So that’s kind of where we are today and now to understand how light can actually affect cellular physiology, we have to dive into a little bit of a cellular mechanism. There’s something called a chromophore that exists inside of most species, bacteria included, most eukaryotes. What chromophores do is they are actually specialised portions of the cell that are responsible for absorbing photons. So light is packets of photons and we have to have some way to biologically accept those things. We know of a couple really common ones if we all think about it, melanin in our skin melanin is a chromophore. So when ultraviolet lights hits our melanin we have a chemical reaction that comes that creates pigmentation and we start tanning. So this does exist. It also exists in plants. Chlorophyll is a type of chromophore as well. It accepts sunlight and creates a cellular mechanism inside of that plant. Well there’s two different types of chromophore as you have specialised and non-specialised. The specialised ones you’re using right now which. We have rods and cones inside of our eyes and allow us to accept photons. You see down there in the middle we have three different types of cones in our eyes. We have red, we have greens, and we have blues. That allows us to see the visual spectrum. What’s interesting is these chromophore either absorb or reflect different wavelengths of light. So at the bottom we see that the red chromophore and our cones accepts the lights at 560 nanometers and it rejects or reflects everything else, so that we can see red when those chromophore are stimulated. Green, 530. Blue, 430. So we see the number starts to decrease as we go towards the blue end of the spectrum where the ultraviolet end of the spectrum. As the numbers start to get higher as far as the wavelength, as we go towards the infrared or microwave. Now speaking of microwaves, microwave is just a continuation of the electromagnetic spectrum. One of the things that we see with microwaves is anytime you put a piece of food in the microwave, what happens to the food as you turn it on? It heats! Does it on the outside? No, it heats all the way through even if it’s in a container. So microwaves can penetrate different types of aspects. So when we start a little moving a little bit further up that spectrum towards the ultraviolet spectrum, we should also assume that those wavelengths that are longer can also penetrate like microwaves can. So that’s something we should start thinking in the back of our mind. So we also started to see on the right side of the screen, we have some of the different cells that are in our eyes, some of them are photo acceptors which are the types that don’t have any participation in senses. And we have photoreceptors so photoreceptors talk about phototransduction and when we start looking at receptor-based therapies we always say that receptors have one job. They are transducers. They take some sort of a physical energy and they convert it into electrical energy so that we can experience the world in which we exist. So the phototransduction occurs in the receptors and then the photobiomodulation occurs in the photo acceptors. Receptors versus acceptors. So when we start really getting into this electron transport chain there is a target of photobiomodulation. This is Cytochrome c oxidase. So Cytochrome c oxidase, when we start looking at the electron transport chain has a really really important role in mitochondrial function. It’s the last stage in reduction in the mitochondrial transport electron transport chain before we can produce ATP. So when we say when light hits Cytochrome c oxidase what it does is it implements the complex 4 of the mitochondrial transport chain. What that does is that takes hydrogen molecules and also we start looking at O2 molecules which are super oxide molecules and converts them into water. When it converts that into water inside the medic mitochondrial matrix, what it does is it releases hydrogen protons into the extracellular space. Well when we start looking, that’s the first thing that happens is when light shines on this on this Cytochrome c oxidase it creates hydrogen molecules and as those hydrogen molecules start to increase in their numbers we can see there is an influx into complex five which the end result is ATP. We all know that ATP is super important for what? Life. For energy. However, we also know that free hydrogen molecules are not also the best thing for us either. So in an electron transport chain we’re going to see that there’s going to be release of network oxide, which as Dr. Jay was just talking about, is really important for vasoconstriction and dilation regulation or vasoregulation, I should say. But we also know that nitric oxide can have detrimental effects on cellular function as well, because it can actually block Cytochrome c oxidase.
So some of the research thinks the reason why we have this sharp drop off curve with a laser therapy or photobiomodulation is because you may exceed the metabolic capacity of the mitochondria, which is a term that we’ve been talking about for quite a while. The other thing that happens is we also have an elevation of temperature. Elevation of temperatures is anything in the realm of one tenth of one degree Celsius, has a big change in intracellular pressure. So you start having more changes in sodium potassium transduction and things of that nature. We also know that some of our cells have thermoreceptors or temperature gated channels that can allow influx or outflux of ions. So we have those primary effects of this photobiomodulation, then we start looking at secondary effects. There are many many many. There’s a little bit of a diagram on the side there and you can kind of go through that but realistically what ends up happening is protein kinase has become set into place which creates the release of calcium and cyclic amp which are signalling molecules. Nitric oxide as well as the reactive oxygen species that are produced by the electron transport chain are cellular molecules that signal for cellular processes to occur. Everything from immune activation with some of the reactive oxygen species we start activating superoxide dismutase which is a really strong antioxidant that promotes cellular health. But we also see that these secondary messengers also activate different types of metabolic pathways not on a mitochondrial layer, but on a nuclear layer such as transcription, translation and protein production for cellular health. There is also tertiary effects of photobiomodulation We see here in the bottom right hand corner,this is from a paper published by Hamblin and right now from what I’ve been able to read Hamblin seems to be one of the authorities in this area. One of our colleagues here today has a great poster presentation that he did with Hamblin. Dr Hamblin works at Mass General Hospital, Harvard trained, and they have a whole department on photobiomodulation there at Harvard. He is one of the main people in charge of this and what he found is that the tertiary responses to photobiomodulation mean that you increase more blood vascularization, angiogenesis, synaptogenesis which is a huge interest to us, right? We talked about superoxide dismutase upregulation and NF-kB, are big anti-inflammatory cytokines, get produced. We have up regulation of mesenchymal stem cells which can differentiate in neural tissue. They can be created into fibroblasts for collagen and muscle tissue. Lots of changes that happen. We have increased lymphatic drainage. Then we get the dissociation of nitric oxide. So we produce it then we dissociate it, so it’s not such a harmful chemical because at certain points the concentrations in nitric oxide can also change membrane potentials. We also see increased blood flow. So you see there’s primary, secondary and tertiary, and then there are systemic effects. So before I talk about the systemic effects there is a great study that was published by Johnstone done in 2014. They were a little bit skeptical of this transcranial stimulation. So what they did is they took a bunch of rodents, MPTP rodents. So these are rodents that they genetically and experimentally induced Parkinson’s disease with. What they did, and I couldn’t find a good picture of it, is that they put tinfoil hats on the rats, almost like the people from outer space are coming for them right? So they put tinfoil hats on them so that the light cannot penetrate the tinfoil and affect their brain but they shine the light on their body. What they realize in their controlled study is that the ones that had the lights that shined on their brain had the best results with some of their task speed and walking speed and maze test, but the ones that had their head covered with the aluminum foil also had significant improvements over the controls. So this leads a little more to question right what are the systemic effects of photobiomodulation at ulterior sites. The place where they actually shined the light on these rodents was actually on the tibia. So they shined it on their tibia. It wasn’t on their spinal cord, it wasn’t anywhere in the nervous system. It’s on their actual tibia. So some of the effects of photobiomodulation cannot be explained entirely by photons penetrating the skull and accessing brain tissue. However what they have shown is that in 2003, the calvarial bone has really high levels of mesenchymal stem cells that exist inside there. So maybe there is some photo activation of mesenchymal stem cells. They also showed in 2011 with Andrew that the effects can last days to weeks, and potentially even months after the stimulation stops. So there are systemic long term effects that happen there.