Progress 01/11/00 to 04/30/04
Outputs
1. What major problem or issue is being resolved and how are you resolving it (summarize project aims and objectives)? How serious is the problem? What does it matter? Age-related cataract is a major public health problem. Worldwide it is the major cause of preventable blindness. In the United States (US) approximately 20 to 50 % of persons 65-74 and 75 years of age, respectively, have age-related cataract which results in visual impairment. Cataract appears in the posterior subcapsular, cortical, and nuclear portions of the eye lens. Over $6 billion is spent each year on cataract-related expenses. Delay of the onset or progress of cataract are important public health concerns, since over 1.2 million eye-lens extractions are performed annually in the US. Costs associated with cataract extractions in the US account for the largest line, 12%, of the total Medicare budget. It is estimated that delaying cataract by only 10 years would diminish by 50% the number of
cataract extractions required. Age-related maculopathy is a blinding condition involving degeneration of the retina's macula that is responsible for central vision. There is no surgical cure or treatment for this blinding condition, which afflicts approximately 6 percent of the elderly. Nor is there a clear path toward the cure. The compromises in quality of life of our elderly and burden to our health care budgets provide major incentives to explore the etiology of cataract and to discover means to delay cataract onset and/or progression. Specifically, this CRIS is also determining the extent to which diets rich in certain foods or nutrients can offer protection against these vision debilities. Research within this CRIS falls under the National Program 107 Human Nutrition Action Plan components 1: Nutrient requirements and 2: Diet, genetics, lifestyle, and the prevention of obesity and disease. 2. List the milestones (indicators of progress) from your Project Plan. Replacement
Project was certified on March 8, 2004 by OSQR. Please see the report for 1950-51000-060-00D Nutrition, Aging and Visual Function. 3. Milestones: Replacement Project was certified on March 8, 2004 by OSQR. Please see the report for 1950-51000-060-00D Nutrition, Aging and Visual Function. 4. What were the most significant accomplishments this past year? A. Single Most Significant Accomplishment during FY2004: The accumulation of damaged proteins is partly responsible for cataract formation and age-related macular degeneration. HNRCA scientists are investigating roles for the major protein editing system, called the ubiquitin system, in these diseases. To test hypotheses that the ubiquitin system is involved in the removal of damaged proteins, researchers made a mutant ubiquitin, a unique molecule that forms complexes which are not degraded, even though part of these complexes contain cellular molecules that should be removed in order to avoid disease. We demonstrated that the
ubiquitin proteolytic pathway selectively recognizes oxidized proteins. We also showed that a compromise in the degradation of the ubiquitin conjugates leads to protein insolubilization. This also occurs in cataract. We corroborated data that emphasizes the need to define and retain protein quality control to prolong visual function. This is probably achievable through dietary means. B. Other Significant Accomplishments: 1. With collaborators in the HNRCA Nutritional Epidemiology Program and at Harvard University, the laboratory is conducting a study that seeks to determine whether and how nutrient intake is related to risk for onset and progression of cataract and age-related maculopathy. Scientists gathered lens and retina images and obtained access to The Nurses' Health Study nutrient intake and personal lifestyle databases. We found that moderate alcoholic beverage is related to risk for cortical and nuclear early lens opacities. Specifically, moderate wine intake provided
diminished risk for age-related lens cortical opacities. Consuming higher levels of fruits and whole grains provided diminished risk for cataract. 2. In another collaboration with the Nutritional Epidemiology Program, scientists showed that the chance of developing for posterior subcapsular cataract are lower in persons with higher abdominal adiposity and observed that eating according to the recommendations of the Dietary Guidelines for Americans is associated with diminished risk for nuclear cataract. These results emphasize the value of the Dietary Guidelines as a nutritional guide. 3. Demonstration that there are important interactions between glutathione, vitamins C and E. These are particularly important and obvious when cells are oxidatively stressed. These results emphasize the need to understand biological synergies between nutrients. 4. We pursued the relationships between oxidative stress, protein quality control and proteolytic function in efforts to determine the
mechanisms that may exist that allow cells to function longer when nutrition is optimized. These results emphasize the role of nutrition in healthy cell function. C. Significant Activities that Support Special Target Populations: None. 5. Describe the major accomplishments over the life of the project, including their predicted or actual impact. Studies conducted within this CRIS indicate that the protein quality control mechanisms are compromised by the oxidative stresses, and that these compromises may be related to cataract and age-related macular degeneration (AMD). Optimal nutrition can extend control of the quality control machinery. Furthermore, not only can the prevalence of cataract and age-related maculopathy be diminished by appropriate nutrition early in life, but also, the amount of public health resources committed to their treatment can be contained if people follow optimal diets for prolonging visual function. Data from our studies should be considered when the
Dietary Reference Intakes (DRIs) are reevaluated. Action Plan component 2: Diet, genetics, lifestyle, and the prevention of obesity and disease. 6. What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end- user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products? The laboratory made available to the nutrient/food industry estimates of what foods, groups of foods and supplements should contain as a means to optimize protection of the eye during aging. These are available now and should be considered as DRIs are evaluated. Investigators have adapted modern techniques in proteomics and RNAi technologies that are now available for use by other HNRCA. We also have available mutant ubiquitins, which can diminish progress of secondary cataract and cancer progress. 7. List your most important publications in the popular press
and presentations to organizations and articles written about your work. Presentation(s) Eat well, drink a little and stay thin if you want to see well-results from the Nutrition and Vision Project. Feb 2004. Cooperative Cataract Research Group meeting, Kona, Hawaii. Specificity of Ubiquitination for Oxidatively Modified Proteins. Feb 2004. Cooperative Cataract Research Group meeting, Kona, Hawaii. Nutritional Correlates of Risk for Age-related Eye Diseases: Ready for Changes in Policy?" April 2004. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA. Long-term Dietary Carbohydrate Intake and Glycemic Index and Early Cortical and Nuclear Lens Opacities. April 2004. Association for Research in Vision and Ophthalmology. Fort Lauderdale, FL. Lens cells have a ubiquitin-dependent chaperone activity. April 2004. Association for Research in Vision and Ophthalmology. Fort Lauderdale, FL. Proteasome Activity Is Required for Lens Cell Differentiation. April 2004.
Association for Research in Vision and Ophthalmology. Fort Lauderdale, FL. Specificity Of Ubiquitination For Oxidatively Modified Proteins. April 2004. Association for Research in Vision and Ophthalmology, Fort Lauderdale, FL. Expression of K6w Ubiquitin Variant in Epithelial Cells Causes Lens Abnormalities. May 2004. Cold Spring Harbor Symposia, Cold Spring Harbor, NY. Ask the Experts. ARS 50th Anniversary celebration. May 2004. USDA/HNRCA, Tufts University, Boston, MA. Selectivity of the Ubiquitin Pathway for Oxidatively Modified Proteins: Relevance to Protein Precipitation Diseases. June 2004. FASEB Conference: Ubiquitin and Cellular Regulation, Saxtons River, VT. Specificity of ubiquitination for oxidatively modified proteins. June 2004. Role of Gas6/Axl signaling in lens epithelial cell growth and protection from apoptosis. American Society for Biochemistry and Molecular Biology Conference, Boston, MA.
Impacts
(N/A)
Publications
- Shang, F., Lu, M., Dudek, E., Reddan, J., Taylor, A. 2003. Vitamin c and vitamin e restore the resistance of gsh-depleted cells to h2o2. Free Radical Biology And Medicine. 34(5):521-530.
- Lu, Q., Shang, F., Guo, W., Hobbs, M., Valverde, P., Reddy, V., Taylor, A. 2004. Regulation of the ubiquitin proteasome pathway in human lens epithelial cells during the cell cycle. Experimental Eye Research. 78(2) :197-205.
- Valverde, P., Obin, M.S., Taylor, A. 2004. Role of gas6/axl signaling in lens epithelial cell proliferation and survival. Experimental Eye Research. 78:27-37.
- Shang, F., Taylor, A. 2004. Function of the ubiquitin proteolytic pathway in the eye. Experimental Eye Research. 78:1-14.
- Pereira, P., Shang, F., Girao, H., Taylor, A., Hobbs, M. 2003. Lens fibers have a fully functional ubiquitin-proteasome pathway. Experimental Eye Research. 76:623-631.
- Shang, F., Guo, W., Liu, Q., Taylor, A. 2004. Lens cells have a ubiquitin- dependent chaperone activity. Association for Research in Vision and Ophthalmology. Available: http://www.abstractsonline. com/viewer/viewAbstract.asp?AKey=%7B01DBD563-E053-4A16-A83F- 48E737512973%7D&MKey=%7BCE5329F2-F251-4D11-9051- 8C6E9E9E1528%7D&SKey=%7B7D110C4C-A675-4577-9298- A7255CAE3B22%7D&CKey=%7B5C45E3D1-A408-41C2-ACB8-24B5636B4605%7D
- Taylor, A., Dudek, E., Liu, Q., Shang, F. 2004. Specificity of ubiquitination for oxidatively modified proteins. Association for Research in Vision and Ophthalmology. Available: http://www.abstractsonline. com/viewer/viewAbstract.asp?AKey=%7B01DBD563-E053-4A16-A83F- 48E737512973%7D&MKey=%7BCE5329F2-F251-4D11-9051- 8C6E9E9E1528%7D&SKey=%7B74694EA9-652C-4551-AD9D- 51C9B90C1B08%7D&CKey=%7B923AAB07-9A24-4019-9D1A-78B0809B82F8%7D
- Guo, W., Shang, F., Liu, Q., Urim, L., Taylor, A. 2004. Proteasome activity is required for lens cell differentiation. Association for Research in Vision and Ophthalmology. Available:http://www.abstractsonline. com/viewer/viewAbstract.asp?AKey=%7B01DBD563-E053-4A16-A83F- 48E737512973%7D&MKey=%7BCE5329F2-F251-4D11-9051- 8C6E9E9E1528%7D&SKey=%7B91E1B17D-A81F-4C0C-AAA8- 269C637BDF13%7D&CKey=%7B14B0E489-5E03-46B5-A025-489D00D930B8%7D
|
Progress 10/01/02 to 09/30/03
Outputs
1. What major problem or issue is being resolved and how are you resolving it? Age-related cataract is a major public health problem. Worldwide it is the major cause of preventable blindness. In the United States approximately 20 and 50 % of persons 65-74 and 75 years of age, respectively, have age-related cataract which results in visual impairment. Cataract appears in the posterior subcapsular, cortical, and nuclear portions of the eye lens. Age-related maculopathy is a blinding condition involving degeneration of the retina's macula, that is responsible for central vision. There is no surgical cure or treatment for this blinding condition which afflicts approximately 6 percent of the elderly. The compromises in quality of life of our elderly and burden to our health care budgets provide major incentives to explore the etiology of cataract and to discover means to delay cataract onset and/or progression. This CRIS is also determining the extent to which diets
rich in certain foods or nutrients can offer protection against these vision debilities. 2. How serious is the problem? Why does it matter? Cataract afflicts more than half of the aged population. Over $6 billion is spent each year on cataract-related expenses. Delay of the onset or progress of cataract are important public health concerns, since over 1.2 million eye-lens extractions are performed annually in the United States. Costs associated with cataract extractions in the Unites States account for the largest line, 12%, of the total Medicare budget. It is estimated that delaying cataract by only 10 years would diminish by 50% the number of cataract extractions required. Age-related maculopathy afflicts approximately 6 percent of the elderly. To date there is no surgical cure or treatment for this blinding condition, nor is there a clear path toward the cure. 3. How does it relate to the National Program(s) and National Program Component(s) to which it has been assigned?
This CRIS addresses goals listed under the National Program 107 - Human Nutrition. Specifically, components "nutrient requirements" and the "relationship between diet, genetics and lifestyle and the risk for chronic disease," are addressed. This program focuses on the extent to which increased levels of intake of various nutrients are associated with reduced risk for age-related retinal degeneration and age-related cataract. 4. What were the most significant accomplishments this past year? A. Single Most Significant Accomplishment: The HNRCA is conducting a study that seeks to determine whether and how nutrient intake is related to risk for onset and progression of cataract and age-related maculopathy. With collaborators at Harvard University, scientists gathered lens and retina images and obtained access to Nurses' Health Study nutrient intake and personal lifestyle databases. Investigators observed that progress of nuclear cataract is slowed in persons who took vitamin E
supplements for more than 10 years. Since it is predicted that a delay of only 10 years would decrease by half the need for cataract extractions, this information would provide for enhanced quality of life for the elderly by prolonging their sight without surgery. B. Other Significant Accomplishments: 1. Analysis of information from the Nutrition and Vision Project showed that chances for nuclear cataract are lower in persons with higher abdominal adiposity and that eating according to the USDA Food Guide Pyramid is associated with diminished risk for nuclear cataract. Consuming higher levels of fruits and whole grains provided diminished risk for cataract. While total alcohol intake was associated with higher risk for cataract, moderate wine intake provided diminished risk for age- related lens cortical opacities. These results emphasize the value of the USDA Food Guide Pyramid as a nutritional guide. C. Significant Activities that Support Special Target Populations: None. D.
Progress Report: It is clear that the accumulation of damaged proteins is partly responsible for cataract formation and age-related macular degeneration. Scientists at the HNRCA are investigating roles for the major protein editing system, called the ubiquitin system, in these diseases. To test hypotheses that the ubiquitin system is involved in removal of damaged proteins, researchers made a mutant ubiquitin, a unique molecule that forms complexes which are not degraded, even though part of these complexes contain cellular molecules that should be removed in order to avoid disease. We demonstrated that oxidized proteins are selectively recognized by the ubiquitin proteolytic pathway. 5. Describe the major accomplishments over the life of the project, including their predicted or actual impact. Studies conducted within this CRIS indicate that not only can the prevalence of cataract and age-related maculopathy be diminished by appropriate nutrition early in life, but also, the amount
of public health resources committed to their treatment can be contained if people follow optimal diets for prolonging visual function. 6. What do you expect to accomplish, year by year, over the next 3 years? Project is currently involved in the OSQR Review Process for NP 107 (Human Nutrition). 7. What science and/or technologies have been transferred and to whom? When is the science and/or technology likely to become available to the end- user (industry, farmer, other scientists)? What are the constraints, if known, to the adoption and durability of the technology products? The laboratory made available to the nutrient/food industry estimates of what supplements should contain as a means to optimize protection of the eye during aging. Investigators have adapted modern techniques in proteomics that are now available for use by other HNRCA scientists. We will probably have availably mutant ubiquitins which can alter cancer progress. 8. List your most important publications in the
popular press and presentations to organizations and articles written about your work. (NOTE: This does not replace your peer-reviewed publications listed below). PRESENTATION(S) Nestle Seville Conference on Aging and Nutrition. June 2001. Ubiquitin and Ataxia Telangiectasia. Tel Aviv University. June 2001. Nutrition and Risk for Cortical and Posterior Subcapsular Cataract in the Nutrition and Vision Project. Academy of Ophthalmology: New Orleans, LA October 2001. Nutrition and Risk for Cortical and Posterior Subcapsular Cataract. Teleconference. October 2001. HNRC Research in the Lab for Nutrition and Vision Research Tufts. October 2001. HNRC Nutrition and Genomics: harnessing the power of colorie restriction. November 2001. Oxidative Stress, Protein Degradation and Disease. Department of Pharmacology, Tufts University. November 2001. WB56 Television news interview. December 19, 2001. Davis, J. Vitamin C protects against cataracts: but smoking decreases body's use of antioxidants.
http://health.msn.com. February 22, 2002. Roles for Antioxidant Nutrients in Delay of Cataract over 5 years in the Nutrition and Vision Project. Columbia University. Department of Pharmacology, Tufts University. March 2002. Ha'aretz (Israeli newspaper) and Ha'aretz Online. March 24, 2002. Nutrients, Beer, Protein-Turnover and Your Vision. April 2002. Oxidation and ubiquitin function in the eye. Case Western University. March 2003. Nutritional correlates of risk for age-related eye diseases-ready for changes in policy? Friedman School of Nutrition, Tufts University. March 2003. Relations between Nutrient Intake and Risk for Cataract. Nutrient Manufacturers Association. April 2003. Alcohol intake as a risk factor for cataract. Association for Research in Vision and Ophthalmology. April 2003. The lens as a system to study age-related changes to protein editing capabilities- and what you can do about them. May 2003. Oxidative Stress and Ubiquitination Meet Nutrition in the Eye.
Technion, Israel Institute for Technology. May 2003. Can we use nutrition to delay cataract or AMD? Dept of Ophthalmology, Tufts University. June 2003. Protein Oxidation, The Ubiquitin Pathway, and Nutrition meet in the Lens. Tufts Center for Vision Research. June 2003. ARTICLES Shang, F., Nowell, T., Gong, X., Smith, D.E., Dallal, G.E., Taylor, A. Sex-linked differences in Cataract Progression in Emory Mice. Experimental Eye Research. 2002. v. 75. p. 109-111. Obin, Y., Lee, B.Y., Meinke, G., Bohm, A., Lee, R.H., Gaudet, R., Hopp, J.A., Arshavsky, V.Y., Willardson, B.M., Taylor, A. Ubiquitilyation of the Transducin ss? Subunit Complex: Regulation by Phosducin. Journal of Biological Chemistry. 2002. v. 277. p. 44566-44575. Hall, M.O., Obin, M.S., Prieto, A.L., Burgess, B.L., Abrams, T.A. Gas6 binding to photoreceptor outer segments requires ?-carboxyglutamic acid (Gla) and Ca2+ and is required for OS phagocytosiis by RPE cells in vitro. Experimental Eye Research. 2002. v. 75. p.
391-400. Hao, W., Wenzel, A., Obin, M.S., Chen, C-K., Brill, E., Krasnoperova, N. V., Eversole-Cire, P., Kleyner, Y., Taylor, A., Simon, M.I., Grimm, C., Reme, C.E., Lem, J. Evidence for Two Apoptotic Pathways in light-Induced Retinal Degenerations. Nature Genetics. 2002. v. 32. p. 254-260. Shang, F., Lu, M., Dudek, E., Reddan, J., Taylor, A. Vitamin C and Vitamin E Restore the Resistance of Glutathione-depleted Lens Epithelial Cells to Peroxide. Free Radic Research. 2003. v. 34. p. 521-530. Pereira, P., Shang, F., Hobbs, M., Girao, H., Taylor, A. The eye lens has a fully functional ubiquitin pathway. Experimental Eye Research. 2003. v. 76. p. 623-631. BOOK CHAPTERS AND REVIEWS Taylor, A., Warner, J. Physiological function, structure, and mechanism of action of aminopeptidases and aminopeptidase inhibitors. Smith, H.J., Simons, C., Taylor, Francis, N.Y. Proteinase and Peptidase Inhibition: Recent Potential Targets for Drug Development. 2002. p. 305-333. Taylor, A., Hobbs, M. The
2001 Assessment of Nutritional Influences on risk for cataract in Nutrition and Aging. Rosenberg, I., Sastre, A. editors. Karger. 2002. p. 163-192. Brill, E., Patnala, S., Lem, J., Obin, M. Bright Light Induces Retinal degeneration by a Transducin-Independent Mechanism. Holyfield, Anders, LaVail, editors. CRC Press.; Chapter 1-6. 2003. Retinal Degenerations.
Impacts
(N/A)
Publications
- Shang, F., Nowell, T., Gong, X., Smith, D.E., Dallal, G.E., Taylor, A. Sex- linked differences in Cataract Progression in Emory Mice. Experimental Eye Research. 2002. v. 75. p. 109-111.
- Hall, M.O., Obin, M.S., Prieto, A.L., Burgess, B.L., Abrams, T.A. Gas6 binding to photoreceptor outer segments requires '-carboxyglutamic acid (Gla) and Ca2+ and is required for OS phagocytosiis by RPE cells in vitro. Experimental Eye Research. 2002. v. 75. p. 391-400.
- Hao, W., Wenzel, A., Obin, M.S., Chen, C-K., Brill, E., Krasnoperova, N.V., Eversole-Cire, P., Kleyner, Y., Taylor, A., Simon, M.I., Grimm, C., Reme, C.E., Lem, J. Evidence for Two Apoptotic Pathways in light-Induced Retinal Degenerations. Nature Genetics. 2002. v. 32. p. 254-260.
- Brill, E., Patnala, S., Lem, J., Obin, M. Bright Light Induces Retinal degeneration by a Transducin-Independent Mechanism. Holyfield, Anders, LaVail, editors. CRC Press.; Chapter 1-6. 2003. Retinal Degenerations.
- Taylor, A., Jacques, P., Hankinson, S., Willett, W., Rogers, G., Moeller, S., Lu, M., Tung, W., Chylack, L. Risk for progress of early nuclear opacities during 5 years in relation to nutrient intake. Annual Meeting Abstract and Program Planner available from: http://www.arvo.org. Association for Research in Vision and Ophthalmology. 2002. Abstract No. 939.
- Obin, M.S., Lee, B., Thulin, C., Bohm, A., Lee, R.H., Willardson, B.M., Taylor, A. Phosphorylation-dependent binding of phosducin (Pd) to transducin (T) beta-gamma Blocks T gamma ubiquitination catalyzed by ubiquitin (Ub)-conjugating enzyme (Ubc)H5. Annual Meeting Abstract and Program Planner available from: http://www.arvo.org. Association for Research in Vision and Ophthalmology. 2002. Abstract No. 1389.
- Shang, F., Liu, Q., Hobbs, M.L., Taylor, A. Lens fibers have a fully functional ubiquitin-proteasome pathway (UPP). Annual Meeting Abstract and Program Planner available from: http://www.arvo.org. Association for Research in Vision and Ophthalmology. 2002. Abstract No. 466.
- Obin, Y., Lee, B.Y., Meinke, G., Bohm, A., Lee, R.H., Gaudet, R., Hopp, J. A., Arshavsky, V.Y., Willardson, B.M., Taylor, A. Ubiquitilyation of the Transducin ss' Subunit Complex: Regulation by Phosducin. Journal of Biological Chemistry. 2002. v. 277. p. 44566-44575.
- Obin, M.S., Lee, B., Thulin, C., Bohm, A., Lee, R.H., Willardson, B.M., Taylor, A. Transducin (T) beta-gamma ubiquitination: roles of ubiquitin (Ub)-conjugating enzyme (Ubc) H5 and Phosducin (Pd). FASEB Journal. 2002. v. 16(4): Abstract p. A196.
|
Progress 10/01/01 to 09/30/02
Outputs
1. What major problem or issue is being resolved and how are you resolving it? Age-related cataract is a major public health problem. Worldwide it is the major cause of preventable blindness. In the United States approximately 20 and 50 percent of persons 65-74 and 75 years of age, respectively, have age-related cataract which results in visual impairment. Cataract appears in the posterior subcapsular, cortical, and nuclear portions of the eye lens. Age-related maculopathy is a blinding condition involving a degeneration of the retina's macula that is responsible for central vision. There is no surgical cure or treatment for this condition which afflicts approximately 6 percent of the elderly. The compromises in quality of life of our elderly and burden to our health care budgets provide major incentives to explore the etiology of cataract and to discover means to delay cataract onset and/or progression. This CRIS is also determining the extent to which diets rich in
certain foods or nutrients can offer protection against these vision debilities. 2. How serious is the problem? Why does it matter? Cataract afflicts more than half of the aged population. Over $5 billion is spent each year on cataract-related expenses. Delay of cataract formation and/or progression are important public health concerns, since over 1.2 million eye lens extractions are performed annually in the United States. Costs associated with cataract extractions in the United States account for the largest line, 12 percent, of the total Medicare budget. It is estimated that delaying cataract by only 10 years would diminish by 50 percent the number of cataract extractions required. Age- related maculopathy afflicts approximately 6 percent of the elderly. To date there is no surgical cure or treatment for this blinding condition, nor is there a clear path toward the cure. 3. How does it relate to the national Program(s) and National Program Component(s) to which it has been
assigned? This CRIS addresses these goals listed under the National Program 107 - Human Nutrition. Specifically, components "nutrient requirements" and the "relationship between diet, genetics and lifestyle and the risk for chronic disease". This program focuses on the extent to which enhanced levels of intake of various nutrients are associated with risk for age- related retinal degeneration and age-related cataract. 4. What was your most significant accomplishment this past year? A. Single Most Significant Accomplishment during FY 2002: The laboratory continued to conduct the Nutrition and Vision Project - a study that seeks to determine whether and how nutrient intake is related to risk for onset and progression of cataract and age-related maculopathy. With collaborators at Harvard University, scientists gathered lens and retina images and obtained access to the Nurses' Health Study nutrient intake and personal lifestyle databases. Investigators observed that progress of nuclear
cataract is slowed in persons who took vitamin E supplements for more than 10 years. Since it is predicted that a delay of only 10 years would decrease by half the need for cataract extractions, this information would help achieve that objective and provide for enhanced quality of life for the elderly by prolonging their sight without surgery. B. Other Significant Accomplishments: 1. Analysis of information from the Nutrition and Vision Project showed that chances for nuclear cataract are lower in persons with higher abdominal adiposity and that eating according to the USDA Food Guide Pyramid is associated with diminished risk for nuclear cataract. Consuming higher levels of whole grains offered some diminished risk for cataract. Wine drinking is being investigated as a means to alter cataract risk. Correlations are being formulated between eating according to the USDA Food Guide Pyramid and odds for age-related macular degeneration. These accomplishments emphasize the value of the
USDA Food Guide Pyramid as a nutrition guide. 2. It is clear that the accumulation of damaged proteins is partly responsible for cataract formation and age-related macular degeneration. Laboratory scientists are investigating roles for the major protein editing system, called the ubiquitin system, in these diseases. To test hypotheses that the ubiquitin system is involved in removal of damaged proteins, researchers made a mutant ubiquitin, a unique molecule that forms complexes which are not degraded even though part of these complexes contain cellular molecules that should normally be removed. This molecule was used to begin identifying proteins that should be removed in order to avoid disease. Ubiquitin is also involved in the formation of the lens. The laboratory is using these mutants to show how this occurs. These studies are essential in order to harness the power of these tools to maintain lens and retina function and to find dietary means to keep these systems functioning
throughout life. C. Significant Activities that Support Special Target Populations: None. 5. Describe your major accomplishments over the life of the project, including their predicted or actual impact? Cataract and perhaps age-related maculopathy are the major causes of blindness. Health care expenses for the treatment of these conditions account for a substantial part of the public health budget. Studies conducted within this CRIS indicate that not only can the prevalence of these debilities be diminished by appropriate nutrition earlier in life, but also, the amount of public health resources committed to their treatment can be contained if people consume adequate diets. Most importantly, the life quality of the elderly can be enhanced by appropriate nutrient intake early in life. This research is leading to alternative approaches to maintaining lens clarity and retina function. 6. What do you expect to accomplish, year by year, over the next 3 years? Year 1: a) Continue analyses
within the Nutrition and Vision Project; train new investigators to aid in this process b) Correlate alcohol intake, specifically alcohol, wine, hard liquor and beer intake with risk for cataract and macular degeneration c) Determine how ubiquitin conjugating enzyme controls cell division in lens cells d) Establish a new animal (ODS rat) model for cataract Year 2: a) Continue analyses within the Nutrition and Vision Project; train new investigators to aid in this process b) Correlate glycemic index and glycemic load with risk for cataract and macular degeneration c) Determine if there are new pathways by which light damages the retina and if nutrients can protect against that damage d) Show whether vitamin C in the diet can delay cataract in the ODS rat model e) Build a transgenic mouse in which the ubiquitin pathway is altered Year 3: a) Continue analyses within the Nutrition and Vision Project; train new investigators to aid in this process b) Correlate intake of total and specific
fats with risk for cataract and macular degeneration c) Establish new transgenic animal models for age-related macular degeneration d) Use the transgenic mouse in which the ubiquitin pathway is altered to illustrate how lens development was altered and how the pathway can be used to control lens function 7. What technologies have been transferred and to whom? When is the technology likely to become available to the end user (industry, farmer other scientist)? What are the constraints, if known, to the adoption durability of the technology? The laboratory made available to the nutrient/food industry estimates of what supplements should contain as a means to optimize protection of the eye during aging. Investigators have adapted modern techniques in proteomics that are now available for use by other HNRCA scientists. 8. List your most important publications and presentations, and articles written about your work (NOTE: this does not replace your review publications which are listed
below) Ha'aretz (Israeli newspaper) and Ha'aretz Online. March 24, 2002. Davis, J. Vitamin C protects against cataracts: but smoking decreases body's use of antioxidants. http://health.msn.com. February 22, 2002. WB56 television news interview. December 19, 2001.
Impacts
(N/A)
Publications
- Taylor, A., Jacques, P., Hankinson, S., Willett, W., Rogers, G., Moeller, S., Lu, M., Tung, W., Chylack, L. Risk for progress of early nuclear opacities during 5 years in relation to nutrient intake. Annual Meeting Abstract and Program Planner available from: http://www.arvo.org. Association for Research in Vision and Ophthalmology. 2002. Abstract No. 939.
- Obin, M.S., Lee, B., Thulin, C., Bohm, A., Lee, R.H., Willardson, B.M., Taylor, A. Phosphorylation-dependent binding of phosducin (Pd) to transducin(T) beta-gamma Blocks T gamma ubiquitination catalyzed by ubiquitin (Ub)-conjugating enzyme (Ubc)H5. Annual Meeting Abstract and Program Planner available from: http://www.arvo.org. Association for Research in Vision and Ophthalmology. 2002. Abstract No. 1389.
- Shang, F., Liu, Q., Hobbs, M.L., Taylor, A. Lens fibers have a fully functional ubiquitin-proteasome pathway (UPP). Annual Meeting Abstract and Program Planner available from: http://www.arvo. org. Association for Research in Vision and Ophthalmology. 2002. Abstract No. 466.
- Obin, M.S., Lee, B., Thulin, C., Bohm, A., Lee, R.H., Willardson, B.M., Taylor, A. Transducin(T) beta-gamma ubiquitination: roles of ubiquitin (Ub) -conjugating enzyme (Ubc)H5 and Phosducin (Pd). FASEB Journal. 2002. v. 16(4): Abstract p. A196.
- Taylor, A., Jacques, P., Hankinson, S., Willett, W., Rogers, G., Moeller, S., Lu, M., Tung, W., Chylack, L. Progress of early nuclear opacities during 5 years in relation to vitamin supplement use. FASEB Journal. 2002. v. 16(4): Abstract p. A375.
- Shang, F., Deng, G., Nowell, T.R., Taylor, A. K6-modified ubiquitin blocks proteasome binding and inhibits ubiquitin-dependent protein degradation. FASEB Journal. 2002. v. 16(4): Abstract p. A1195.
- Shang, F., Nowell, T., Gong, X., Smith, D.E., Dallal, G.E., Khu, P., Taylor, A. Sex-linked differences in cataract progression in Emory mice. Experimental Eye Research. 2002. v. 75. p. 109-111.
- Taylor, A., Shang, F., Nowell, T., Galanty, Y., Shiloh, Y. Ubiquitination capabilities in response to neocarzinostatin and H(2)O(2) stress in cell lines from patients with ataxia-telangiectasia. Oncogene. 2002. v. 21. p. 4363-4373.
- Weintraub, J.M., Taylor, A., Jacques, P., Willett, W.C., Rosner, B., Colditz, G.A., Chylack, L.T., Hankinson, S.E. Postmenopausal hormone use and lens opacities. Ophthalmic Epidemiology. 2002. v. 9. p. 179-190.
- Shang, F., Gong, X., Egtesadi, S., Meydani, M., Smith, D., Perrone, G., Scott, L., Blumberg, J.B., Taylor, A. Vitamin C prevents hyperbaric oxygen- induced growth retardation and lipid peroxidation and attenuates the oxidation-induced up-regulation of glutathione in guinea pigs. Journal of Nutritional Biochemistry. 2002. v. 13. p. 307-313.
- Taylor, A., Jacques, P.F., Chylack, L.T. Jr, Hankinson, S.E., Khu, P.M., Rogers, G., Friend, J., Tung, W., Wolfe, J.K., Padhye, N., Willett, W.C. Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacities. American Journal of Clinical Nutrition. 2002. v. 75. p. 540-549.
- Shang, F., Deng, G., Obin, M., Wu, C.C., Gong, X., Smith, D., Laursen, R.A. , Andley, U.P., Reddan, J.R., Taylor, A. Ubiquitin-activating enzyme (E1) isoforms in lens epithelial cells: origin of translation, E2 specificity and cellular localization determined with novel site-specific antibodies. Experimental Eye Research. 2001. v. 73(6). p. 827-836.
- Taylor, A., Hobbs, M. 2001 assessment of nutritional influences on risk for cataract. Nutrition. 2001. v. 17(10). p. 845-857.
- Dudek, E.J., Shang, F., Taylor, A. H(2)O(2)-mediated oxidative stress activates NF-kappa B in lens epithelial cells. Free Radical Biology and Medicine. 2001. v. 31. p. 651-658.
- Jacques, P.F., Chylack, L.T. Jr, Hankinson, S.E., Khu, P.M., Rogers, G., Friend, J., Tung, W., Wolfe, J.K., Padhye, N., Willett, W.C., Taylor, A. Long-term nutrient intake and early age-related nuclear lens opacities. Archives of Ophthalmology. 2001. v. 119. p. 1009-1019.
- Taylor, A. Nutrition in vision / cataracts in nurses / cataracts and age- related macular degeneration in physicians. American Academy of Ophthalmology (AAO). Presentation and webcast available from http://www. aao.org November 13, 2001.
|