 7 from 31 years in the VA and NIH research systems. So this is my first 30 years. And it is a couple of ophthalmology gems. We're going to talk about the abnormalities associated with albinism, any form of albinism, any mammal, absolutes that occur at the optic chiasm if you don't have normal retinal pigment in the first trimester of development. Whether you're a mouse or a guinea pig or a ferret or a mink or a white tiger or any of the mammals you have abnormal crossing and crossing at the optic chiasm. Even in the most primitive nervous systems, there's usually both ipsolateral and contralateral projections. This is the part of the nervous system of a fruit fly. They have a lateral-like system with integration of the two sides of the nervous system. So throughout from the earliest creatures, the grisaucula that preceded mammals by a couple of hundred million years, you have an attempt for organization in both sides. Most vertebrates have some retinal fibers that do not cross at the, I mean fish, snakes, amphibians. Most, but there's no absolutes and there's no absolutes even between closely related species, like just different kinds of toads. Some have and some don't. And in fact some, some stay ipsolateral, but then after they get past the chiasmic area, they go back over to the contralateral. So there's just, there's all possibilities. Most fish have some, but the most common genetic model in fish, the zebra fish, don't have any. I just want to express what the variation is. Snakes have more than fish. And in some, we all, we're used to the optic chiasm is that they come back a couple of inches behind the eye and they all interdigitate at the optic chiasm and sort out some cross, some don't cross. Well, in many fish, it's like this. There's no interdigitation. It's just a bunch of fibers from this eye and a bunch of fibers from this eye and they just sort of, they cross like this. They don't interact at all. Weird. And in the lower than mammals, most ipsolateral fibers only project your primitive areas, the hypothalamus, the primitive portions of the dorsal, of the lateral geniculate, not the dorsal lateral geniculate. And to protect them areas that control eye movement and coordination of eye movement with all of the brainstem connections. They don't have them because of lacking neocortex. They don't have the projections onto the cortical surface. The visual system, as we think of it, is only primates, where the phobia, fibers temporal to the phobia don't cross, fibers nasal to the phobia do cross. That's only in primates. In the lower vertebrates, the low mammals, it's sort of random. They come from all over the retina and they just are in the nerve, just like a random variation. There's no segregation of crossed and uncrossed fibers. Just think of, in fact, I'll show you a slide in the next couple of minutes of even a cat chiasm. It's that way. In higher primates or boreal primates in humans, there's a bundle that stays lateral for the ipsilateral fibers that stay on the same side of the brain and a bundle that cross at the optic chiasm. It's just like this, two separate bundles, completely segregated. No interdigitating. Whereas in the lower vertebrates, the snakes, the amphibians, the reptiles and that, they're just, they come from all over the retina evenly and then in the optic nerve, they're just evenly spaced. There's not an organization. Here's our primate visual system. In no animal do they, is there 50-50? Humans and some of the arboreal primates, tritolium primates, they really depend on good stereo vision because you only get to miss a limb once if you're 100 feet above the ground. Do we have close to 50-50? So it's about 45%, 55% that 45% don't cross and 55% do cross. In the rodent and rabbits, the proportion is only 5% or 10% don't cross. If you think of placement of eyes on the head, visualizing animal placement of eyes on the head, you can guesstimate the number of ipsilateral fibers because it increases as temporal retina increases. The fewest I've ever examined are guinea pigs. Think about guinea pig. Their eyes are more on the side of the head than amphibians and snakes and other than some fish. Well, they have one or two percent. That's it. That's all their temporal retina. And then if you think, just think of dogs, horses, they're about 20-25%. Cats are about 30-35% and then you get up into the 40% when you get into primates. I talked about the organization and disorganization within the optic chiasm. In the primate visual system, you have this orderly bundle of uncross fibers like so. Whereas in the rodents, rabbits, and the lower mammals, they're sort of haphazard. They come to the chiasm and then they bounce away from it. And that's how the organization is if you look at the embryo in the embryonic development. If one reviews the literature and they were looking for it, which nobody did until 50 years ago, if you look in the literature, there have been psychological studies since the 20s where they took rats and evaluated could a rat with only ipsilateral pathways, was that enough information to make pattern judgments. And a study by a guy named Carl Lashley in the 20s said, yes. And then three studies in the 30s said, no. And then some other studies in the late 50s said, yes they can, yes they can. And then this was picked up in 1965 that, oh, what's the difference? Those using pigmented models said, yes they can. Those using albino models said, no they can't. It was not a thought to anyone that there could be a visual system organization difference between closely related species, sometimes litter mates. Guy named Charles Sheridan did a split brain study for his thesis that was about 1965, which he compared. He sectioned the brains all except for the optic chiasm between the two hemispheres and compared learning of, learning with one eye and then transferring to the other. And he found that the learning didn't transfer in the albino rats. And he hypothesized based on that behavioral study that, this quote was something like, perhaps the paucity of uncrossed fibers is either even further exaggerated in the albino. That same year within a few months a guy at University College London named Lund, L-U-N-D, who by the way was here for a decade or more later in his career. He published the first paper of gene repair and mouse models were for RP back years and years ago. Lund saw Sheridan's paper. He sliced up the dorsal lateral geniculate chiasms of albino and pigment and rats and said there are no uncrossed, organized uncrossed optic fibers and albinos, but there are in pigment and rats. Unlike primates and even cats, by cats I mean cats and general tigers, not just house cats. Unlike our lateral geniculates, which are strict laminations, have most of you seen, ever seen geniculates, dorsal outer geniculate where you have a layer across and then layer of uncrossed, a layer across. So it looks like, I'll show you one, it looks like this. And down through each layer is a point in the world perfectly organized so that if you're looking straight ahead and there's a little flashing LED right here, it stimulates fibers right down a column right through all those layers. And then that is goes on to the visual cortex and feeds to binocular cells and that's the concept of stereo vision. It's an anatomical wiring that gives you this point in space is maintained through a column in the geniculates and then on to binocular cells at the cortex. If you don't have that, you don't have binocular stereo vision. In the rat geniculate, because there are about 90% crossed and 10% uncrossed, there are not these laminations or layers. There's a great big wad of crossed with a pocket of uncrossed, here's the pocket of uncrossed. So these are different layers, whereas in the albino, whatever uncrossed fibers they have are fragmented up into pieces and there's no pocket on the other side. The animal that was studied the most for the effects of this, the highest animal available in numbers closest to the primate visual system is the Siamese cat. Siamese cat is an albino. It's a special kind of albinism that allows pigment on the cold parts of the body. The picture of Siamese cat, picture where they're pigmented. When they're born, they're as white as a white mouse. And about the time their eyes open, about two weeks later, the peripheral portions start to form pigment, because they've been out of the warm womb for a while. You could take a five-year-old adult Siamese cat, and if you put it in a cage that was real warm, when his new hair grew back in, you could turn him all white again. If you simulated warm temperature, and you get the same homologous gene in Himalayan rabbits, Himalayan rabbits, black ears, feet, tail, Himalayan mice, Himalayan rats, that Himalayan gene is this temperature effect. So it needs coldness to work. But inside of its eye, it's as albino as a white rat. Therefore, its visual system is as albino as a white rat. Here's a picture I took from a Scientific American Review article by a guy named Ray Guillory, who's lab did the most anatomy in the Siamese cat back almost 50 years ago. The reason many have crossed eyes is they don't have normal wiring to their brainstem nuclei, because of the lack of uncrossed optic fibers. And so they have poor eye muscle control, and most have strabismus, either iso or exotropia, mostly iso, because they're miswired. So a lot of the things in albinism research have had applications to learning more about what eye movement, control of eye movement. Albinos also have reverse nystagmus when they look at a rotating drum. It isn't the same as ours. It goes the opposite direction because of their brainstem being miswired at the inferior superior colliculus and pre-tech collider. Okay, this is just two of the laminations. These are from Ray Guillory's 1974 review article on Scientific American. This is just two of the laminations, and this is the point-to-point representation I was talking about the outside world. So if you take points in the outside world in the normally pigmented primate or cap, they line up so that point 13 is the column there, and then this extends through several more layers. And then onto the cortex, those same cells land at the same spot. And if you have this integration from both eyes, that's the underlying anatomical basis of stereovision. The reason that you can tell in the fly test that they chained to jump off the page. The first time I showed the fly test to a human albino, I was standing behind him and I was explaining the fly test, and I just like you went to person. You see how the wings come off the page, and he looked at it for a few seconds, and he turned, and he looked over the shoulder at me like this, and he said, it's a flat picture. Because they also, human albinos don't have the underlying basis for binocular stereovision, so they don't see the fly wings coming off. What do we get in an albino? A Siamese cat? Because there are too many cross fibers and much fewer uncross fibers, it completely destroys the organization of the geniculate nuclei. Those excessive cross fibers have to go somewhere. Whatever they go, they go into the wrong layers. And so when they go into the wrong layers, they screw up the representation of the outside world, so you do not get the same point in the outside world lined up in the geniculate or projected on to the cortex. So you have few, if any, binocular cells at the cortical level. This is the phenomenon throughout mammals. It's just a much more primitive system in the rodent and rabbit than it is in cats and humans. My contribution was I mapped the cortex. This is the mapping I did 50 years ago of Siamese cats. So these are the crossed evoked potentials. There are almost no uncrossed evoked potentials. The cat and all but primate visual systems are not in the occipital pole. They're on top of the head. Why? Because they don't have prefrontal cortex. The reason ours are in a sacral pole is when you have prefrontal cortex, what happens to the visual projectionary on the top of the brain? It has to go somewhere. So with the development of the frontal lobes pushed it back. So in rodents, guinea pigs, rabbits, cats even, it's on top of the head. And then humans it moves back to the occipital pole. One of the points of the study I did with Siamese cats, I compared, my dissertation was mapping the crossed and uncross optic systems of rats, guinea pigs, cats, and rhesus monkeys, and recording scalp evoked potentials from humans. Comparing all five species and crossed and uncross. The previous picture shows, you've got this big difference. The question is, can you tell it at the scalp level? So before I took the skull off and did the mapping, I did a single electrode comparing pigment and cats to Siamese cats. And yes, you could tell the difference. Even a gross level from just one spot in the middle of the visual cortex. So this is the underlying basis of being able to detect this in humans using scalp evoked potentials. Okay. Before you guys were born, a decade or more before any of you were born, it was unacceptable for humans to be considered like the rest of animals. We're just different. Our gene, everything about us is different. We're not like animals. When I submitted the first human paper in 1973 showing four genetic kinds of albinos, the paper was rejected by all reviewers. And one said, close to a quote, I applaud Dr. Creel for his youthful enthusiasm. But what he needs to do is read Dwayne's anatomy of the visual system. That was the response. Humans were not like Siamese cats. Humans are different. Fortunately, the editor overrode all the reviewers and published it anyway. But that was the attitude just over 40 years ago. And now they're putting human genes in mouth models. This is a litter of albino cats, not Siamese, on my ex-wife's lap back about 1980. A woman named Sally Springer had a barn cat outside of Sheridan, Wyoming that would have a litter every six months of unknown parentage. And it wouldn't allow a person within 50 feet of it and would produce these litter of cats. And after having these for several years, the cat had a litter that had three albinos in it. And the cat brought them one at a time by the nap of the neck to the porch. The cat that wouldn't let people within 50 feet of it, it went to the barn, brought one albino, went to the barn, brought another albino, brought to the barn and got another albino and sent them. And she knew enough about cats to know that foremost geneticist in the world for cat genetics was a guy named Roy Robinson in London, which is another half-hour story. He was like Charles Darwin. I visited him in his house. His house was whole. The doors were just my size. The place was built in like 1450 or something like that. Roy Robinson made his living running a plant nursery. No academic affiliation. He wrote the book on the genetics of the Norway rat that's aside the web search dictionary. And he wrote the books on the genetics of cats. And she wrote Roy Robinson and said, I have albino cats. Are you interested? And he wrote back to her and said, I met him later after this, that no but called on Creel. One day my phone rang and I was told this story. And we went to Sheridan, Wyoming, and at first just got one and then went back another time when she called because she had a litter. And this is, we brought this litter back and so for about 20 years I had a colony of true albino cats that I, I crossed them with normals and then back crossed to keep them genetically strong. And one of them, that's, he ended up on the cover of science. I believe it's this guy. But I don't remember for sure. This guy when he grew up, his name was Willie. And I loved it because after this was published, after this was published I got these hate letters that were forwarded me from science because where is that cat now? Did you torture that cat? Is that cat cut up and on slides now? And Willie was sent to Toledo, Ohio to be the breed stud for a colony. And so I said, Willie's living in Ohio. And I took this photo, I had him on a stool with a black, with a red black cloth background set up in those days with a slide camera. And you had a, had a bulb thing where I could take a picture and I would rattle keys and take pictures, took pictures. I took 240 shots. The other 239 looked like this. And then one was, this was of the one. This is a fondness of one of the albino cats. Okay, this is the optic chiasm of one of Willie's close relatives. The lighted area are the crossed fibers. This sort of equals smattering that I talked about are the uncrossed fibers. The really primitive projections up into the super chiasmic nuclei towards the hypothalamus are unaffected. That's what those, that's what those are. They're really phylogenetically old projections. Just the quote new projections. Those projections are found back into chordates, earliest vertebrates in that the projection to coordinate with mostly it has to do with information for migration. To send visual information up into the hypothalamic nuclei that control the pituitary and the changing of hormones with the seasons. A question. I took the first year of medical school except they wouldn't let us in gross. But I took the rest of the first year of medical school as my minor. And one of the questions on the, on the neuroanatomy exam was describe all of the pathways that would cause a woman living in far north lab land to not have her menstrual cycle normal. What they wanted was all of the layers of the retina to the chiasm to the projections into the hypothalamic nuclei affecting the control of hormones. I think I was the only one that could have gotten that one right. So this shows the geniculate. I talked about the layers. These are the layers of a normal cat up on the upper right. This is an albino cat on the left. These are the uncross fibers in the albino cat. Here is the little tiny pocket of uncrossed in the cross geniculate. All of the rest of those layers of the geniculate unlike the normal cat are crossed and this little tiny pocket is this little tiny pocket right there. So the probably 99% crossed in the albino cat. An interesting thing is as you ascend up through the visual system by the time you get to the cortex there seems to be a lot of auto correction as far as perception and everything. So you get 99% crossed with 40% of the lateral geniculate cells abnormal but when you get up to primary visual cortex C17 and 18 it's much less in number. So there's eye movement disorders I mentioned. Most albinos almost all have nystagmus but there are no absolutes. No absolutes at all. I've seen albinos. I saw a fellow here within the last couple of years that was 40 before he found out he was an albino. He had 20-25 vision. No observable nystagmus but he had his OCT showed a fovea as flat as a mouse. Greatly affected are the brainstem nuclei and it's so complicated there's about two people in the world that don't understand it. One of them is a guy I collaborated with back in the 70s. His name was Roland Gioli. He's retired now. He's a year or two older than me. He was at UC Irvine for years. He published the first paper after Lund showing the abnormality in rabbits back in the 60s. Rolando Gioli actually although he used Roland here but he's gone back to Rolando because he was born in Italy. This is a whole other topic if you get really interested in the different theories of the causes of dissociated vertical deviation and latent nystagmus which are quite different in albinos. These are some of the features of albinism. You have foveal hypoplasia and almost all. In fact it's just about an absolute. Vascular intrusion into the foveal avascular area. So they don't have the sparing, they don't have the reading around the fovea like pigmented people do. You have the reduced visual acuity and contrast sensitivity generally but there are some as good as 20, 25 to 20, 30 vision with no foveas. High refractive errors and nystagmus and high incidence of strabismus, translucency, reduced number of total of ganglion cells not just reduced number of uncross, reduced number of photoreceptors, misrouted optic projections. The most common feature among all forms of albinism in humans are the misrouted optic projections. So the albino is a model for all of these various conditions and albinism occurs in all organisms from fruit flies to humans. This is a really big allocator. There's a private zoo outside of Phoenix. It's quite interesting that it's got you know as many animals almost as say the Hogle Zoo does and this great big thing is like almost as long as these two tables. Really big. I took that myself. You see albinism in everything. Plants not just limited also to animals that we think of animals but also plants. Melanin is I think of it as I can't think of an older system in the last billion years and melanin than melanin pigment. Not just in the visual system but in general in pigmentation. Okay there are different types of occultaneous and ocular albinism. You only need the ocular to be affected. There's a couple. This is their wedding photo. There's a support organization called NOAA. The acronym NOAA which stands for National Organization for Albinism and Hypopigmentation. They have a quarterly magazine and this is one of the covers of their magazine. These two be interested if this is just occurred a year or two ago and I have no idea if they've had any children. It would be interesting if they're the same gene. If they're not as pigmented as us. Because there's a lot of different genes and a lot of different loci. But they met through this organization as teenagers and lived in different parts of the country. And then they just had a long distance quote relationship and then they got married in the middle of college a couple of years ago. Talking about the different genes. These are just characteristic of two of the main types of genes in African Americans. The time they have no pigment at all used to be called tyrosinase negative albinism. Now it's called type 1 and type 2 used to be called tyrosinase positive that could form some kinds of pigment. If these two different types marry type 1 and type 2. They're not only on different loci. They're on different chromosomes. Type 1 is on 11. Type 2 is on 15. There's no interaction at all. They miss completely. All of their children are normally pigmented. This particular family. I didn't know them. It occurred before I got into it in the 50s as photos from the 50s. The doctors took the father aside and were telling me they were sorry to have to tell him that he wasn't the father. And the father and the this man said to them says well it's obvious to me that she's one kind of albino and I'm another kind of albino. So he was he was half a decade ahead of the positions that were counseling. Now we know there are hundreds of loci. So type 1 alone over 100 mutations and that number is old. It's on 11, Q, 14 to 21. This is a guy you've seen him before. Do you remember? Dale. This is Dale. Dale's, I don't know if I'll get to it at the end or not. Dale's auditory brain stem responses which are also abnormal in albinos. They have differences in their auditory pathways also, ipsilateral issues. His auditories were published in Science. So this is the concept of humans and higher primates. This is us. At the fovea, the fibers temporal to the fovea are uncrossed, the fibers nasal to the fovea cross in a very organized fashion. In albinos up to approximately 15% into temporal retina also cross. The percentage varies hugely in humans and we don't know exactly because the closest we've gotten was functional MRIs. The guess is anywhere from like 70 to 90%, depending on individuals and their type of genetics. We know that the more pigment, the less the less are abnormal. So you get more uncrossed, the more pigmented, whether it's an animal model or in humans. This is our fovea. We're all familiar with our fovea. The reason I display it in color so you can clearly see the nerve fiber layer, how it stops a millimeter or so before the foveal pit. Again, normal fovea. This is fovea of a human albino. It's essentially the same as a rat. Here's again a normal fovea. Here is an OCT of an albino fovea of a patient seen here. The nerve fiber layer runs often right across the whole fovea. This is a mouse. This is a human. This is a mouse. This is a human. Here's a comparison of directly normal fovea albino fovea. These are four different individuals from here, seen here or through the years, in their fovea area. This is from an article by McAllister, who's at Minnesota, showing different individuals and different degrees of variation in foveas with the normal of the bottom two. Again, showing variation of four different genetic types, one, two, three, and four. So you normally have the central sparing of the vasculature around the fovea. This is an albino. The microcapillaries can run right directly through where the foveal area is with no sparing at all of the area for vasculature. Again, here's a direct comparison. Normal albino B. Normal albinos, three albinos. So here's again the primate visual system. If you record a little more lateral than 0102, they're called H3 and H4. And you record across the occipital pole while a person views a pattern stimulus in albinos because of nystagmus. You need to use pattern onset because pattern reversal just exacerbates their nystagmus. Dorsal lateral geniculate. Again, the reminder of the difference in the projection. So if you record across occipital scalp in one of us and change right eye, left eye, you will get usually a polarity that is not completely flat. But whatever it is, it will be quite similar whether you stimulate the right or the left eye. Because albinos, using a pattern onset, offset like this, because up to 90% or more cross, when you stimulate the right eye, all the potential goes to one side. And when you stimulate the other eye, all the potential goes to the other side. So the consequence is the polarity completely flips 180 degrees. Interpreting these is not advanced calculus. So throughout the first couple of hundred milliseconds, the signals reverse, reverse, reverse, reverse. This is Dale again. This is Dale showing multifocal evoked potentials crossed and uncrossed The big blue one is the cross system. The smaller red ones are the uncrossed system. And you can see that up to at least 15 degrees lateral, up to at least this far, you get reversal. It takes an albino with really pretty good acuity. Dale, he lost his driver's license in California because they had an accident and they blamed it on being an albino. But he could he could pass. He was 2040. He could pass and he had driver's license in Utah and rode a motorcycle and in California too. And then he had an accident and they took it away from him. Because you know, he looked you know, he has, he had strabismus and his eyes were going like this. So it's hard, he couldn't convince him that he was really as good as most people. So here is an albino with 2030 vision. And there's the OCT. Amazing. I was amazing. In the literature though there is a paper by a retina specialist at Stanford named Michael Marmer, M-A-R-M-O-R, Michael Marmer and he found a bunch of normally pigmented people like us that have these kind of phobias. And we're 2025 and 2030. It's just amazing. So we talked about type 1, type 2. I said it's on 15. It's a different metabolic cause. You also get some association maybe from linkage with Prader-Willi syndrome and Angelman syndrome and perhaps some Asperger syndrome that are on 15 in adjacent nuclei. If you select for Prader-Willi syndrome individuals that have a history of all their life being very lightly pigmented and often their parents said that as infants they had nystagmus. If you select for that group, the majority will show misrouding. It's probably a linkage. Patient coming up, no stereopsis, 2030, no nystagmus. This is their fundus. There's their phobia. There's her evoked potentials. In spite of 2030 acuity and no nystagmus. Through the years I've tested several that live completely normal lives because they were similar to her. They just thought they, you know, because they were panpanelism Scandinavia or something. They passed driver's license tests, never had a particular issue because they were 2030, 2040 vision. Type 3, as we go down they get rarer and rarer. This one's on chromosome 9, B323. These were first tests. I was on in Nigeria in about 1976, a long time ago. At the time we thought it was just something peculiar within the African population, but it's turned out to be universal worldwide. It's just really rare. In this African population they had this unusual reddish color, so we called we, I didn't name them. I was on an anti-study team and I examined 122 albinos from 88 families in Central Nigeria, Africa, among the EBO. And the other three were interested in the genetics and cancer and stuff like that. It's just, it's like a lalbinism, it's like a lethal disease in there because they will work as cane cutters and stuff with no shirts on. And so they die of skin cancer in 1922 and stuff like that. So the ones we saw, this is close to a correct color. They were this reddish color. But as I said, now we know it's worldwide, it's no longer called Rufus. It's called OCA3 and it's on chromosome 9. Type 4, different cause, different gene on chromosome 5 in humans. And the variation is tremendous. This is a Dutch kid. In 1980 I went to the Netherlands version of the National Eye Institute for most of the year to study albinos. Why? Well, try to think of trying to come up with a bunch of albinos here. They all go to different doctors. It would take you forever to come up with them. I went to Amsterdam after about a weekend I met with their geneticists and they said, would 100 be enough? Because being socialized medicine, they were on the computer. They know where they were and being a Germanic society they would just call them and say, be there. The doctor wants to see you next Monday at 9 o'clock. Be there and they come. Type 5 we're getting rare and rare as extended interbred Pakistani family. Type 6 extended Chinese family different loci on 15 than the ones normally seen among Europeans. Type 7 limited to the Pharaoh islands. Different chromosome 10. All of them have this reversal. How are we doing on time? 51? Well, let me get through here. So misrouted optic projections is the most reliable and measurable concomitant when you go across all forms. Let's see what I've got here. Talked about that. Many genetic factors. So, many studies were done in animal models back in the 70s that determined that different levels of ocular pigment were correlated with different levels of goodness of the visual system. These are some of them that I studied and that we looked at the dorsal and lateral geniculate nuclei of them. This is real. That's not a contact lens. This really exists. Those are my hands. It's another kind. I don't know if you can tell but the eyes sort of reddish. So, we only have to be ocular albinos. So, all of those X-linked ocular albinos, they all have the misrooting just like the full albinos. And I don't know if I have it. This is a fellow. This research was done before Randy Olson came here in 79. At that time I was at the VA as a career researcher and for humans I collaborated with Wilmer in Minnesota. So, I went to Wilmer in the neurology department. Let me use their computers. And I did the evoked potentials on ocular albinos. This is this guy I just showed you. Red reflex fundus This was a woman in the Netherlands. It was a carrier. She brought her sons in. These are the two sons and their fundus. You saw how different they were. One had been known that he was X-linked ocular albinos since birth in spite of being so dark. But since his brother was there we tested the brother too and the brother was also. But his expression was he just looked like us. He had no symptoms at all unless you looked in his eyes. Again how dark these guys are fundus fundus So back to the Wilmer study ended up with another science cover that showed that human ocular albinos only needed to be in ocular albinos. And this was his fundus photo. So any of the disorders that have lightness and the symptoms of albinism along with them like selected both selected in a Hermansky pudelock which is found on all of these chromosomes and there's going to be more because they found 17 in mice. So these are the ones published in human Hermansky pudelock syndrome. To remind you they have the bleeding diathesis and a whole bunch of other problems Hermansky pudelock syndrome. This is Chidiak this is I believe is this the Chidiakagashi Chidiakagashi syndrome baby. They have the bleeding disorder susceptibility to any fever producing infections so they look like battered children because if they bump into anything they brew so easily. This is a Chidiakagashi syndrome child. To get these I went to Indiana they had a couple there and went to NIH to Anthony Fauci the famous HIV guy. He had a pair of brothers at NIH that I went there and tested. These are literate Chidiakagashi syndrome cats showing the hypopigmentation and because they were cats we got to slice up their geniculates and their geniculates are fragmented similar to that of the Siamese cat. Instead of having the even layers like B would be the even layers and then the fragmentation you see is in the Hermansky pudelock. So that's just your Prader-Willi syndrome I told you that. These select for the hypopigmented including redness red hair Angelman syndrome they're all on 15 and probably because of linkage that you occasionally see the albinism Aspergers they're really interesting at least a couple that I've seen the boy I'm thinking of let's see here's the VPs of a boy. He had no ocular symptoms at all he was a real hyper his mother had to tell him to shut up so that we could test him and he had the vocabulary of like an Oxford English major and he was like 12 years old they'll have the real high functioning and often really good vocabularies that was his fundus in spite of being no visual complaints and no observable nystagmus. VG syndrome very rare never seen in the United States but they have all sorts of issues and the oldest one to ever live lived to be about 7 and the one we examined lived to be about 4 Kale they're a-closal in addition to be a partial form of albinism this is the one we tested examined this is the fundus it was really tough to get an OCT to do it with a hand held and so the quality is not very good they can't walk this is the visual potentials showing the reversal in this particular one so these are the possible theories and I think they're all wrong I think it's atavism do you know atavism is things like a person being born with a tail it's the it's the expression of a long lost feature what I think is the absence of melon and pigment in the retina because melon is not there and it's so necessary for the formation of the retina if it's not there in the retinal pigment epithelium the genetic programming reverts back to the previous step in the development of the species that humans fall back to cats cats fall back to mice mice fall back to amphibians and fish I think it's atavism I think it's triggered by the lack of melon and pigment that's it sports fans but also they have the auditory issues too they have the issue of like stereo vision they have poor auditory localization also and they found that they have fewer binaural cells in the brainstem than normally pigmented rabbits and cats and it's all one big picture