 All right, good morning, everyone. Thank you for giving me the opportunity to speak to you today. Last week, it was brought up that patients have always and will always ask if they can regrow their optic nerve. And we all kind of chuckled about it. As a result of that discussion and a result of my literature review that I did recently, I thought it would be timely to talk about whether or not neural regeneration is simply some crazy idea from movies like Minority Report or from movies about aliens, or if it's not really that far from reach. Featured on this slide is our star of the today, the Mueller Cell. But before I get to that, I want to talk about two patients. Yeah, two patients now. So MB, it's a 68-year-old male with reports of gradual vision loss of central vision. Exam-finding showed bilateral macular drusen, pigment and outer retina, and RPE atrophy and disruption. He is diagnosed with dry AMD. NR is a 60-year-old female who presents with sudden unilateral loss of vision. This person has a history of amauricis fujax, cardiovascular risk factors. And on exam, there's a pacification of the retina, a cherry red macula, and this person is diagnosed with central retina artery occlusion. So what do these patients have in common, aside from an over simplified case? Irreversible retinal damage, at least so we think it's irreversible. So I'm going to talk about some examples of neuronal regeneration that we have already discovered. So we've known for a long time that the peripheral nervous system has the ability to regenerate. During an injury, Schwann cells, the glial cells of the peripheral nervous system de-differentiate, proliferate, and change function. They go from being a cell that supports conduction and making myelin to a cell that supports regrowth and secretes chemotactic and growth factors. Once the axon is healed, the Schwann cell re-differentiates and becomes a Schwann cell again. Regeneration in the central nervous system is a little bit less robust. However, recent discoveries have shown that there are two areas of regeneration. The subventricular zone and the subgranular layer. The subventricular zone is located, you can see on this section it's a sagittal section, just inferior to the lateral ventricle. And the neurons go to the olfactory bulb and regenerate there. The other area is in the dentate gyrus, and the neurons there only move from one layer to another. Now it's still up for debate why these areas do regenerate, but it is thought that the olfactory bulb is sort of this vestigial function that was there for survival, for need of food, and being able to find a meat. I don't know if that's me. The subgranular layer, it's thought to be more of a current function in that it's part of memory function. The dentate gyrus is part of the hippocampus, which is part of memory formation. So it's thought that this is necessary to consolidate memories. So what about the retina? There's two cell populations that may serve as progenitor cells in the retina. There's the ciliary marginal zone cells, which are only found in adult fish, so we won't discuss that further. And there's a subset of Mueller glial cells. So here we have two pictures of glial cells. The above picture is the Mueller cells under normal conditions. You can see that they traverse the whole retina and their nucleus are in the INL. Under these conditions, it is responsible for homeostasis and nourishment. This lower photograph, which the Mueller cells are highlighted in green, showed that this is a rat retina under stress. So you can see that the Mueller cells are proliferating. They have an increase of GFAP. And you can see some scarring on the upper layer, on the photoreceptor layer. So normally, this Mueller cell reaction is actually not helpful for regenesis. It causes scarring, and it does not allow axons to reconnect. However, there's a subset of cells that have been found that act differently than this, that are actually Mueller cells. They were first found in fish. You can see that there are radial clusters of slow cycling cells. So these were labeled with PCNA, which is a protein that's only found when there's mitosis going on. And they were able to find these clusters of cell throughout the retina. And they were followed over time and found that they actually moved the ONL layer and then became photoreceptors. The chick retina was able to find these cells by injuring the retina. And they were able to produce. So this upper photo shows that the green areas are areas that are undergoing replication. And the red areas are areas that are producing neurofilaments, suggesting that these Mueller cells are replicating and changing into neurons. In the lower picture, bird U means again that they're replicating. And the CHX10 is a transcription factor that's only found in stem cells. So again, it looks like these Mueller cells are becoming stem cells. The only problem with the chick retina is that the regeneration is more limited. There's more bipolar cells, amicron cells, ganglion cells, and not as many photoreceptors. In mammals, it seems to be the same as far as needing injury to make these Mueller cells gain this pluripotency. A study was done, and it showed that upon injury, there's about 0.2% of the Mueller cells that kind of gained this pluripotency. However, a really neat study was done recently where these subset of cells were taken from the adult retina that were showing this pluripotency and put into rat pup retinas. And with time, you can see in this picture right here that they were incorporated into all the different cell layers of the retina, suggesting that indeed they are able to proliferate and make different layers of the retina. And again, there's even more limitations on photoreceptors compared to the fish. So what does this even matter if it doesn't improve sight? What we found is that, sorry, what another study found was that rats with retinal degeneration stimulated with wit and notch have increased Mueller cell activation and increased head and eye tracking due to stimulus compared to controls that were not given wit and notch signaling. And therefore, the increased Mueller cell activation did not occur. So in summary, neuronal regeneration may not be so far off as science fiction. There are examples of neuronal regeneration in the PNS, the CNS, and in the retina. And though we might not be able to regrow an entire optic nerve, the hope is that the current and future work will find a way to activate these Mueller cells in a way that will benefit patients, similar to the ones we discussed above, as well as many other examples where there's retinal damage, diabetic retinopathy, et cetera. Here are my references. And a little about me, I just got back from a fellowship funded by the Door Stoop Charitable Foundation. I was in Ghana for eight months and studied pediatric HIV. And these kids don't have HIV, but they were cute kids in a little town that I went through. The upper picture is Kentay cloth that is a traditional cloth that is made there. The lower picture on the right is a mosque in Larabanga. It was built in 1421 as the oldest mosque in Ghana. And just a little bit about Ghana. It was the first African colony to gain independence. That was in 1957. It's been a peaceful democracy since 1991. And Ghana has an interesting relationship with slavery. About 1 eighth of all the slaves passed through the Golden Coast, which is what the area of Ghana used to be called. And if you can see here, so from Cape Coast, which was the biggest slave castle, there's another slave castle right next to it, Almena and Accra. That's the main area where 1 eighth of the transatlantic slave trade went through. Accra was where I was right here. And then above it is Kumasi, which is where the University of Utah is really involved, as probably many of you know, in both ophthalmology and many other fields. You can see this accident and emergency department is where I actually went and met my dad. He's an ER doc here. And I went and spent some time in the ER with him. That's the new eye hospital in the middle of Konfanoche. And that's the Cape Coast slave castle. Thank you to Dr. Ombari and Judd Kahuna, MDPHC candidate in Ombari's lab who helped me prepare this. And thank you for all the physicians who let me shadow you. I was trying to decide if ophthalmology was the right thing. And thank you for convincing me that it was and is. And thank you to Victoria Smith. She's a PhD at the University of Ghana. Help me get the right stats on slavery. And thank you for all of you listening. Any questions? All right, thank you.