# The Potential of Visible and Far-Red to Near-Infrared Light in Glaucoma Neuroprotection
## 3 Pathophysiology of Glaucoma: Increased IOP, Mitochondrial Dysfunction, and Altered Ion Fluxes
Indeed, apoptotic caspases -3, -8, and -9 are cleaved in RGC after a period of elevated IOP, and inflammatory caspases -1, -4, and -12 are also upregulated [37]. Visible and Far-Red to Near-Infrared Photobiomodulation in RGCs in Mitochondrial Protection and Energy Metabolism  
The major goal of basic and translational research is to enhance the viability of RGCs in order to maintain their function [29]. Various strategies targeting mitochondrial protection provide a promising way to delay the onset of glaucoma or protect RGCs against glaucomatous damage, as mitochondria play an important role in the pathogenesis of primary open-angle glaucoma [8]. Specifically, experimental studies have shown that the light of different wavelengths can directly affect oxidative phosphorylation in a wavelength-specific manner when it is absorbed by mitochondrial chromophores [29]. Indeed, some studies have shown that RGCs possess a high number of mitochondria and are sensitive to the exposure of visual red light (680-900 nm), which has been reported to be absorbed by cytochrome-c oxidase (COX), a key enzymatic complex for cell bioenergetics, especially nerve cells in the retina and brain. COX contains four redox metal centers, Cu\({}_{\text{A}}\), Cu\({}_{\text{B}}\), Hem a, and Hem a\({}_{3}\), where electrons are transferred sequentially; different light wavelengths determine peaks of absorption for the complex: 620 nm (range 613.5-623.5 nm), 825 nm (range 812.5-846 nm), 760 nm (range 750.7-772.3 nm), and 680 nm (range 667.5-683.7 nm), which correspond to Cu\({}_{\text{A}}\) reduced, Cu\({}_{\text{A}}\) oxidized, Cu\({}_{\text{B}}\) reduced, and Cu\({}_{\text{B}}\) oxidized, respectively. In neural tissue, COX is the most abundant metalloprotein complex, and its exposure to light at 670 nm and 830 nm correlates highly with its peaks in catalytic activity, as well as with ATP content in animal models in vitro [38]. ROS and NO, which are among the secondary mediators of PBM, are able to activate signaling pathways and transcription factors [39], demonstrating that redox equilibrium is important in the physiology of cells; it is also central in pathological events due to the ability of ROS to activate or inactivate various proteins, receptors, ions, and other signaling molecules. Notably, many cellular signaling pathways are perturbed, leading to cellular dysfunction and, subsequently, the development of various pathologies, among which are eye diseases; this occurs when the redox equilibrium is disturbed due to the excessive accumulation or depletion of ROS. In this context, PBM may also function by increasing the bioavailability of NO by prompting its release from intracellular stores, such as heme-containing proteins under normoxic conditions. Since NO functions as an inhibitor of mitochondrial respiration, its dissociation from cytochrome C oxidase would restore mitochondria's oxygen consumption which, in turn, should increase energy production and boost cellular metabolism [10]. Thus, it is currently accepted that red light enhances the mitochondrial function, thereby improving mitochondrial energy metabolism and the consequent increase in mitochondrial membrane potential (\(\Delta\)Y) and proton gradient (\(\Delta\)pH). Therefore, red light exerts a cytoprotective function by preventing apoptotic cell death, as demonstrated in animal models in vivo [14; 26] and, consequently, it can reduce the damage caused by a variety of conditions studied in animal models in vivo [9; 40; 41; 42]. The successful attenuation of histopathological changes in animal retina in situ [34; 39; 40; 42; 43; 44] is supported by the clinical use of far-red to near-infrared (FR/NIR) therapy to enhance mitochondrial function.