Macular Degeneration Research - Current Award

	Md Nawajes Mandal, Ph.D. University of Oklahoma Health Sciences Center Oklahoma City, OK Title: Nutritional Supplement Of Phytochemical In Prevention Of AMD Non-Technical Title: Nutraceuticals In Prevention Of AMD Duration: April 1, 2009 - March 31, 2012 Award Type: Standard Award Amount: $100,000
Summary: The efficacy of known potent anti-inflammatory and anti-oxidative botanical compounds such as, curcumin, sulforaphane, and caffeic acid phenethyl ester (CAPE) will be tested in animal models of retinal degeneration. The protective effect of these compounds on cell death will also be tested in cultured retina-derived cells. The mechanism of action of these compounds in retinal protection will be determined. As age-related macular degeneration (AMD) develops from oxidative-stress and chronic inflammation, we hope to find a promising compound that can be tested further in pre-clinical and clinical trials.

Details:

Age-related macular degeneration (AMD) is a multifactorial disease associated with age. It is therefore extremely challenging to develop effective therapies against AMD. Research has identified that oxidative stress and inflammation are integral to the cause, development and effects of AMD. Nutritional supplementation of anti-inflammatory and anti-oxidative compounds holds promises for the least costly and most practical way to delay the onset of AMD and thus protect vision. We have, therefore, selected three botanical compounds which have been in human consumption for hundreds of years as traditional medicines and have been shown to possess potent anti-inflammatory and anti-oxidative properties. As the compounds are plant-derived and non-toxic at fairly high doses, discovering their role in retinal protection will pave the way for clinical trial of a promising compound for augmentative therapy of AMD.

In this project, we will:

1) determine the protective role of curcumin (from Turmeric), sulforaphane (from Broccoli), and caffeic acid phenethyl ester (from Honeybee propolis) in acute and chronic models of light-induced retinal degeneration in rats; and

2) determine the mechanism(s) of curcumin-, sulforaphane-, and caffeic acid phenethyl ester-mediated protection of retina from light-induced damage, and retinal cell lines (661W, ARPE-19) from oxidant-induced damage.

This project will open up new directions for testing the efficacy of other derivatives of these compounds or other promising compounds which may provide better protection from AMD when supplied through diet.

Progress Updates:

In the first year of this grant support, we have determined that dietary supplementation of two plant-derived natural compounds has a protective effect on rat retinas stressed with intense light exposure. A natural compound from cruciferous vegetables (compound 1) showed better protection than a compound from honeybee propolis (compound 2) in this model system.

In order to understand how these compounds exert their protective function, we applied those compounds onto culture plates containing cells that originated from mouse retina. Following this pre-treatment, the cells were exposed to oxidative stress (another source of disease-initiating toxicity). Then, we studied the compounds’ mechanism(s) of action using several biochemical and molecular methods. The experiment on compound 1 is not completed yet. However, when we treated the cells with compound 2, it significantly up-regulated an enzyme protein called “Heme Oxygenase 1,” even without applying a stressor. Heme Oxygenase 1 is a potent defense protein for oxidant and inflammatory stress. Since oxidative stress and inflammation are the root cause of AMD development, a compound that has potential to induce a cellular defense mechanism will have tremendous therapeutic possibilities as a supplement for nutritional and augmentative therapy of AMD.