According to the medical literature, numerous garlic-derived organosulfer compounds are known to cause a variety of biological effects, including decreases in blood cholesterol level and platelet aggregation in patients with hyperlipoproteinemia, and suppression of systolic and diastolic blood pressure in hypertensive humans. However, the sites and mechanisms of action of specific compounds from garlic responsible for these biological effects are poorly understood. Research in this laboratory has revealed that topically administered garlic compounds (allicin and S- allylmercaptocysteine) lowered intraocular pressure in rabbits. To understand the ocular action of these organosulfer compounds in garlic, the mechanisms of lower intraocular pressure effects will be examined using in vivo and in vitro approaches. The long-term objectives of this research are to: 1) determine the sites of action whereby aqueous humor inflow and outflow are regulated by organosulfur compounds and 2) elucidate the cellular mechanisms for the ocular hypotension induced by garlic compounds. The hypothesis to be tested is that garlic compounds (allicin and S-allylmercaptocysteine) lower intraocular pressure by modifying aqueous inflow and/or outflow through alterations in cellular function in the iris-ciliary body (inflow) and trabecular mesh (outflow).
The specific aims will be to: 1) characterize effects in vivo on aqueous humor dynamics (intraocular pressure, aqueous inflow and outflow facility) and 2) determine sites and mechanisms of action in the anterior segment by evaluating the biological effects of garlic compounds on tissues and cells that regulate aqueous inflow and outflow. Although the medicinal value of garlic has been proposed, the potential efficacy of garlic derivatives for glaucoma therapy has not been determined. The goal of this pilot research project will be to provide evidence for the significance of garlic to traditional and more specifically to define the potential role of garlic compounds in modulating ocular hydrodynamics. This research should provide significant leads to the discovery of novel therapeutic agents for the treatment of chronic, open-angle glaucoma, the principal cause of blindness in African Americans.

Project Start
1998-08-01
Project End
1999-07-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
12
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Morehouse School of Medicine
Department
Type
DUNS #
City
Atlanta
State
GA
Country
United States
Zip Code
30310
Wilson, Nana O; Solomon, Wesley; Anderson, Leonard et al. (2013) Pharmacologic inhibition of CXCL10 in combination with anti-malarial therapy eliminates mortality associated with murine model of cerebral malaria. PLoS One 8:e60898
Igietseme, Joseph U; Omosun, Yusuf; Partin, James et al. (2013) Prevention of Chlamydia-induced infertility by inhibition of local caspase activity. J Infect Dis 207:1095-104
Wilson, Nana; Driss, Adel; Solomon, Wesley et al. (2013) CXCL10 gene promoter polymorphism -1447A>G correlates with plasma CXCL10 levels and is associated with male susceptibility to cerebral malaria. PLoS One 8:e81329
Kim, Teayoun; Zhelyabovska, Olga; Liu, Jian et al. (2013) Generation of an inducible, cardiomyocyte-specific transgenic mouse model with PPAR ?/? overexpression. Methods Mol Biol 952:57-65
Liu, Mingli; Amodu, Audu S; Pitts, Sidney et al. (2012) Heme mediated STAT3 activation in severe malaria. PLoS One 7:e34280
Wilson, Nana O; Ceesay, Fatou K; Hibbert, Jacqueline M et al. (2012) Pregnancy outcomes among patients with sickle cell disease at Korle-Bu Teaching Hospital, Accra, Ghana: retrospective cohort study. Am J Trop Med Hyg 86:936-42
Shelton, Martin N; Huang, Ming-Bo; Ali, Syed A et al. (2012) Secretion modification region-derived peptide disrupts HIV-1 Nef's interaction with mortalin and blocks virus and Nef exosome release. J Virol 86:406-19
Campbell, Patrick E; Isayev, Olexandr; Ali, Syed A et al. (2012) Validation of a novel secretion modification region (SMR) of HIV-1 Nef using cohort sequence analysis and molecular modeling. J Mol Model 18:4603-13
Wilson, Nana O; Ceesay, Fatou K; Obed, Samuel A et al. (2011) Intermittent preventive treatment with sulfadoxine-pyrimethamine against malaria and anemia in pregnant women. Am J Trop Med Hyg 85:12-21
Lucchi, Naomi W; Jain, Vidhan; Wilson, Nana O et al. (2011) Potential serological biomarkers of cerebral malaria. Dis Markers 31:327-35

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