#ocular posting

[justkidneying]

Albinism

Albinism is a disease that causes a defect in the normal synthesis or transport of melanin. There are a couple different types, but the main distinction is the difference between oculocutaneous albinism (OCA) and ocular albinism.

Oculocutaneous Albinism

OCA is caused by an autosomal recessive mutation. There are seven different mutations that can cause albinism, though OCA1 to 4 are the common ones (with OCA2 being the most common). All of these different mutations affect the melanin pathway (the chemical reaction steps to turn phenylalanine into melanin).

OCA1 is caused by a mutation in the tyrosinase gene, which causes a lack of an enzyme in the melanin production pathway. There are actually two types of OCA1, with one having no tyrosinase, and the other having reduced tyrosinase. OCA1 is the most extreme form of albinism, which gives a person very pale skin, white hair, and light eyes.

The OCA2 gene (located on chromosome 15) encodes for the P protein, which is a transporter of a melanin precursor. This gene also has a large role in the color of iris a person will have. Those with OCA2 will have light skin, lighter brown or blond hair, and light colored eyes.

So basically, someone with a defect in either one of the transporters or enzymes of the pathway will not be able to have their melanocytes produce normal melanin. This leads to pale skin, white hair, and light-colored eyes (but it is a spectrum depending on the exact type).

Ocular Albinism

Ocular albinism is an X-linked mutation (a portion of the X chromosome is mutated). This means it affects males more than females. It causes loss of pigmentation in the iris. OA1 is the most common, and is associated with uncontrolled eye movements. OA2 is associated with color and night blindness. There is also a third type that is associated with deafness, but sometimes that also happens with OA1.

A fun fact: there is a type of albinism that only affects non-human animals called leucism. This leads to a partial loss of pigmentation that affects the hair, scales, feathers, and skin of the animal, but not the eyes. You can see this in white lions that have normally-colored eyes and noses.

Albinism and Eyesight

Now onto the role melanin plays in eye function. Albino people have poor eyesight as a result of their melanin deficiencies. But why? We're going to have to go into some eye stuff to answer this question.

So your retina has two parts: temporal and nasal (two halves, one closer to your temple and one closer to your nose). The input from each half is processed with the opposite half from the other eye. I have another post that explains this better. So, the optic nerves meet at the optic chiasm, with some fibers staying on the same side, and other fibers crossing over. Mammals with forward-facing eyes have larger temporal retina than mammals with lateral-facing eyes (like a guinea pig). About half of the optic fibers also remain uncrossed at the chiasm because of this.

Most people with albinism have almost all of their fibers cross at the chiasm, which is essentially a misrouting of very important sensory information. The eye structure is also changed with albinism, as most albino people have poorly formed fovea (the depression in the center of the retina where vision is the sharpest). They also have more blood supply than normal to the foveal area (it is supposed to be avascular). The retinal macula is usually poorly developed and there is a reduction in cone density (what allows you to see color).

Stereovision is also impaired, which is the ability to discern three-dimensional information about objects using the difference between the inputs from each eye. Those with albinism are also more likely to have nystagmus (involuntary eye movement) and strabismus (crossed eyes).

Albinism and Hearing

Now, onto the ear. The eye and ear are very intimately connected. The ear lets the eye know where to look for threats. This means that the visual and auditory spaces within the brain interact. Fun fact: when blind people are asked to localize sounds, the visual cortex is more engaged than the auditory cortex. Albino animals have fewer binaural cells, and more difficulty visually locating the source of sounds. A lot of the stuff related to this goes beyond the scope of what I want to explain here, but just understand that melanin is important for the development of both the auditory and visual systems of the brain.

Albinism and Immune Function

Finally, I want to discuss the immune system. Melanocytes are important cells for immune function, and release a lot of immune-promoting factors. For some reason, a lot of people think of those with albinism as having weak immune systems or being sickly. If you'll notice what I said earlier about the cause of albinism, it is a lack of transporters or enzymes in the melanin pathway. Not the lack of melanocytes. People with albinism still have these cells, it is only their ability to produce melanin that is impaired.

However, there are immune conditions that affect melanocytes, such as Chediak-Higashi syndrome. This is an autosomal recessive disorder that affects lysosomal trafficking proteins, and causes lysosomal function to be impaired. People with this disease will have frequent infections, platelet function impairment, as well as albinism. This means that albinism does not cause immune deficiency, but is a symptom of conditions that also affect the immune system.

[justkidneying]

Why Changing Your Eye Color is Stupid as Shit

I'm back to ocular posting, but that's because I just read an article about a lady who went blind because she wanted blue eyes.

Eye Color

This is all due to the stroma of the iris. Everyone has a back portion of the iris called the iris pigment epithelium that's brown and helps block light. The front layer is the stroma, which can have a range of melanin in it, giving us a color between blue and brown.

Why it's bad to fuck with it

Your eyes are special sensory organs, and probably our favorite ones at that. We use a lot of our brain to process visual stimuli, so there's scientific evidence that humans like to see. They're also delicate. You can clog up the drains in them (glaucoma) and go blind, you can detach the retina and go blind, etc. There's a lot of ways to go blind when we're just talking about the ball itself.

How these procedures do it

There's two main surgeries to change eye color: laser and implant. Laser procedures use a laser to destroy the stroma. I hope you can appreciate how bad that is. It can damage the eye itself, or the particles of pigment it dissolves can clog up your drains.

Implant surgeries look like garabge for one, but the main issue is that you're in a country with less regulation to get some silicone implanted into your eye so it can look weird. This can cause infection and blindness. And it just gives me the heebie jeebs to thing about.

I personally just don't think this looks great...

(note that this surgery could be helpful for those who have lost part of their iris, but we're only talking about cosmetics here)

A disease that can change eye color

This one is just for fun. I enjoy studying Fuch's heterochromic iridocyclitis, so I'm going to tell you about it. This disease causes glaucoma, cataracts, loss of visual acuity, and most noticeably, loss of eye pigmentation. Usually, it affects one eye, causing heterochromia. It usually makes the eye look almost flakey, and can have several patterns of effect. Look up some pictures if you're interested. I've attatched one below, showing the normal eye on the left and the affected eye on the right. The person will end up with a blue/gray eye color as their pigmentation is lost.

A Final Note

It's so weird that all these people want like blue or green eyes. Why? Most humans (and mammals) have brown eyes because they are the best at blocking light. People with lighter eyes are usually more sensitive to bright lights. And besides, it doesn't even matter. I honestly can't even tell you what color eyes my friends have. No one is going to think you are super extra special and cool because you have aquamarine eyes. I promise you, no one cares enough about your eyes for you to go blind trying to change them.

[justkidneying]

Farsightedness vs. Nearsightedness

A lot of people are farsighted (hyperopic) or nearsighted (myopic), though many more people are myopic (about 40-50% of US adults). Hyperopia is the inability to focus on objects that are near to you, and myopia is the inability to focus on objects that are far away.

First, we need to discuss what a lens is. A lens is a clear object which refracts and focuses light. This will take an image that is in front of the lens and make an image behind the lens (in this case, on your retina). An important concept is the lens equation (1/o + 1/i = 1/f). o is the object distance from the lens, i is the image distance from the lens, and f is the focal length. The focal length is the distance from the lens to the focal point, where the sharpest image is produces. You want this to be on the retina.

Your eye has little tiny muscles in it (called ciliary muscles) that contract to change the shape of the lens. This is done because you cannot change the distance to the object or image, only the focal length (which is related to the radius of the curvature of the lens). You do this subconsciously in order to create a crisp image of whatever you want to focus on (isn't that neat?!). The ciliary muscles contract (as part of the accommodation triad) when you want to read something up close, allowing the lens to return to its normal shape.

People with farsightedness (hyperopia) have eyes that are too short for their lens. This means that even when their ciliary muscles have contracted and their lens is allowed to return to its fullest shape, the image is still focused behind the retina.

People with nearsightedness (myopia) have an eyeball that is too long. This means that even when their lens is fully tensed and thinned by the fibers around it, the image is still focused in front of the retina.

So how do we fix this? Well, you can do it with glasses and contacts, which act as a second lens so that the light that hits your biological lens is then refracted to hit your retina. We can also fix this surgically with LASIK and PRK. LASIK is a surgery where a flap of your cornea is cut off and then the tissue beneath it is thinned out. Then the flap is put back. This may not be the best option for people who have a thinner cornea or need a higher degree of correction. PRK is simpler, in that your cornea isn't cut, just reshaped with a laser. It has a longer healing time but is a good option for people with a higher degree of correction needed.

[justkidneying]

Motion Sickness

I've had the wonderful experience of sitting next to my sister on a plane, who never fails to bring her ginger ale back to light of day just as we land. It made me wonder why some people get nauseous in cars, planes, boats, etc. So, I'm going to explain how the vestibular system works, how it integrates with your ocular input, and why this makes some people feel sick.

The Vestibular System

This is the system within the inner ear consisting of the otolith organs (utricle and saccule) and the semicircular canals (there's three of those). It sits next to your cochlea within the inner ear, and the same cranial nerve (CN VIII) innervates both of them.

The semicircular canals detect the three planes of head rotation (yes, no, and ear to ear movements). The utricle senses movement in the horizontal plane, and the saccule senses it in the vertical plane (like the force of gravity). They each have these little plates of hair cells and some rocks on top of a gelatinous mass (it's true, look it up) that move to polarize or depolarize cells as their direction changes.

The Integration of Vestibular and Ocular Information

CN VII heads to the brainstem, where it enters through the pontomedullary junction. From there, it projects through the inferior cerebellar peduncle to the flocculonodular lobes of the cerebellum, or to the vestibular nuclei (of which there are four). From there, the information is used to determine head position, and make the appropriate neck, core, limb, and eye corrections to maintain balance.

Within the cerebellum, vestibulo-ocular information is organized and acted upon. You also get some positional information from your eyes. These systems are pretty well connected. Let's see what happens when they don't match up.

Motion Sickness

When you are in a car, your vestibular system can detect acceleration (same thing on a boat or plane), however, the objects in front of you aren't moving. This gives your brain two different signals, one that you are moving and one that you aren't. This is also why people with car sickness shouldn't try to read and should look out the window, it gives their eyes movement signals to send.

The opposite is true with people who get sick from VR head sets or video games. Their eyes are sending that they are moving, and their vestibular system senses no motion. This is confusing for the brain.

Why This Happens

There are a few theories, and some are more ass than others. I'll go from least stupid to most stupid. The one we learn in medical school is that the conflicting signals are just confusing for the brain, and this makes you feel sick. Simple as that. Your vestibular system can get used to constant velocity (and you can overcome seasickness if you became a sailor), so this answer isn't totally great. But it works.

There is also an anticipation component. That would be why a driver would experience less motion sickness than a passenger. In my mind, they're also usually looking ahead and seeing the car move, not fiddling with Spotify on their phone (hopefully) so that could be part of it too.

Another theory is that the sensations produced are similar to the feeling we get from toxic substances (which are detected by the area postrema, which makes us vomit), so our brain does the vomiting reflex again...the only sources I could find for this were an article from 1977 and a book on how to set up virtual realities from 2015, so I am not sure I like this one.

I don't know, mostly the cause of this is unknown and I'm not sure that anyone is really out there gunning for the answer to it. We can fix it and people can get over it, so there's probably better things to spend grant money on.

Treatment

Drugs.

Drugs work in the short term, and they are usually anticholinergic or antihistaminergic. The most common ones are scopolamine patches/pills, meclizine, dimenhydrinate, and promethazine. The one you'll probably buy at the store is Dimenhydrinate 50 mg.

If someone is working on a ship or a plane, they'll probably just get used to it. So there isn't any kind of long term treatment.

[justkidneying]

Coloboma and Other Pupil Shapes

I saw a post about a photo similar to the one above, asking if it was photoshop or real. Both that photo and the one above are both real images, and I'll explain to you what is going on with those pupils, as well as some interesting stuff about various pupil shapes we can see in mammals.

Coloboma

This is a condition where the choroidal fissure of the optic stalk does not close completely during development. Basically, your eyes are a protrusion of your brain, and when the optic cup sticks out, it has a slit in it. If it doesn't close, parts of your iris, retina, optic disk, or eyelid. Most of the time, the iris is what is affected and the person has normal visual acuity.

Because the ring of the iris is incomplete (and usually shaped like a keyhole), this person cannot constrict their pupils the normal amount. I have a post about pupillary constriction and dilation here. The person may be overly sensitive to light. There's a surgery to correct the defect, or some people wear colored contact lenses to make up for the missing piece.

You can see coloboma on its own, or with another condition like Patau Syndrome (Trisomy 13), Cat Eye Syndrome (too many copies of chromosome 22), or CHARGE Syndrome (a set of congenital defects).

Now onto the other pupil shapes that aren't round cause I'm an animal science major.

Vertical Pupils

These are seen in small cats, foxes, hyenas, etc. Mostly ambush predators that are active at night and dusk. Vertical pupils are helpful for night vision. The difference in area from the smallest pupil size to the largest pupil size in humans is about 10x as small. In contrast, a cat's pupils vary by about 135x the area. This means that cats can have massive pupils for nighttime, but shrink them down small enough to not be blinded by light during the day.

There's a few theories on how vertical pupils help visual acuity, as they are found mostly in a certain ecological niche, but a lot of these theories are either contradictory or complete dogshit. It seems like a lot of the authors (especially whoever wrote the Wikipedia page) need to take an introductory physics class to learn how light waves work and oscillate. But I will try to explain some things that actually have proof, and I'll link an article (here) that has all the math in it. This is all theory, so I apologize if something is incorrect or doesn't make sense.

So with a vertical pupil, depth is able to be perceived without moving the head through the use of stereopsis. They have a sharper image in the central vertical area of their field of view, and can use the differing blurs of the horizontal to assume depth. Vertical pupils are also more common in shorter animals, which can use the blurriness of the ground to estimate depth, instead of taller animals that might not have as much near ground to use as reference. So, we could say that a taller animal could still have use for vertical pupils, but for night vision, rather than depth perception (however this would not be the case for someone with coloboma, as their smallest pupil size is larger than the average human's smallest pupil size).

Horizontal Pupils

These are seen in horses, sheep, goats, etc. So basically prey animals for the most part. This shape may help these animals see horizontal fields more sharply and decrease glare from the sun.

It is theorized that they allow the animal to have a wider sharp view and still see well enough in front of them to move over rough ground quickly. Since most animals with vertical pupils have eyes on the side of their head, they have smaller blind spots. With horizontal pupils, the sharpness of the image in such a wide field of vision is more uniform that that if the animals had round pupils. This means a horse can see around it and where it is stepping with sharp enough vision to be useful.

Also, these horizontal pupils would be most useful if the pupil stayed level with the ground, meaning the eye would need to rotate as the pitch of the head increased or decreased. This is seen in many of these animals, that their eyes rotate to keep their pupil horizontal.

End Notes

This was a pretty fun post to do, and I hope it seemed like it flowed well to put these things together. I hope you guys know a little bit more about eyes. I love eyes. I could talk about them all day. Maybe I'll talk about some cool neuro/ocular stuff soon.

[justkidneying]

Paradoxical contraction

If you want to dilate or contract your pupil, what do you do? You contract your muscles, of course. It sounds odd, but contracting two different muscles either leads to the enlargement or the reduction of pupil size. I'll explain how and also point out a flaw I've seen in a few fics before.

Look at that iris (the colored part of the eye). See how there are two parts to it? There is a bigger circle with larger folds, then a smaller inner circle with lots of little folds. The bigger ring is the pupillary dilator muscle. Its muscle fibers are radial (like cartoon sun rays), meaning that when it contracts, it pulls the opening of pupil back, making it larger (mydriasis). Its innervated by the sympathetic system (fight or flight). The smaller ring of muscle is the pupillary sphincter, which has fibers arranged in a ring around the pupil. When it contracts it causes the tightening of the circle, and the constriction of the pupil (miosis). It is innervated by the parasympathetic system (rest and digest/feed and breed). It is also activated as part of the accommodation triad, which allows you to focus on objects that are near to you. The top layer of both muscles is covered by epithelium that has melanocytes (melanin producing cells that give animals color).

And for the writers: I've come across the phrase "his pupils constricted in fear" before. The sphincter that contracts when you are afraid (using your sympathetic nervous system) is your asshole, not your pupillary sphincter. When you are afraid, your eyes dilate, which makes sense because you want to be able to see everything.

[justkidneying]

Why you can't actually transplant eyes (yet)

This one didn't win the poll, but someone specifically asked for this topic, so I'll write about it anyways. Also, as someone who is working towards being a trauma surgeon, this is a topic I'm really passionate about.

So, I think a lot of people have a misconception about whether or not it is possible to transplant eyes. We transplant a lot of other stuff, so why not eyes? Well, you can transplant pieces of the eye, like the cornea, the clear part at the front of your eye (which is avascular). You can also replace the lens with an artificial one (the lens is also avascular). This is how you can fix cataracts, just taking out the old shitty lens and putting in a clear new one. That procedure can be done in a clinic in like thirty minutes (which is fuckin crazy if you ask me).

But what we're talking about here is taking out the entire eyeball and replacing it with a donor eye. It sounds cool as hell, so why is it so hard? First off, the eye is a part of the central nervous system (the first two cranial nerves, are in fact part of the CNS, not the PNS). So the optic nerve (CN II) is what carries special sensory information to the dorsal brain (occipital lobe). To control eye movement, you have CN III, IV, and VI (oculomotor, trochlear, and abducens nerves). The oculomotor nerve controls eye movement, pupil constriction, and the upper eyelid. The trochlear nerve controls movement of the eye downwards, outwards, or to the nose. The abducens nerve moves the eye outwards. Several other nerves are involved in keeping the gaze level with movement, visual tracking, and parasympathetic/sympathetic functions (rest and digest vs. fight or flight). The point is, eye nerves are complicated as hell.

The blood flow to parts of the eye is also very complicated, and is very difficult to properly reattach for full perfusion (esp the retina).

Now, onto the good parts. So the eye is what is called "immune privileged." This means it has protections against the immune function of the body (to avoid autoimmune attacks). The eye has no lymphatics, few immune cells, and immune suppressing chemicals. This makes it a great place for implants, as it is unlikely that the body will attack the foreign tissue (stem cell implants are becoming more common).

The first whole eye transplant was done about a year ago (November 2023), and so far the eye is still there with adequate blood flow. However, the guy can't actually see out of it. The surgery took 21 hours and involved a huge team of some of the best surgeons in the world. It was not an easy thing to do. They also implanted some stem cells with the optic tract in hopes to regenerate it, but that still hasn't restored vision in the eye. So, while this case is a major win in the area of eye transplants, there is still a ways to go.

So why do we even need to do so many eye transplants? Well, all kinds of things can lead to the loss of the eye, whether it be disease or trauma. Surgeons try very hard to keep the eyes in a patient, but that isn't always possible. Sometimes the tissue is too destroyed for repair or the damage causes permanent pain. Enucleation is the removal of the eye. Usually, as much of the optic nerve is left as possible, as well as the musculature. Possible options after healing include fake eyes (like glass ones), which can be crazy realistic and can be moved with the eye muscles.

I hope this was an interesting read, and thanks for reading my ramblings. I didn't feel like the typical post format would work for this one, and I like to imagine it like a bonus since it didn't win the poll, lol.

[justkidneying]

Q: Are the eyes and optic nerve (aka CN II) part of the central nervous system or peripheral nervous system?

A: CNS

I know we say that the PNS has 12 cranial nerves, but that is false. It has 11 (CNI,CNIII-CNXII). How do we know this? Embryology, my dude (and pathology)

So the eyes come out of the brain around 3 wks after fertilization. They are a diverticulum of the brain (as everything in your body is a diverticulum of something else). The retina and optic nerve come out of the neural ectoderm. The lens comes from the surface ectoderm. If you know embryology, everything in medicine and anatomy will become so much clearer, trust me.

*we are like balloon dogs, just one long tube that got twisted around a bunch*

Anyways, pathologically, we can tell that the eyes are part of the CNS as well. What does Multiple Sclerosis do? It demyelinates the CNS....and the optic nerve. What does Guillian-Barre do? It demyelinates the PNS...but not the optic nerve.

So why do we call the optic nerves...nerves when they should be a tract? (remember that axons of the CNS are called tracts, and in the PNS they are called nerves) Honestly, I have no idea. It was probably some dumbass anatomist...and he probably also thought humans have one heart...