First of all, I’d like to apologize for the long wait between blog posts. Things have been a bit hectic for the SFM team, but that’s no excuse for leaving our readers & backers hanging.
In a previous post, we summarized some of the ways by which the human body obtains, transports, stores, and utilizes retinoids, collectively referred to as vitamin A. In this post, we’ll be discussing in more depth the ways retinol/retinal is used in human vision, and a means to metabolically hack this process using vitamin A2–the focus of our current research project.
The Human Visual System
The first thing one needs to understand in order to understand the NIR vision project is that color is, quite literally, all in our heads. What we call “color” is actually our perception of different wavelengths of light. In point of fact, apples are not red. Apples have no color, because color is not a physical property. Apples appear red because other physical and chemical characteristics cause them to interact with white light in such a way that they reflect red light (electromagnetic radiation on the long end of the visual spectrum) most strongly (to our perception).
Human vision works via a process called phototransduction. Transduction essentially means a process whereby an organ of the body translates external stimuli into electrical signals the brain can interpret. Transduction occurs in the ear, when vibration of cochlear hairs is translated into electricity, which we then perceive as sound. It occurs in the fingertips, when lamellar are disturbed and translate that into electricity, which we then perceive as texture, pressure, or vibration. And it occurs in the eye, when electromagnetic radiation of just the right wavelength strikes the retina, and we see the world around us.
The human visual spectrum comprises radiation of wavelengths from approximately 390nm-700nm in length. This is a minute range, and represents less than an estimated 1% of 1% of the entire EM spectrum.
On the retina, there are structures called rods and cones. Rods and cones contain protein complexes called photopigments, which are the agents of phototransduction. These photopigments, when struck by light of the correct wavelength, electrochemically stimulate the optic nerve, which feeds into the brain, resulting in what we call vision.
These photopigments are the focus of our entire project. They are, as an engineer would say, the primary bottleneck for the entire system. Two types of pigments are produced and utilized in the human eye: rhodopsin in the rods, which can be thought of as the brightness & contrast sensory opsin, and photopsin in the cones, which grants us sharp color vision. These pigments respond only to the aforementioned human visual spectrum of approximately 390-700nm. Both of these pigments are formed by an opsin protein in the eye and retinal, a derivative of retinol, or vitamin A.
George Wald
In 1939, however, an important discovery was made in the field of vision science. George Wald, the man acclaimed for first identifying the role of vitamin A in vision, had discovered a new photopigment. In his paper “The Porphyropsin Visual System”, Wald describes a pigment used by freshwater fish that was formed of opsin and 3,4-dehydroretinal, rather than retinal. He called 3,4-dehydroretinol vitamin A2, and the pigment porphyropsin. Since then a variety of animals have been shown to use this pigment to some degree–besides fish, crustaceans, amphibians, and possibly some reptiles.
Porphyropsin responds to radiation with longer wavelengths than the human photopsin & rhodopsin, extending to approximately 950nm in the near infrared range.
Research has indicated that humans may be able to utilize this exotic photopigment. Multiple mammalian studies, primarily involving rodents, have shown varying degrees of success. The reason for this appears to be the similarity between the molecules retinol and 3,4-dehydroretinol.
The addition of an ethylene group in the polyene chain of the latter molecule poses little difficulty when it comes to bonding with human opsins. The major hurdle in this project is the 3-4x greater bioactivity of vitamin A relative to vitamin A2 in the human body. Essentially, the various cellular systems involved in storing, transporting, and using retinoids prefer vitamin A over vitamin A2. From an evolutionary standpoint, this makes sense, as retinoic acid–perhaps the most vital retinoid for human survival–has not been successfully synthesized from vitamin A2 (hence why the project entails retinoic acid supplementation). Current research suggests that the body’s strong affinity for vitamin A may be a result of what is called competitive inhibition, which can be thought of essentially as strength in numbers. It is also possible that certain intracellular transport mechanisms have their own specific affinity for vitamin A. In either case, our current project entails taking vitamin A almost completely out of the picture, via adoption of a vitamin A deficient diet.
In the next blog post, Jeff will be explaining the design and function of our stimulator device. In combination with the electroretinography equipment discussed in a previous post, this device will allow us to precisely measure any shifts in the visual spectrum for the duration of this experiment. Thanks for reading!