifying pharmacological agents that can directly attenuate RGC death as occurs in glaucoma. Much has been learned from experimental studies on animal models of glaucoma and from information related to the treatment of other CNS degenerative diseases. Unfortunately, a large clinical trial stimulated by impressive experimental studies has proved unsuccessful, raising many questions related to neuroprotection strategies for the treatment of glaucoma. It is clear that further progress is necessary before it is possible to translate basic science into clinically effective technologies. Moreover, this goal can only be reached through the development of suitable procedures to monitor disease onset and progression. In this book, leaders in the field of glaucoma contribute articles which shed light on current ideas about the pathophysiology of the disease where putative risk factors require serious consideration. Suitable sensitive procedures for diagnosis and clinical monitoring of the disease need particular thought in order to demonstrate whether a neuroprotection strategy is possible. Topics include experimental models of glaucoma, clinical protocols for the study of neuroprotective therapies, mechanisms underlying glaucomatous damage to neurons of the retina and other ‘‘relay stations’’ in the visual pathway in the brain, and, last but not least, future insights into ways of preventing neuronal injury in glaucoma patients.
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Carlo Nucci, M.D., Ph.D. Associate Professor of Ophthalmology Department of Biopathology and Diagnostic Imaging University of Rome Tor Vergata, Rome, Italy
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Giacinto Bagetta, M.D. Professor of Pharmacology Department of Pharmacobiology University of Calabria Arcavacata di Rende (CS), Italy
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Neville N. Osborne B.Sc., Ph.D., M.A., D.Sc. Professor of Ocular Neurobiology Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford U.K.
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Luciano Cerulli, M.D. Professor of Ophthalmology Department of Biopathology and Diagnostic Imaging University of Rome Tor Vergata, Rome, Italy |
Contents
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Glaucoma: An Open-Window to Neurodegeneration and Neuroprotection |
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Copyright page |
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List of
Contributors
Preface |
Section I. Epidemiology and Clinical Assessment of the Disease
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Epidemiology of primary glaucoma: prevalence, incidence, and blinding effects |
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Predictive models to estimate the risk of glaucoma development and progression |
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Intraocular pressure and central corneal thickness |
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Angle-closure: risk factors, diagnosis and treatment |
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Early diagnosis in glaucoma |
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Monitoring glaucoma progression |
Section II. Anatomical and Functional Monitoring
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Standard automated perimetry and algorithms for monitoring glaucoma progression |
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Short-wavelength automated perimetry and frequency-doubling technology perimetry in glaucoma |
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Scanning laser polarimetry and confocal scanning laser ophthalmoscopy: technical notes on their use in glaucoma |
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The role of OCT in glaucoma management |
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Functional laser Doppler flowmetry of the optic nerve: physiological aspects and clinical applications |
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Advances in neuroimaging of the visual pathways and their use in glaucoma |
Section III. Current Therapy
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Primary open angle glaucoma: an overview on medical therapy |
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The treatment of normal-tension glaucoma |
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The management of exfoliative glaucoma |
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Laser therapies for glaucoma: new frontiers |
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Modulation of wound healing during and after glaucoma surgery |
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Surgical alternative to trabeculectomy |
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Modern aqueous shunt implantation: future challenges |
Section IV. Experimental Approaches to Model Disease
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Model systems for experimental studies: retinal ganglion cells in culture |
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Rat models for glaucoma research |
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Mouse genetic models: an ideal system for understanding glaucomatous neurodegeneration and neuroprotection |
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Clinical trials in neuroprotection |
Section V. Neuroprotection: New Vistas in Pathophysiology
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Pathogenesis of ganglion “cell death” in glaucoma and neuroprotection: focus on ganglion cell axonal mitochondria |
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Astrocytes in glaucomatous optic neuropathy |
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Glaucoma as a neuropathy amenable to neuroprotection and immune manipulation |
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Oxidative stress and glaucoma: injury in the anterior segment of the eye |
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TNF-α
signaling in glaucomatous neurodegeneration |
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Involvement of the Bcl2 gene family in the signaling and control of retinal ganglion cell death |
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Assessment of neuroprotection in the retina with DARC |
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Potential roles of (endo)cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection |
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Glaucoma of the brain: a disease model for the study of transsynaptic neural degeneration |
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Changes of central visual receptive fields in experimental glaucoma |
Section VI. Neuroprotection: Evidence for Future Strategies
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Targeting excitotoxic/free radical signaling pathways for therapeutic intervention in glaucoma
Stem cells for
neuroprotection in glaucoma |
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The relationship between neurotrophic factors and CaMKII in the death and survival of retinal ganglion cells |
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Evidence of the neuroprotective role of citicoline in glaucoma patients |
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Neuroprotection: VEGF, IL-6, and clusterin: the dark side of the moon |
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Rational basis for the development of coenzyme Q10 as a neurotherapeutic agent for retinal protection |
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17β-Estradiol prevents retinal ganglion cell loss induced by acute rise of intraocular pressure in rat |
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Subject Index |
