Progress 11/01/07 to 10/31/12
Outputs OUTPUTS: Several activities were conducted during this project to help reach the goals and objectives of our research project to reduce eye inflammation. These activities included a variety of laboratory experiments examining the role of dietary components in regulating cellular inflammation. Understanding the molecular mechanisms by which dietary components influence cellular inflammation is a primary thrust of this project and our laboratory. Results have been disseminated at national meetings, in published reports and via popular press articles PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Results from research outlined in this proposal are designed to provide information related to the role of diet in the development of cataracts. Understanding the benefit of dietary antioxidants in preventing disease may benefit the general population, especially those at greater risk for cataract development (elderly). The development of cellular models to study cataractogenesis may benefit those basic scientists interested in using in vitro tools to study this disease. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts Research in our laboratories is aimed at understanding how diet can impact vision. Specifically we are interested in elucidating mechanisms by which dietary pigments, known as carotenoids, can reduce risk for the development of cataracts. Age-related cataracts are a leading cause of visual impairment and blindness among the elderly in the United States. Current treatment for cataract involves surgical extraction, an expensive procedure that is performed over 1.5 million times annually in the United States alone. The costs of health care and poor quality of life associated with this disease argue strongly that further research to define its causes is needed. Our laboratory has taken on a series of studies to examine how two plant pigments, lutein and zeaxanthin, reduce the risk for the development of cataract. From these experiments we have characterized how lutein and zeaxanthin are taken up into the lens of the eye and how they can reduce damage caused by ultraviolet radiation. These findings have been disseminated at national meetings, in published reports and via popular press articles.
Publications
- Long AC, Agler A, Colitz CM, Zhang J, Hayek MG, Failla ML, Bomser JA. Isolation and characterization of primary canine lens epithelial cells. Vet Ophthalmol. 2008 Jan-Feb;11(1):38-42.
- Long AC, Colitz CM, Bomser JA. Regulation of gap junction intercellular communication in primary canine lens epithelial cells: role of protein kinase C. Curr Eye Res. 2007 Mar;32(3):223-31.
- Chitchumroonchokchai C, Bomser JA, Glamm JE, Failla ML Xanthophylls and alpha-tocopherol decrease UVB induced lipid peroxidation and stress signaling in human lens epithelial cells. J Nutr. 2004 Dec;134(12):3225-32.
- Long AC, Colitz CM, Bomser JA Apoptotic and necrotic mechanisms of stress-induced human lens epithelial cell death. Exp Biol Med (Maywood). 2004 Nov;229(10):1072-80.
- Boileau T, Bray T, and Bomser JA (2003) Ultraviolet radiation modulates nuclear factor kappa B activation in human lens epithelial cells. J Biochem Mol Toxicol. 17(2):108-13.
- Glamm JE, Chitchumroonchokchai C, Bomser JA and Failla M (2003) Use of cyclodextrin as a vehicle for loading human lens epithelial and human ciliary body cells with xanthophylls and alpha-tocopherol. FASEB J 17(5):A758-A758.
- Bomser, J.A. (2002) Ultraviolet radiation selectively induces mitogen-activated protein kinase cascades in Human lens epithelial cells. J. Biochem Mol. Toxicol.
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Progress 01/01/11 to 12/31/11
Outputs OUTPUTS: Several activities were conducted this past year to help reach the goals and objectives of our research project to reduce eye inflammation. These activities included a variety of laboratory experiments examining the role of dietary components in regulating cellular inflammation. Understanding the molecular mechanisms by which dietary components influence cellular inflammation is a primary thrust of this project and our laboratory. Results have been disseminated at national meetings, in published reports and via popular press articles. PARTICIPANTS: In addition to the PI's, collaborating participants include: Dr. Heather Chandler,Assistant Professor. College of Optometry, The Ohio State University. TARGET AUDIENCES: TARGET AUDIENCES: Our research has potential benefits to persons at risk for cataract, basic scientists, optometrists, ophthalmologists, farmers involved in growing carotenoid-rich fruits and vegetables, general public interested in improving their health. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts The 1.2 million cataract surgeries performed in the United States this year will cost taxpayers over $3.0 billion dollars in health care. Delaying the onset, reducing the severity and/or preventing the development of cataracts will not only improve the quality of life of our aging population but also significantly reduce health care costs associated with this disease. We anticipate that data from our research will provide insight into the mechanisms by which dietary components can modulate cataract formation and encourage the consumption of foods that provide protection against cataractogenesis.
Publications
- No publications reported this period
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Progress 01/01/10 to 12/31/10
Outputs OUTPUTS: Several activities were conducted this past year to help reach the goals and objectives of our research project to reduce cataractogenesis. These activities included a variety of laboratory experiments examining the role of retinoic acid in regulating how lens epithelial cells communicate with each other. Understanding the molecular mechanisms by which dietary components influence lens cell communication is a primary thrust of this project. Our project is designed to elucidate mechanisms by which dietary components can influence ocular health. Several of our findings have been reported in popular press magazines and websites. In addition, our findings have been presented at several national scientific meetings (Experimental Biology, Association for Research in Vision and Ophthalmology) and universities (University of Florida, Purdue University and University of North Dakota Medical School). PARTICIPANTS: In addition to the PI's, collaborating participants include: Dr. Heather Chandler,Assistant Professor. College of Optometry, The Ohio State University. Dr. Deborah Gryzbowski, Assistant Professor, Havener Eye Institute, The Ohio State University. TARGET AUDIENCES: Our research has potential benefits to persons at risk for cataract, basic scientists, optometrists, ophthalmologists, farmers involved in growing carotenoid-rich fruits and vegetables, general public interested in improving their health. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts The 1.2 million cataract surgeries performed in the United States this year will cost taxpayers over $3.0 billion dollars in health care. Delaying the onset, reducing the severity and/or preventing the development of cataracts will not only improve the quality of life of our aging population but also significantly reduce health care costs associated with this disease. We anticipate that data from our research will provide insight into the mechanisms by which dietary components can modulate cataract formation and encourage the consumption of foods that provide protection against cataractogenesis.
Publications
- No publications reported this period
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Progress 01/01/09 to 12/31/09
Outputs OUTPUTS: Several activities were conducted this past year to help reach the goals and objectives of our research project to reduce cataractogenesis. These activities included a variety of laboratory experiments examining the role of retinoic acid in regulating how lens epithelial cells communicate with each other. Results from these experiments will be presented by a co-collaborator on this project, Dr. Heather Chandler at our quarterly nutrition symposium at The Ohio State University. Understanding the molecular mechanisms by which dietary components influence lens cell communication is a primary thrust of this project. PARTICIPANTS: Dr. Heather Chandler,Assistant Professor. College of Optometry, The Ohio State University. Dr. Deborah Gryzbowski, Assistant Professor, Havener Eye Institute, The Ohio State University. TARGET AUDIENCES: Our project is designed to elucidate mechanisms by which dietary components can influence ocular health. Several of our findings have been reported in popular press magazines and websites. In addition, our findings have been presented at several national scientific meetings (Experimental Biology, Association for Research in Vision and Ophthalmology) and universities (University of Florida, Purdue University and University of North Dakota Medical School). PROJECT MODIFICATIONS: Not relevant to this project.
Impacts The 1.2 million cataract surgeries performed in the United States this year will cost taxpayers over $3.0 billion dollars in health care. Delaying the onset, reducing the severity and/or preventing the development of cataracts will not only improve the quality of life of our aging population but also significantly reduce health care costs associated with this disease. We anticipate that data from our research will provide insight into the mechanisms by which dietary components can modulate cataract formation and encourage the consumption of foods that provide protection against cataractogenesis.
Publications
- Long, AC. Grzybowski D., Bomser JA. Chandler H. (2010) All-trans retinoic acid regulates Cx43 expression, gap junction communication and differentiation in primary lens epithelial cells. Current Eye Research. Accepted for publication
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Progress 01/01/08 to 12/31/08
Outputs OUTPUTS: Lutein is a plant pigment in the carotenoid family that participates in the light harvesting activity required for the process of photosynthesis and filters "blue" light (450 nM) that can damage proteins, DNA and membranes in plants. Plant foods such as spinach and kale are important sources of lutein for humans. It has been shown that lutein and its related oxycarotenoid, zeaxanthin, are selectively accumulated in both the human lens and the macula region of the retina. Epidemiological studies suggest that the risk of developing cataracts in human lens and age-related macula degeneration (AMD) is inversely proportional to dietary intake, as well as plasma levels, of lutein and zeaxanthin. Moreover, the amounts of lutein and zeaxanthin in these ocular tissues are significantly decreased with cataract and AMD. These associations and the well established antioxidant properties of the carotenoids have led to the proposal that lutein and zeaxanthin protect eyes against the damaging effects of ultraviolet (UV) radiation and oxidative stress. Numerous supplements are now commercially available and manufacturers of multivitamin and mineral pills also have included lutein in the formulation and boldly inform the consumer that the compound will protect their eyes. Direct evidence to support such claims is lacking. Our laboratory has conducted several in vitro and in vivo studies examining the role of carotenoids and other dietary antioxidants in modulating cellular events associated with stress-signaling in the lens of the eye. In addition, our work has focused on the furthe development and characterization of a primary canine lens epithelial cell system that may be useful in studying cataractogenesis in vitro. PARTICIPANTS: Dr Carmen Colitz Veterinary Hospital 601 Vernon Tharp St Columbus, OH 43210 Phone: (614) 292-3551 Email: colitz.1@osu.edu Dr. Mark Failla 150A ARPS 1945 N HIGH STREET COLUMBUS, OH 43210 +1 614 247 2412 TARGET AUDIENCES: Results from research outlined in this proposal are designed to provide information related to the role of diet in the development of cataracts. Understanding the benefit of dietary antioxidants in preventing disease may benefit the general population, especially those at greater risk for cataract development (elderly). The development of cellular models to study cataractogenesis may benefit those basic scientists interested in using in vitro tools to study this disease. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts Our project has had several significant outcomes. First, we have successfully characterized the cellular growth and differentiation of a primary canine lens epithelial cell system. Once characterized, this cell line may serve as a useful tool in studying cataract formation in both canines and humans. Second, our cellular work has established a role for the regulatory protein kinase C in mediating gap junction communication in canine lens cells. Because disruptions in lens cell gap junction communication can contribute cataract formation, understanding the cellular mechanism involved in this process may lead to therapeutic strategies to reduce this disease.
Publications
- Long AC, Agler A, Colitz CM, Zhang J, Hayek MG, Failla ML, Bomser JA. Isolation and characterization of primary canine lens epithelial cells. Vet Ophthalmol. 2008 Jan-Feb;11(1):38-42.
- Long AC, Colitz CM, Bomser JA. Regulation of gap junction intercellular communication in primary canine lens epithelial cells: role of protein kinase C. Curr Eye Res. 2007 Mar;32(3):223-31.
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Progress 01/01/06 to 12/31/06
Outputs Cataracts are a major problem for many middle aged, pure breed species of dogs. The Iams Company is a major producer of high-end foods for companion animals. During the 1990s, investigators at Iams demonstrated that lutein enhanced the competency of the immune system in dogs. Lutein is now included in their formulations and the statement that their products strengthen immunity is central to the marketing efforts. This proposal will test the hypothesis that lutein and zeaxanthin can protect canine lens and retinal cells against UV and oxidative insults in vitro. Additional antioxidants (i.e. rosmarinic and caffeic acid) present in Iams pet food formulations will also be examined for their ability to protect against ocular disease. The physiological significance of these treatments will be examined. The long term objective of our collaborative research project is to determine the roles of dietary lutein (LUT) and zeaxanthin (ZEA) in protection of lens and the retina
against UV-induced stress and establish the physiological relevance of these compounds in maintaining canine ocular health. It has been approximately one year since our first dog was recruited for participation in the lutein study. Since this time, approximately one dog / month has been recruited (n=13). Unfortunately, two of these dogs did not return for cataract surgery and four dogs did not consistently consume provided biscuits. These confounding factors have hindered study progress and our ability to collect an adequate sample size. Despite these obstacles, recruitment efforts continue, with the most recent canine surgery completed on 6/14/07. Further discussion is needed to establish timelines for completion and possible study modifications (i.e. sample size). In addition to our continued efforts with lutein feeding trial, research characterizing dog lens epithelial cell growth and differentiation has been completed. A manuscript reporting these data has been prepared and is
ready for submission following approval from involved parties.
Impacts The 1.2 million cataract surgeries performed in the United States this year will cost taxpayers over $3.0 billion dollars in health care. Delaying the onset, reducing the severity and/or preventing the development of cataracts will not only improve the quality of life of our aging population but also significantly reduce health care costs associated with this disease. We anticipate that data from our research will encourage the consumption of foods that provide protection against cataractogenesis.
Publications
- Long AC, Colitz CM, Bomser JA. Regulation of gap junction intercellular communication in primary canine lens epithelial cells: role of protein kinase C. Curr Eye Res. 2007 Mar;32(3):223-31.
- Long AC; Agler A; Colitz CMH; Zhang J; Hayek M; Failla ML; Bomser JA. Isolation and characterization of primary canine lens epithelial cells. Vet Ophthal. 2007(in review)
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Progress 01/01/05 to 12/31/05
Outputs Understanding the molecular mechanisms by which dietary factors (i.e. carotenoids) influence ocular health is a primary focus of this laboratory. Sepcifically, research efforts during the past year have examined the role of dietary carotenoids on gap junction communication (GJC) in the lens epithelium. GJC is the primary mechanism by which nutrients and other important molecules are transported in the lens. With age, GJC decreases in the lens and this decreased activity may be associated with cataract development. Our laboratory has preliminary data suggesting that lutein, a dietary carotenoid that selectively accumulates in the lens, can up-regulated GJC in this tissue; suggesting a potential role of this carotenoid in protecting against age-related cataract. These data will be presented at the Association for Research in Vision and Opthalmology (ARVO) meeting in Spring 2006.
Impacts The 1.2 million cataract surgeries performed in the United States this year will cost taxpayers over $3.0 billion dollars in health care. Delaying the onset, reducing the severity and/or preventing the development of cataracts will not only improve the quality of life of our aging population but also significantly reduce health care costs associated with this disease. We anticipate that data from our research will encourage the consumption of foods that provide protection against cataractogenesis.
Publications
- Colitz CM, Bomser JA, Kusewitt DF. The endogenous and exogenous mechanisms for protection from ultraviolet irradiation in the lens. Int Ophthalmol Clin. 2005 Winter;45(1):141-55. Review.
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Progress 01/01/04 to 12/31/04
Outputs Research continues examing the protective effects of antioxidants, specifically lutein and zeaxanthin, in reducting oxidative damage associated with cataract development. We have recently demonstrated that lutein and zeaxanthin reduce oxidant-induced damage in human and canine lens epithelial cells. Interestingly, lutein and zeaxanthin were signficantly more effective than vitamin E in preventing oxidant-induced damage in the lens epitehlium. Future studies are designed to elucidate the cellular and molecular mechanisms by which antioxidants provide protection against oxidative stress in the lens. Funding proposals to the USDA and relevant industry partners have been submitted with decisions expected by April 2005.
Impacts The 1.2 million cataract surgeries performed in the United States this year will cost taxpayers over $3.0 billion dollars in health care. Delaying the onset, reducing the severity and/or preventing the development of cataracts will not only improve the quality of life of our aging population but also significantly reduce health care costs associated with this disease. We anticipate that data from our research will encourage the consumption of foods that provide protection against cataractogenesis.
Publications
- Chitchumroonchokchai C, Bomser JA, Glamm JE, Failla ML Xanthophylls and alpha-tocopherol decrease UVB induced lipid peroxidation and stress signaling in human lens epithelial cells. J Nutr. 2004 Dec;134(12):3225-32.
- Long AC, Colitz CM, Bomser JA Apoptotic and necrotic mechanisms of stress-induced human lens epithelial cell death. Exp Biol Med (Maywood). 2004 Nov;229(10):1072-80.
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Progress 01/01/03 to 12/31/03
Outputs Our laboratory has recently demonstrated that lutein and zeaxanthin, two dietary carotenoids that selectively accumulate in the lens of the eye, can inhibit ultraviolet light induced lens damage. Specifically, lutein and zeaxanthin decreased ultraviolet-light induced activation of JNK, a stress protein associated with lens epithelial cell death. In addition these dietary carotenoids also decreased ultraviolet light induced lipid peroxidation in the lens.
Impacts The 1.2 million cataract surgeries performed in the United States this year will cost taxpayers over $3.0 billion dollars in health care. Delaying the onset, reducing the severity and/or preventing the development of cataracts will not only improve the quality of life of our aging population but also significantly reduce health care costs associated with this disease. We anticipate that data from our research will encourage the consumption of foods that provide protection against cataractogenesis.
Publications
- Boileau T, Bray T, and Bomser JA (2003) Ultraviolet radiation modulates nuclear factor kappa B activation in human lens epithelial cells. J Biochem Mol Toxicol. 17(2):108-13.
- Glamm JE, Chitchumroonchokchai C, Bomser JA and Failla M (2003) Use of cyclodextrin as a vehicle for loading human lens epithelial and human ciliary body cells with xanthophylls and alpha-tocopherol. FASEB J 17(5):A758-A758.
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Progress 01/01/02 to 12/31/02
Outputs Information about the mechanism of the selective accumulation of lutein (LUT) and zeaxanthin (ZEA) by the avascular lens and macular tissues, as well as the specific roles of xanthophylls in these tissues, is limited. Here, water soluble complexes of either LUT, ZEA or a-tocopherol (alpha-TC) with methyl-beta-cyclodextrin were prepared for in vitro delivery of the lipophiles to human lens epithelial cells (HLE) and non-pigmented human ciliary body cells (CB). The lipophiles were efficiently incorporated into cyclodextrin and the complexes remained stable for at least 6 months at -80C. Cellular concentrations of LUT, ZEA and alpha-TC increased in a dose dependent manner when cultures of HLE and CB cells were incubated in medium containing either 0.25-1.5 uM LUT or ZEA and 0-40 uM alpha-TC for as long as 6 hours. The concentrations of accumulated lipophiles in HLE cells were relatively stable for 24 h after loading. Exposure of HLE cells to UV radiation (300 Joules/cm2)
induced lipid peroxidation in control cells. Similar treatment of HLE cells after loading with either LUT or alpha-TC protected the cells against UV-induced lipid peroxidation and slightly decreased the cellular concentration of the lipophiles. These data support a the protective influence role of LUT and alpha-TC against UV-induced damage to the lens epithelium.
Impacts The 1.2 million cataract surgeries performed in the United States this year will cost taxpayers over $3.0 billion dollars in health care. Delaying the onset, reducing the severity and/or preventing the development of cataracts will not only improve the quality of life of our aging population but also significantly reduce health care costs associated with this disease. We anticipate that data from our research will encourage the consumption of foods that provide protection against cataractogenesis.
Publications
- Boileau, T., Bray, TM. and Bomser JA. (2003) UVA radiation modulates nuclear factor kappa B (NFkB) activity in human lens epithelial cells. J. Biochem Mol. Toxicol.
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Progress 01/01/01 to 12/31/01
Outputs Our laboratory has made significant progress in understanding the impact of ultraviolet radiation on human lens epithelial cell signaling. Specifically, we have demonstrated that ultraviolet radiation activates stress signaling patways within the lens of the eye. This activation may play an important role in the development of cataracts. In collaboration with Dr. Mark Failla (Chair, Human Nutrition and Food Management) we have succesfully introduced the carotenoid lutein into lens epithelial cells. This will allow us to measure the importance of this carotenoid in protecting against ultraviolet-induced lens damage.
Impacts The role of diet in preventing eye disease is currently one of the most important topics in the area of nutrition and food science. Our acquistion of a human lens epithelial cell line will allow us to continue to answer fundamental questions on the role of dietary carotenoids in maintaining eye health.
Publications
- Bomser, J.A. (2002, in press) Ultraviolet radiation selectively induces mitogen-activated protein kinase cascades in Human lens epithelial cells. J. Biochem Mol. Toxicol.
- T.W.-M. Boileau, Tammy M. Bray and J.A. Bomser (2002) UVA radiation modulates nuclear factor kappa B (NFkB) activity in human lens epithelial cells. . Dept. Human Nutrition and Dept. Food Science and Technology, The Ohio State University, Columbus, OH 43210. FASEB Meeting, New Orleans, LA.
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