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Anne Messer, Ph.D.
Wadsworth Center
Albany, NY
Title:
Anti-Drusen Nanobodies for AMD
Non-Technical Title:
Small antibody fragments as potential AMD therapeutics/ drug discovery tools
Duration:
April 1, 2010 - March 31, 2012
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Summary: Drusen develop as yellow deposits under the retina and are considered to be hallmarks of age-related macular degeneration; this proposal utilizes cutting-edge recombinant antibody technologies to develop novel anti-drusen “nanobody” molecules that have the potential to serve as direct therapeutics and/or drug discovery tools for AMD. Nanobodies can be selected, engineered, and manipulated as genes, then delivered as either genes or proteins to modulate drusen. Since similar reagents are already in human clinical trials for other abnormal protein diseases, translation to clinical ophthalmology is highly feasible.
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Program: Macular Degeneration
Award Type: Standard
$100,000
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Scott Plafker, Ph.D.
University of Oklahoma Health Sciences Center
Oklahoma City, OK
Title:
Countering Oxidative Stress In The Retina With The Ubiquitin System
Non-Technical Title:
Blocking Stress In Retinal Cells
Duration:
April 1, 2009 - March 31, 2011
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Summary: The aim of this application is to test the hypothesis that the ubiquitin system can be manipulated to augment the inherent anti-oxidant system present in retinal pigment epithelial (RPE) cells and photoreceptors. The ubiquitin system is one of the methods that cells use to destroy old or unnecessary proteins, and can be used to help regulate the activities of cellular protein. This hypothesis will be tested in mice using a virus to over-express a ubiquitin conjugating enzyme (UbcM2) coupled to a well-established, light-stress model of retinal degeneration.
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Program: Macular Degeneration
Award Type: Standard
$100,000
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Roxana Radu, M.D.
UCLA - Jules Stein Eye Institute
Los Angeles, CA
Title:
Analysis of A2E-degradation and Complement Activation in Two New Animals Models for Age-related Macular Degeneration
Non-Technical Title:
The Role of Lipofuscin Pigments and Chronic Inflammation as a Cause of Macular Degeneration
Duration:
April 1, 2008 - June 28, 2010
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Summary: This project will test the hypothesis that abnormal metabolism of vitamin A and its derivatives could lead to overt activation of the immune complement system. It will test this hypothesis using a well established animal model of macular defects. They will investigate the biochemical and molecular mechanisms used by the retina to deal with abnormal build-up of vitamin A-based toxic compounds.
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Program: Macular Degeneration
Award Type: Standard
$100,000
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Euijung Ryu, Ph.D.
Mayo Clinic
Rochester, MN
Title:
Pathway discovery in macular degeneration using genome-wide proteome, transcriptome and epigenetic analyses
Non-Technical Title:
Pathway discovery in macular degeneration using bioinformatic approaches
Duration:
April 1, 2010 - March 31, 2012
Co-Investigator(s):
Kent Bailey,
Mayo Clinic
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Summary: We are identifying the molecular biological pathways altered by the genetic variants across the ARMS2 genomic region, or locus, in human retina. This study uses sophisticated "omics" approaches to accomplish these goals.
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Program: Macular Degeneration
Award Type: Standard
$100,000
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Hendrik Scholl, M.D.
Wilmer Eye Institute
Baltimore, MD
Title:
Structure-Function Correlation in Macular Degeneration
Non-Technical Title:
Structure-Function Correlation in Macular Degeneration
Duration:
April 1, 2010 - March 31, 2012
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Summary: This study may be the first methodology for an exact point-by-point structure-function correlation of pathology within the central retina. This diagnostic technology is extremely promising to establish new surrogate endpoints for clinical trials and for monitoring treatment effects on visual function with highest accuracy.
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Program: Macular Degeneration
Award Type: Standard
$100,000
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Fu Shang, Ph.D.
Tufts University
Boston, MA
Title:
Impairment of the UPP and choroidal neovascularization
Non-Technical Title:
Dysfunction of protein degradation machinery in RPE may cause AMD
Duration:
April 1, 2010 - March 31, 2012
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Summary: The ubiquitin-proteasome pathway (UPP) plays critical roles in various cellular functions, including signal transduction, transcription, cell cycle and protein quality control. This project is to test a novel hypothesis that age- and stress-related impairment of the UPP in RPE is a key contributor to the pathogenesis of age-related macular degeneration (AMD) using transgenic mice to specifically impair the UPP in the retinal pigmented epithelia (RPE). Results obtained from this study will not only help understand the pathogenesis of AMD, but also potentially provide a novel animal model of AMD that could be used to screen potential therapeutic compounds for treatment or prevention of this devastating disease.
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Program: Macular Degeneration
Award Type: Standard
$100,000
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Justine Smith, M.D., Ph.D.
Oregon Health and Science University
Portland, OR
Title:
Novel Molecular Regulators of Choroidal Neovascularization in Age-Related Macular Degeneration
Non-Technical Title:
Control of New Blood Vessel Growth in Macular Degeneration
Duration:
April 1, 2008 - June 29, 2010
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Summary: This research group has developed a technique for isolation of endothelial cells of the choroid from human eyes that are supplied by the Lions Eye Bank of Oregon. In this project, they will study three molecules that are produced at high levels in tissues related to AMD. They will test the ability of these molecules to control the formation of new blood vessels.
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Program: Macular Degeneration
Award Type: Standard
$100,000
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Dwight Stambolian, M.D., Ph.D.
University of Pennsylvania
Philadelphia, PA
Title:
Potential Therapy of Age-Related Macular Degeneration with Small Molecules
Non-Technical Title:
Small molecule therapy for Macular Degeneration
Duration:
April 1, 2008 - June 30, 2010
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Summary: This project is looking for a small molecule which can penetrate the eye and diminish the eye inflammation that occurs in AMD. If successful, this small molecule can be administered at the earlier stages of AMD to halt progression to the later stages and eventual blindness. In order to identify such a molecule, we will screen a small molecule library and confirm its efficacy in a test tube before moving onto animal models.
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Program: Macular Degeneration
Award Type: Standard
$100,000
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Jeffrey Stern, M.D., Ph.D.
Regenerative Research Foundation
Rensselaer, NY
Title:
alphaB-crystallin and the Amyloid-beta mediated RPE stress response in Age related Macular Degeneration
Non-Technical Title:
The role of Alzheimer Disease protein and the stress response in AMD
Duration:
April 1, 2008 - May 31, 2010
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Summary: A protein related to Alzheimer's disease is known to be present in cases of AMD. This proposal will examine a toxic product of this protein and ask whether it is involved in the development of AMD.
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Program: Macular Degeneration
Award Type: Standard
$100,000
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Jie Jin Wang, Ph.D.
Centre for Eye Research Australia, The University of Melbourne
Melbourne, Australia
Title:
Epigenetic dissection of age-related macular degeneration
Non-Technical Title:
How do genes and environmental influences interact to cause macular degeneration?
Duration:
April 1, 2010 - March 31, 2012
Co-Investigator(s):
Alex Hewitt, M.D., Ph.D.
Centre for Eye Research Australia, The University of Melbourne
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Summary: Given the development of anti-angiogenic agents, vision loss resulting from neovascular, ‘wet’, age-related macular degeneration (AMD), should be largely preventable if diagnosed early. Methylation patterns of AMD-related genes should identify subjects who are at high risk of neovascular AMD. Ultimately, this project could lead to the development of diagnostic tests and identify novel treatment pathways that modify gene expressions.
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Program: Macular Degeneration
Award Type: Standard
$96,780
