Visible light modulation of mitochondrial function in hypoxia and disease

Abstract

The present invention provides methods of using electromagnetic radiation in the visible portion of the spectrum to modulate mitochondrial function in the treatment of various conditions, including Alzheimer's disease, other dementias, hypoxia and diabetic peripheral neuropathy, and sensory disorders of the extremities.

Description

RELATED APPLICATIONS[0001]This application claims priority benefit of U.S. Provisional Patent Application Ser. No. 60 / 917,385; filed May 11, 2007 and of U.S. Provisional Patent Application Ser. No. 61 / 012,300, filed Dec. 7, 2007, the disclosures of which are incorporated herein in their entirety.BACKGROUND OF THE INVENTION[0002]Photobiomodulation, using light emitting diode (LEDs) arrays or low energy lasers, has been reported to have a variety of therapeutic benefits (Conlan et al. 1996; Sommer et al. 2001; Whelan et al. 2001; Yu et al. 1997; Delellis et al. 2005; Powell et al. 2004; Harkless et al. 2006; Powell et al. 2006). This non-invasive therapy has been used to accelerate wound healing, improve recovery rates from ischemia, slow degeneration of injured optic nerves, and improve sensitivity and reduce pain in various types of peripheral neuropathies including those associated with diabetes.[0003]Diabetes is a common metabolic disorder that is rapidly becoming an epidemic worl...

AI Technical Summary

Benefits of technology

[0009]Accordingly, in a first aspect the invention provides a method of treating hypoxia in a tissue of a mammalian subject by exposing the hypoxic tissue of the mammal to electromagnetic radiation. Exposure to the radiation improves tissue blood flow in the hypoxic state by increasing the production of NO thereby reducing vascular resistance in the tissue. Accordingly, in one embodiment, the invention provides a method of preventing or repairing tissue damage in a hypoxic tissue by exposing the tissue to electromagnetic radiation. In related embodiments, the invention provides methods of increasing mitochondrial nitrite reductase activity or NO production in the exposed tissue by exposing the tissue to electromagnetic radiation. In some embodiments, the invention provides an in vivo or in vitro method of modulating NO production by neurons or endothelial cells in a mammalian tissue capable of producing NO under hypoxic conditions and / or high concentrations of glucose by cytochrome c nitrite reductase activity by exposing the neurons or endothelial cells to the radiation. In another embodiment, the invention relates to combination therapy of electromagnetic radiation with a second agent (e.g, nitrite, NO donors, nitroglycerin, organic nitrites, arginine) which promotes NO activity in reducing vascular resistance. In preferred embodiments, of any of the above, the radiation is in the visible portion of the electromagnetic radiation spectrum.

[0010]In a second aspect, the invention provides a method of improving energy metabolism in a hypoxic tissue by exposing the tissue to electromagnetic radiation. The exposure to electromagnetic radiation alters cytochrome C oxidase or the phosphorylation of cytochrome c oxidase in such a way as to modulate its nitrite reductase activity. Additionally, the electromagnetic radiation exposure leads to the increased expression of mitochondrial proteins leading to an increase in mitochondrial biogenesis in the tissue. In some related embodiments, the invention provides a method of modulating respiration mediated by cytochrome c oxidase in a cell of a tissue or of modulating the phosphorylation of cytochrome c oxidase in a cell of a tissue by exposing the tissue to electromagnetic radiation. In some embodiments, the amount or expression of one or more subunits selected from the group of subunits of cytochrome c oxidase, cytochrome c, cytochrome c reductase or ATP synthetase in the tissue is increased.

Problems solved by technology

They are a major cause of pain associated with diabetes and often result in lower extremity amputations.

However, under some pathological conditions (Poyton, 1999) they are released and can either act destructively (to induce oxidative stress, a condition that lies at the heart of many diseases as well as aging), or constructively (in intracellular signaling pathways (Poyton and McEwen, 1996)).

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