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Top-Ten Glaucoma and other neurodegenerations: a scientific meeting
May 2001, Sarasota, FL, USA
Martin Wax
In May 2001, Research to Prevent Blindness sponsored a unique scientific four-day conference in Sarasota, Florida, which was attended by approximately 20 of the world's leading investigators focused on the study of mechanisms thought to be relevant to neuronal death in chronic disease. The meeting was chaired by Martin B. Wax, MD, from Washington University. Investigators presented studies on basic cellular mechanisms, pathophysiology, and candidate approaches used to study neuronal death in a variety of diseases including Alzheimer's, Parkinson's, multiple sclerosis, immune-mediated neuropathies. and Huntington's disease. The main purpose of the workshop was to foster interchange and discussion as glaucoma was considered in the context of these well-studied neuronal degenerations. The highlight of the meeting was the common realization that general mechanisms of neurodegeneration have broad applicability to all the diseases studied. For example, a synaptic disconnection, or dendritic synaptic field withdrawal (known as ' dropback') occurs in affected target organs innervated in each neuronal degeneration. Furthermore, this dropback occurs relatively early in all neurodegenerations and may be a useful locus of intervention as we seek to discover ways to prevent neuronal death in each relevant disease. The meeting proceedings will be published in detail this fall in a special edition of Current Eye Research.
The most interesting questions and comments made by other investigators that were pertinent to the field of glaucoma and glaucoma research include the following 'Top 10':
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We should take advantage of animal models of glaucoma to better study mechanisms of neuronal cell death in response to selected stressors, such as elevated intraocular pressure, ischemia, cytokines, neurotrophin withdrawal, etc. Glaucoma may be uniquely positioned in this regard since our animal models appear very useful and easy to establish. In particular, we should focus our efforts on retinal circuitry to study the signalling between astrocytes and RGCs and between dying and healthy RGCs.
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Better histopathology studies are needed. Older studies from the past 20 or 30 years do not take advantage of the wealth of new scientific information that can now be ascertained by modern histochemical markers of cell death mechanisms.
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Susceptibility factors for selective vulnerability should be sought. We should carefully examine glaucomatous eyes for markers of oxidative stress (nitrotyrosine markers, protein carbonyls), caspase markers, hypoxia markers, etc., in order to determine what makes glaucoma eyes susceptible to cell death. What HLA changes occur in antigen presenting cells, or in other modulatory proteins such as Apo E4/E2, in glaucomatous eyes?
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Studies should seek to learn whether there is commonality at the end-stage of disease, regardless of initiating events.
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Is necrosis as important as apoptosis in glaucoma? Are we dismissing necrosis too readily as a putative mechanism of cell death?
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What are upstream stimuli for cell death in glaucoma? At what point can we remove initiating events and still retain useful function?
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We need a surrogate marker for disease in clinical trials and outcome studies.
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We should collect samples for genetic and blood analysis, and look for genes that make the glaucomatous eye susceptible to damage, and seek to identify serum proteins that are either causative or contributory factors in disease progression.
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We need a cooperative approach among agencies to study preclinical/clinical correlations in glaucoma that has an adequate infrastructure to ensure success.
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We must learn the lessons of clinical trials from other fields and segregate our patients correctly prior to analysis.
