Some of the brightest minds of their era were totally confounded by human vision. For example, Euclid (of Euclidean geometry) thought that vision was caused by rays emanating from the eyes. Aristotle believed that a form from the object entered the eye. And most believed that perception occurred within the eyes. It took an Arabic polymath named Ibn al-Haytham who wrote a very influential seven-part treatise, Book of Optics, between 1011 to 1021, to explain for the first time that light reflected from an object entered the eye and was perceived in the brain. Al-Haytham may also have understood that the retina was involved in the process of vision.
When you look at an apple, a tree, or the back of your hand, the light scattered from those objects first enters your eye through the cornea and the shutter-like iris, is then focused by the crystallin proteins in the lens, passes all the way through the clear gel-like vitreous humor filling the bulk of the eyeball, and is finally projected upside down on the light-sensing screen at the back of your eye called the retina.
But that’s not the end of the story. Just for kicks, if you’ll humor me, let’s follow the light deeper into the retina itself all the way to the molecule responsible for detecting the photon...
The light now has to pass through multiple layers of neural cells comprising the surface of the retina before coming to the light sensing component of the photoreceptor cell. In the cartoon and microscopy image to the left, light moves from the bottom to the top. Neurons such as ganglions (G in the figure) and bipolar cells (B) and others play a role in pre- and post-processing of light signals that go to the actual photoreceptor cells buried deepest in the retina. The photoreceptors are composed of two types of cells:
· the abundant rods (R) which are active in low-light conditions, are most sensitive to only the blue-green part of the spectrum and therefore do not sense color;
· and the cones (C) which operate best in bright light, are most sensitive to the blue, green and yellow parts of the spectrum, and thus detect color.
In order to capture as much incoming light as possible, rods and cones are packed to fill as much of the usable surface of the retina opposite the lens as possible. This creates a beautiful ordered structure such that the long rod cells are oriented in a single layer and the long axis of the rod is parallel to the incoming light.
The light moves from bottom up again in this cartoon to the left, and after passing the multiple layers of neurons in the retina it finally strikes the rod cell. The dangling rod cells look like the long arms of a jellyfish in this figure which is a bit misleading for purposes of clarity. In reality the rods are packed tightly as can be seen in the previous microscopy image. This cartoon shows a portion of the rod colored red and labeled O or OS (for “outer segment”). This OS is the core functional part for vision as far as we are concerned. The OS is a cylindrical cell compartment that contains thousands of pancake structures or discs. You can see in the previous figure the layer that contains the OS. Adjacent to the OS is the inner segment (I or IS) of each rod cell which is where metabolism occurs, and which is packed with mitochondria. The nucleus (N) is next, finally followed by the long axon and the synaptic terminal (S) shaped like a Hershey’s kiss at the ends. These synapses connect the rod to the bipolar cells (B in the previous figure).
The photon strikes the OS and will finally be captured by one of the light-sensing molecules called rhodopsin on one of the many disks packed in the OS. The disc in the cartoon to the left shows schematically what we came here to see: the rhodopsin proteins embedded within the membrane of the disc. And unlike in the cartoon, these rhodopsin molecules are packed throughout the surface of the disks making up 95% of the protein content of the disc. There are about 25,000 rhodopsin molecules per square micron (millionth of a meter) occupying about half of the disc’s surface area. So… the rhodopsin molecules are packed on the surface of the discs, which are packed in the OS of the rod (and cone) cells, and the rods are packed along the surface of the retina. The goal of this sensor design is to capture every possible bit of light which is important for low-light vision – testing has shown that a rod cell is capable of detecting a single photon.
When the photon is captured by the rhodopsin protein, it is actually absorbed by a molecule called 11-cis retinal (a derivative of vitamin A) which is bound to a specific lysine amino acid within the rhodopsin protein. But before we talk about retinal, let’s pause a bit to talk more about rhodopsin. In the last post, or maybe the one before, I mentioned that transmembrane proteins, proteins that span across a cell’s membrane, are extremely difficult to get x-ray crystallography structures for – because they are just about impossible to crystallize. Well, rhodopsins are a lucky exception. To the left is the first rhodopsin whose structure was determined by Palczewski et al and published in Science in 2000.
And the structure that we see here in that ribbon diagram is of a classic GPCR (G-protein coupled receptor). GPCRs are a very important and large class of receptors encompassing just under a thousand different genes throughout the human genome. Each GPCR binds to a specific signaling molecule. The signal could be a chemical, hormone, lipid, protein or peptide, etc. When a GPCR detects an external stimulus by binding to a molecule it changes shape, much like a switch, triggering a cascade of internal cell signaling events – and that results in some action such as cell division or movement. GPCRs are important targets for cancer research since they are implicated in various steps of tumor growth including cell proliferation, vascular growth, metastasis, etc.
Rhodopsins, and the broader class of proteins they belong to called opsins, and other GPCRs, all contain seven coiled segments that pass back and forth through the cell membrane, like a thread stitched loosely through fabric, and a series of loops on both the extracellular and intracellular sides of the cell membrane which connect the coiled sections. Rhodopsins respond to light as its external signal, as opposed to receiving some chemical signal, since rhodopsins come already bound to its light-sensing retinal ligand.
When light strikes the 11-cis-retinal molecule and is absorbed by it, retinal undergoes a switch-like change in shape as shown here.
The change in shape of the retinal molecule in turn causes a change in the shape of the rhodopsin protein, and this change like other GPCRs is what initiates the signal cascade within the cell.
There!
We followed a photon all the way from some object through the eye all the way down to the specific light-responsive chemical called retinal which is bound within a rhodopsin protein inside a rod cell.
So, briefly, what happens after the photon is absorbed by a retinal molecule?
Rod cells are weird. In the dark, when there are no photons, the rod cell releases neurotransmitter continually. This continuous emission of neurotransmitter is the rod’s normal “off” state (weird, right?). The rod cell’s synapse contacts a bipolar cell, and when the bipolar cell receives the rod’s neurotransmitter, it does NOT release its own neurotransmitter, and is also “off”. The bipolar cell behaves how I (not a neuroscientist) imagine how neurons normally work.
When a photon triggers the rhodopsin molecule, it changes the polarity of the rod cell’s membrane causing it to STOP releasing the neurotransmitter, which is its transient “on” state. When the bipolar cell contacting the activated rod cell stops receiving the rod’s neurotransmitter, the bipolar cell then releases its neurotransmitter and is also “on”… and ultimately we perceive that dim flash of a single photon or an apple in our hand.
Freakin’ cool huh?
NOTE: I always welcome corrections and feedback as I am rambling and meandering far from home on these topics. Any references you could provide are doubly appreciated. Please email me using the “Contact us” form at the bottom of the home or blog pages.
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