Near Infrared Light Reduces Oxidative Stress and Preserves function in CNS Tissue Vulnerable to Secondary Degeneration following Partial Transection of the Optic Nerve Melinda Fitzgerald, 1 Carole A. Bartlett, 1 Sophie C. Payne, 1 Nathan S. Hart, 2 Jenny Rodger, 1 Alan R. Harvey, 3 and Sarah A. Dunlop 1 Abstract Traumatic injury to the central nervous system (CNS) is accompanied by the spreading damage of secondary degeneration, resulting in further loss of neurons and function. Partial transection of the optic nerve (ON) has been used as a model of secondary degeneration, in which axons of retinal ganglion cells in the ventral ON are spared from initial dorsal injury, but are vulnerable to secondary degeneration. We have recently demonstrated that early after partial ON injury, oxidative stress spreads through the ventral ON vulnerable to secondary degeneration via astrocytes, and persists in the nerve in aggregates of cellular debris. In this study, we show that diffuse transcranial irradiation of the injury site with far red to near infrared (NIR) light (WARP 10 LED array, center wavelength 670 nm, irradiance 252 W/m 2 , 30 min exposure), as opposed to perception of light at this wavelength, reduced oxidative stress in areas of the ON vulnerable to secondary degeneration following partial injury. The WARP 10 NIR light treatment also prevented increases in NG-2-immunopositive oligodendrocyte precursor cells (OPCs) that occurred in ventral ON as a result of partial ON transection. Importantly, normal visual function was restored by NIR light treatment with the WARP 10 LED array, as assessed using optokinetic nystagmus and the Y-maze pattern discrimination task. To our knowledge, this is the first demonstration that 670-nm NIR light can reduce oxidative stress and improve function in the CNS following traumatic injury in vivo. Key words: near infrared light; oxidative stress; partial injury; secondary degeneration; vision Introduction T raumatic injury to the central nervous system (CNS) is followed by secondary degenerative changes that result in further loss of neurons and function (Crowe et al., 1997; Farkas and Povlishock, 2007; Khodorov, 2004). Partial tran- section of the optic nerve (ON) is an increasingly useful model of secondary degeneration, in which axons of retinal ganglion cells (RGCs) in the ventral ON are spared from initial dorsal injury, but are vulnerable to secondary degeneration (Fitz- gerald et al., 2009a, 2009b; Levkovitch-Verbin et al., 2003). RGC somata vulnerable to secondary degeneration are lo- cated in the ventral retina, spatially separated from somata whose axons were damaged by the initial primary injury. RGCs succumb to necrosis, and to a lesser extent apoptosis, as a result of secondary degeneration (Fitzgerald et al., 2009b; Levkovitch-Verbin et al., 2009). Oxidative stress is an important contributor to damage following injury to the CNS, and can be modulated by treat- ment with far red to near infrared (NIR) light. We have re- cently demonstrated that the oxidative stress marker manganese superoxide dismutase ( MnSOD) spreads through the ventral ON vulnerable to secondary degeneration via as- trocytes, as early as 5 min after partial ON injury (Fitzgerald et al., 2010), and remains in the nerve in aggregates of cellular debris (Fitzgerald et al., 2009a). MnSOD is a marker of in- creased production of the free radical superoxide, which it catalytically converts to H 2 O 2 . It serves as a general marker for oxidative stress (Aucoin et al., 2005), is associated with RGC death following injury due to excess H 2 O 2 production 1 Experimental and Regenerative Neurosciences, and 2 Neuroecology and Behaviour, School of Animal Biology, and 3 Experimental and Re- generative Neurosciences, School of Anatomy and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia. JOURNAL OF NEUROTRAUMA 27:2107–2119 (November 2010) ª Mary Ann Liebert, Inc. DOI: 10.1089/neu.2010.1426 2107