Effect of NASA Light-Emitting Diode Irradiation on Molecular Changes for Wound Healing in Diabetic Mice HARRY T. WHELAN, M.D., 1 ELLEN V. BUCHMANN, B.S., 1 APSARA DHOKALIA, Ph.D., 2 MARY P. KANE, B.S., 1 NOEL T. WHELAN, B.S., 1 MARGARET T.T. WONG-RILEY, Ph.D., 3 JANIS T. EELLS, Ph.D., 4 LISA J. GOULD, M.D., Ph.D., 5 RASHA HAMMAMIEH, Ph.D., 2 RINA DAS, Ph.D., 2 and MARTI JETT, Ph.D. 2 ABSTRACT Objective: The purpose of this study was to assess the changes in gene expression of near-infrared light ther- apy in a model of impaired wound healing. Background Data: Light-Emitting Diodes (LED), originally devel- oped for NASA plant growth experiments in space, show promise for delivering light deep into tissues of the body to promote wound healing and human tissue growth. In this paper we present the effects of LED treat- ment on wounds in a genetically diabetic mouse model. Materials and Methods: Polyvinyl acetal (PVA) sponges were subcutaneously implanted in the dorsum of BKS.Cg-m +/+ Lepr db mice. LED treatments were given once daily, and at the sacrifice day, the sponges, incision line and skin over the sponges were harvested and used for RNA extraction. The RNA was subsequently analyzed by cDNA array. Results: Our studies have revealed certain tissue regenerating genes that were significantly upregulated upon LED treatment when compared to the untreated sample. Integrins, laminin, gap junction proteins, and kinesin superfamily motor proteins are some of the genes involved during regeneration process. These are some of the genes that were identified upon gene array experiments with RNA isolated from sponges from the wound site in mouse with LED treatment. Conclusion: We believe that the use of NASA light-emitting diodes (LED) for light therapy will greatly enhance the natural wound healing process, and more quickly return the patient to a pre- injury/illness level of activity. This work is supported and managed through the Defense Advanced Research Projects Agency (DARPA) and NASA Marshall Space Flight Center–SBIR Program. 67 INTRODUCTION T HE NEED TO CARE for a population with chronic wounds is a growing challenge that requires innovative approaches. One approach that specifically addresses the identified patho- physiological processes involved in wound healing is light therapy. We believe that the use of NASA light-emitting diodes (LED) for light therapy will greatly enhance the natural wound healing process. This will save valuable time and re- sources for both patients and health care facilities. Further- more, improved wound healing will reduce the risk of infection for the patient, decrease the amount of costly dress- ings required, and more quickly return the patient to a pre- injury/illness level of activity. Laser light has been widely acclaimed to speed wound heal- ing of ischemic, hypoxic, and infected wounds. 1 Lasers pro- vide low energy stimulation of tissues that results in increased cellular activity during wound healing. 2,3 These activities in- clude collagen production and angiogenesis. 4 Wound healing has three phases: first a substrate is laid down, then cells proliferate, and finally there is remodeling of tissue. The data published so far suggests that laser biostimula- tion produces its primary effect during the cell proliferation phase of the wound healing process. It has been demonstrated that mitochondria are receptive to monochromatic near- infrared light and that laser light likely increases respiratory metabolism of certain cells. 2,3,5 Processes such as fibroblast proliferation, attachment and synthesis of collagen and pro- 1 Department of Neurology, Medical College of Wisconsin, Milwaukee, Wisconsin. 2 Department of Molecular Pathology, Walter Reed Army Institute of Research, Silver Spring, Maryland. 3 Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin. 4 Department of Pharmacology, Medical College of Wisconsin, Milwaukee, Wisconsin. 5 Department of Plastic Surgery, University of Texas Medical Branch, Galveston, Texas. Journal of Clinical Laser Medicine & Surgery Volume 21, Number 2, 2003 © Mary Ann Liebert, Inc. Pp. 67–74