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Visible light modulation of mitochondrial function in hypoxia and disease

a technology of mitochondrial function and visible light, applied in the field of visible light modulation of mitochondrial function in hypoxia and disease, can solve the problems of lower extremity amputation, achieve the effects of promoting phosphorylation or conversion, reducing the level or production of reactive oxygen species, and no production

Inactive Publication Date: 2010-12-30
CLARIMEDIX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes the use of visible electromagnetic radiation to improve blood flow, reduce vascular resistance, and increase NO production in hypoxic tissue. The radiation can also modulate the function of cytochrome c oxidase, which is involved in the production of NO. The invention provides methods for treating various conditions related to hypoxia, oxidative stress, and diabetes by exposing the tissue to electromagnetic radiation. The effects of the radiation can be measured by measuring the levels of NO, VEGF, or protein carbonylation. The invention also provides methods for monitoring the effect of electromagnetic radiation treatment on tissue blood flow and blood glucose levels.

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)).

Method used

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  • Visible light modulation of mitochondrial function in hypoxia and disease
  • Visible light modulation of mitochondrial function in hypoxia and disease
  • Visible light modulation of mitochondrial function in hypoxia and disease

Examples

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example 1

Role of the Respiratory Chain in No Production in Endothelial Cells Under Hypoxic Conditions

[0086]Currently, there are two known pathways for NO synthesis. The first involves nitric oxide synthase (NOS), an enzyme that converts arginine to citrulline in the presence of NADPH and oxygen. There are three isoforms of nitric oxide syththase (NOS). These are designated NOS I (neuronal NOS), NOS II (inducible NOS), and NOS III (endothelial NOS). The second pathway for NO production involves nitrite-dependent NO production by the mitochondrial respiratory chain. This pathway is active only at reduced oxygen concentrations.

[0087]The relative importance of the NOS-dependent and NOS-independent NO synthesis in endothelial cells is assessed before and after visible light treatment. The production of NO is evaluated in cells exposed to hypoxic conditions in the presence of physiological concentration of nitrite. The involvement of the respiratory chain in this process is evaluated in the presen...

example 2

NO Production by Endothelial or Cells

[0088]Endothelial cells are isolated and cultured as described elsewhere (Wang et al., 2007; Wang et al., 2004). Hypoxia (1.5% O2, 93.5% N2, 5% CO2) or anoxia (5% CO2, 4% H2, 91% N2) is established in an IN VIVO workstation (Biotrace) or Coy laboratories glove box, pre-equilibrated with the appropriate gas mixture. All cell extracts are prepared inside the workstation or glove box to prevent re-oxygenation. Cells are maintained under anoxic or hypoxic conditions for varying lengths of time (2-8 hr). Nitric oxide production is evaluated with the fluorescent nitric oxide indicator DAF-FM (Molecular Probes, CA). Nutrient media are supplemented with 20 μM NaNO2. The involvement of the respiratory chain in nitrite dependent NO production is evaluated in the presence of: a) the inhibitors of complex III Antimycin A (10μM), myxothiazol (10 μM) and Cyanide (1 mM); b) disruptors of the mitochondrial membrane potential FCCP (10 μM) and dinitrophenol (100 μ...

example 3

Mitochondrial Functionality And NO Production

[0089]Mitochondria from normal and hypoxic cells is isolated and evaluated for respiratory control, hypoxic production of nitrite dependent NO production, and production of nitrite dependent NO production after incubation with ATP and theophylline, using methods described previously (Castello et al, 2006).

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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...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61N5/06C12N13/00C12Q1/02A61K49/00A61P43/00
CPCA61N5/0613A61N2005/0644A61N2005/0647A61N5/0622A61N2005/0662A61N2005/067A61N2005/0652A61P43/00A61N5/067
Inventor DUNNING, JOHNDULLIEN, VIVIANPOYTON, ROBERT O.MURDOCH, RICHARD SAMUEL
Owner CLARIMEDIX
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