- Age-related macular
degeneration is a chronic progressive condition and an important cause of
blindness in the elderly characterized by abnormal new vessel growth
- Key compounds of the
major cytochrome P-450 pathway are shown to check abnormal new vessel
growth and prevent blindness in current study
Specific bioactive mediators
of the cytochrome-P450 pathway could influence angiogenesis and prevent
associated blindness in age-related macular degeneration according to a recent
study conducted by Massachusetts Eye and Ear researchers.
The findings of the study appear online in the Proceedings of the
National Academy of Sciences
in August 2017.
‘Targeting the cytochrome-P450 pathway may have therapeutic implications for the treatment of age-related macular degeneration (AMD) as well as other disorders involving abnormal new vessel growth.’
Targeting Immune Cells In
AMD Treatment - An Option Largely Overlooked Age-related macular degeneration
nearly 11 million Americans and nearly 200 million persons globally with the
figures expected to double by 2020. The risk of developing AMD is nearly 30
percent after 75 years of age.
AMD has been the focus of several research projects but the role of
immune cells in the regulation of angiogenesis in AMD and other disorders has
largely been ignored in earlier studies.
The current team embarked on this study to determine the possible role
of immune cells in angiogenesis and to look for newer and possibly safer and
more cost-effective therapeutic options in managing AMD.
Role Of Immune Cells In
Angiogenesis In AMD - The Study
The team conducted their study on preclinical animal
models. The notable findings of their study were the following
- Key compounds of the cytochrome-P450, a major enzyme pathway may
influence angiogenesis and control movement of inflammatory cells to the
- Specifically, the team identified two key bioactive lipid
mediators generated from the CYP pathway namely 17,18-epoxyeicosatetraenoic acid (EEQ) and
19,20-epoxydocosapentaenoic acid (EDP).
- The above two compounds were found to protect animal models of the
disease from forming abnormal new vessels (angiogenesis).
The findings of the study seem to suggest that targeting the cytochrome-P450 pathway could have important therapeutic
implications in the treatment of AMD and other inflammatory conditions
characterized by angiogenesis
(including cancer) by
increasing the expression of these lipid mediators.
"Given the high prevalence and progressive nature of neovascular
eye disease, the ability to stabilize bioactive lipids that mitigate or halt
disease is of great and increasingly therapeutic significance," said
corresponding author Kip Connor, Ph.D., a vision scientist at Mass.
Eye and Ear and Assistant Professor of Ophthalmology at Harvard Medical
School. "It is our hope that emerging technologies and future studies will
expand on our work, and ultimately lead to safe, targeted, and cost-effective
therapies that markedly improve visual outcomes and quality of life for
patients suffering from these debilitating eye diseases."
Mechanism of Action of EEQ
and EDP - More Effective in AMD?
The ω-3 long-chain polyunsaturated fatty acids are a class of dietary
lipids found abundantly in the central nervous system and the retina. In
general the ω-3s have anti-inflammatory properties and particularly, 17,18- epoxyeicosatetraenoic acid
and 19,20- epoxydocosapentaenoic acid, metabolites of the CYP pathway were
shown by liquid chromatography-tandem MS and found to protect against
The current standard of care for persons with wet AMD is based on
targeting VEGF, an agent that promotes angiogenesis. Although VEGF inhibitors reduce angiogenesis and vascular
permeability, there is no disease resolution
or complete vessel regression.
Studies in mouse models of wet
AMD have shown that Cytochrome P-450 derived EEQ and EDP promote resolution of
disease, as well as aid in vascular repair and regression.
Age Related Macular
Degeneration - In Brief
AMD is a leading cause of blindness in the elderly. In the advanced
stages of the disease, termed 'wet' or neovascular AMD, there is growth of
abnormal new blood vessels on the surface of the retina (the light sensitive
structure at the back of the eye responsible for vision).
The abnormal angiogenesis occurs in around 10-15 percent of AMD
patients, and progresses rapidly ultimately leading to blindness.
Several treatments are available to treat AMD including angiogenesis
Scope Of Current Study
The current study has identified a probable immune/inflammatory
mechanism of angiogenesis prevention that can be further explored in future
research with potential therapeutic implications of this debilitating
"Although we do not fully understand how and why AMD develops,
identifying additional mechanisms that regulate abnormal blood vessel growth in
the eye beyond what we currently know could open up a range of possibilities
for new research and treatments for AMD," Dr. Connor said.
- Cytochrome P450-generated metabolites derived from-3 fatty acids attenuate neovascularization - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4084420/)