0 0 Photobiomodulation The Healing Power of Light Janis T. Eells, Ph.D. Wisconsin Distinguished Professor

1 1 Thank You for the Opportunity to Share Our Work WiSys and M. John UW Stout

2 2 Colleagues and Collaborators  Harry Whelan  Margaret Wong-Riley  Michele Henry  Ellen Buchmann  Jonathan Stone  Krisztina Valter  Diana Kirk  Jim VerHoeve  Mike Nork  Janis Eells  Kristina DeSmet  Sandeep Gopalakrishan  Ron Ignatius  Judy Ignatius  Robin Schumacher  Alfredo Sadun  Rina Das  Marti Jett  Solange Salomao  Adriana Berezovsky

3 3 Photobiomodulation Change in Function by Light EXAMPLES Photosynthesis Vit D Activation Rhodopsin activation in Vision

4 4 The Leap from Plants to Animals Light stimulates photoacceptor molecules in plant cells and in animal cells. Plant cells chloroplasts contain chlorophylls and other photoacceptors phytochromes, cryptochromes Animal cells - cytochrome c oxidase (mitochondria), hemoglobin, myoglobin, porphyrin compounds.

5 5 From Growing Plants on the Space Shuttle to Treating Mouth Ulcers in Cancer Patients NASA funded the development of LEDs for use in Plant Growth Experiments on the Space Shuttle and International Space station –QDI and Wisconsin Center for Space Automation and Robotics Shown to improve healing in animal models of diabetic wound healing Used to improve healing of Mucositis in Bone Marrow Transplant Patients

6 6 Photobiomodulation Postulated Signaling Pathway

7 7 Photobiomodulation Activation of Mitochondrial Cytochrome Oxidase

8 8 Why Cytochrome Oxidase Correlation of Absorption Spectrum with Action Spectrum

9 9 Photobiomodulation Why Cytochrome Oxidase? Cytochrome Oxidase absorbs light at the NIR wavelengths which promote cell division, cell repair and cell metabolism Key mitochondrial enzyme Important Regulator of Cell Function Cell Signal Transducer

10 Why Mitochondria ?  Produce Energy - ATP  Side Product - ROS  Signal other parts of cell  Regulate Life and Death of the Cell -”nature’s ultimate clock”

11 Mitochondrial Dysfunction Plays An Important Role in Cellular Aging and Degenerative Diseases Cardiovascular Disease Eye Diseases - Macular Degeneration, Glaucoma Neurodegenerative Diseases - Parkinson’s Disease Skeletal Muscle - Aging and Injury Metabolic Diseases - Diabetes Environmental Toxins - TCDD

12 Photobiomodulation for Laser Induced Retinal Damage Healed Functional Retina Pilot Lased Damaged Retina Persistence in Combat Low Level Energy Therapy Integrated into Face Sheild and Helmet of Pilot

13 Photobiomodulation Promotes Retinal Healing Following Laser Eye Injury

14 Methanol Intoxication: Models Aging and Retinal Disease by poisoning retinal mitochondria Ingestion of a small amount (1- 2 oz) of methanol can produce permanent blindness. Methanol is metabolized to a mitochondrial toxin, formic acid which acts to inhibit Cytochrome Oxidase. Formic acid disrupts mitochondrial function in the retina and optic nerve resulting in blindness.

15 Photobiomodulation for Retinal Disease

16 Photobiomodulation Attenuates Methanol Toxicity Protects Against Loss of Retinal Function 670 nm Treatment At 5 hr, 25hr, 50 hr 28 mW/cm min 4 joules/cm 2

17 Photobiomodulation Attenuates Methanol Toxicity Prevents Retinal Damage

18 Retinitis Pigmentosa is a Retinal Degenerative Disease Characterized by Photoreceptor Death A majority of RP cases result from a mutation in the rhodopsin gene Leading to misfolded opsin. Misfolded opsin increases oxidative stress and leads to photoreceptor cell death

19 Will Photobiomodulation Attenuate Photoreceptor Cell Death Retinits Pigmentosa? Time Course of Photoreceptor Death in the P23H-3 and SD Retina

20 Photobiomodulation maintained or upregulated cytochrome oxidase activity in the inner segments of photoreceptors.

21 Photobiomodulation reduced the rate of photoreceptor death during the critical period:

22 Photobiomodulation Applications Eye Diseases - Macular Degeneration, Glaucoma, Diabetic Retinopathy Neurodegenerative Diseases - Parkinson’s Disease, ALS, Alzheimers Disease, MS Skeletal Muscle - Aging and Injury Metabolic Diseases - Diabetes Environmental Toxins

23 Acknowledgement of Support