Eyes on the Mind: Retinal Clues to Schizophrenias Genetic Roots

A groundbreaking study has found that our eyes may hold subtle signs of schizophrenia before symptoms ever appear. Researchers from the University of Zurich and ETH Zurich discovered that people with higher genetic risk for schizophrenia show slight thinning in specific layers of the retina, even without a diagnosis. 

Using data from nearly 35,000 participants in the UK Biobank, the study linked schizophrenia-related genes to reduced thickness in the macula, the retina’s central region vital for sharp vision. A key discovery was thinning in the ganglion cell-inner plexiform layer (GCIPL), particularly among individuals with genes tied to inflammation. The likely culprit? Neuroinflammation. Higher genetic risk was also linked to increased levels of C-reactive protein (CRP), a marker of inflammation, which may help explain the retinal changes. While retinal imaging isn’t a stand-alone diagnostic tool, it could become a useful, noninvasive way to monitor risk when combined with other markers. The research adds weight to the idea that inflammation and neurodegeneration play a role in schizophrenia, and that the retina might offer a glimpse into the brain’s hidden battles.

Sources:

https://www.insideprecisionmedicine.com/topics/precision-medicine/retina-thickness-offers-noninvasive-insights-into-schizophrenia-genetics/

https://www.nature.com/articles/s44220-025-00414-6#Sec2

Eye Color And Genetics

Eye color is determined by the pigmentation of the iris, with variations ranging from light blue to dark brown. Genes associated with melanin production, transport, and storage influence eye color. The OCA2 and HERC2 genes on chromosome 15 play pivotal roles. The OCA2 gene produces the P protein that affects melanin levels in the iris, while the HERC2 gene controls the expression of OCA2. Other genes like ASIP, IRF4, and TYR also contribute to eye color variation. The inheritance of eye color is more complex than previously believed, as multiple genes are involved. Disorders such as ocular albinism, oculocutaneous albinism, and heterochromia affect eye color due to genetic mutations or developmental issues.

A gene-based therapy partially restored a blind man's vision

 A 58 year old man with retinitis pigmentosa can now see and count objects due to a new gene-based therapy that "rewires" nerve cells in the eyes known as optogenetic therapy. Vision is still limited but more light is able to be picked up by the eyes and special goggles are required to assist. The therapy uses a light-sensitive protein to make nerve cells react and signal the brain when hit by a certain wavelength of light. Different from gene editing and traditional gene therapy, which can only assist in the degradation of eyesight and can only target certain genes, optogenetic therapy can aid with someone who has completely lost their vision regardless of what gene or disease caused the blindness. A virus was used to deliver instructions to the eye cells to create the light-sensing protein. As this is not a cure for blindness, it is a step towards the progress of neutralizing blindness.

Gene therapy for Dominant Optic Atrophy

 Dominant optic atrophy is a genetic optic nerve disorder. The gene that is responsible for this disorder is the OPA1 gene. Patients who have this gene in an inherited genetic mutated form, have mutated mitochondria's in their optic cells resulting in this atrophy. A therapy has been developed by scientists at Trinity College Dublin. This gene therapy consists of injecting genes to help boost the production of these mitochondrion cells resulting in dissipating symptoms. So far this study has only been tested in lab mice, but is proving to be promising. This would be quite a breakthrough for the Optic focused side of the medical field. (Scientists develop new gene therapy for eye disease)

Source: “Scientists Develop New Gene Therapy for Eye Disease.” ScienceDaily, ScienceDaily, 26 Nov. 2020, www.sciencedaily.com/releases/2020/11/201126085921.htm. 

Links used: 

https://www.sciencedaily.com/releases/2020/11/201126085921.htm

https://www.frontiersin.org/articles/10.3389/fnins.2020.571479/full

Giant Squid, Giant Eyes, but Rather Small Brain Lobes

Many researchers have questioned the deep sea squid's large eye size compared to other creatures who have a much smaller eye size, such as the cephalopods. Research has shown that even though squids have the largest eye orbit in the animal kingdom, they also have a very small optic lobe. This explains that squids do not rely on visual cues for communication like the cephalopods do because the optic lobe, which integrates visual information with motor tasks, is reduced. This new research is of current fascination because it goes against common anatomical sense and raises the question for future on whether there is some other underlying biological reason for this difference in sea animals.

Article

Blue-eyed humans have a single, common ancestor

A genetic mutation affecting the OCA2 gene in our chromosomes resulted in the creation of a switch, which turned off the ability to produce brown eyes. The OCA2 gene codes for the so-called P protein, which is involved in the production of melanin, the pigment that gives color to our hair, eyes and skin. Variation in the color of the eyes from brown to green can all be explained by the amount of melanin in the iris, but blue-eyed individuals only have a small degree of variation in the amount of melanin in their eyes. From this we can conclude that all blue-eyed individuals are linked to the same ancestor, says Professor Eiberg. 
I think mutation of brown eyes to blue represents neither a positive nor a negative mutation. It is one of several mutations such as hair color, freckles and beauty spots. I think this simply shows that nature is constantly mixing the human genome, and creating all sorts of possibilities. 

https://www.sciencedaily.com/releases/2008/01/080130170343.htm
http://news.ku.dk/all_news/2008/blue-eyes/

Why is the Sky Blue?

Have you even questioned why the sky is blue? The logical answer may not be the correct one. Researchers at the laboratory of Markus Meister, Anne P. and Benjamin F. Biaggini, have conducted research on photo-receptors in both rats and humans. Humans have two different types of photo receptors cones and rods. Rods are dim light receptors that can only provide contrast betwwen black and white. Cones are made up fo three different pigment receptors red, green and blue. Mice on the other hand have on two types of receptors medium wavelength (green) receptors and UV receptors. The then discovered that a certain neuron (JAMB retinal ganglion cell) can signal color to the brain because they fire medium wavelength neurological signals and stop sending UV signals. This is the first time this relationship has been documented. the relationship is as follows rods excite neurons which then innhibit UV light detection.
Next researchers decided to see how the vision effects a rats surrounding. They found that two things stood out in rats vision: seeds and urine. These are both the most important things to a mouse or rats since it is a food source nd teritory. Reserachers also believe that the human body follws a similar pathway of rods to neurons which truns off both red and green receptors leaving the baseline blue color which is why we percieve the sky as blue according to Markus Meister, Anne P. and Benjamin F. Biaggini

https://www.sciencedaily.com/releases/2016/04/160414145217.htm

http://www.nature.com/nature/journal/v532/n7598/full/nature17158.html

'Miracle' Gene Therapy To Cure Blindness

Dr. Jean Bennett, a gene therapist at the University of Pennsylvania, and her colleagues, began treating people who are blind with injections of a harmless virus that inserts good copies of genes that are defective in the patient. The genes were inserted into the cells of the retina. The retina is a light sensitive tissue at the back of the inner eyeball. Its job is to receive light and convert that light into neural signals to which the brain uses for visual recognition.

In 2007, researchers began conducting gene therapy clinical trials on ten patients with Leber’s congenital amaurosis Type 2. Leber’s congenital amaurosis Type 2 causes a degeneration of retinas thus limiting vision at birth and progressive blindness by mid life. The ten patients, ages ranging from 20-45, underwent gene therapy only in one of their eyes, the one which had the worst vision. After gene therapy for two or three years, researchers used an MRI to scan deep into the patients’ brains. The MRI showed the visual pathways in each patient was nearly as strong and healthy as a normal persons vision at that age. The MRI scan also showed the untreated eyes had much weaker visual pathways. This observation suggested that regaining sight also helped to rebuild the visual pathways in the brain. This revision is called brain plasticity.

The data collected from this study hinted that the patients’ visual pathways were in better condition after more and more time had elapsed since undergoing gene therapy. Because the pathways improve as more signals get sent through, Bennett and her colleagues are working on larger phase trials to determine whether their gene therapy can be used more widely as treatment.

This article and the research behind it were truly remarkable. The patients undergoing gene therapy are in their 20’s, and one patient was 45. This age range demonstrated visual pathways and brain plasticity could be improved at any age, not just young children. I found this article to be extremely uplifting and encouraging in the field of gene therapy. The ability to use gene therapy in repairing a person’s sight that had been nearly blind is just so moving.

Inheritance of Eye Color

 More than one gene codes for eye color. It is uncommon, but it is now known that parents with blue eyes can have a child with brown eyes. Two separate genes OCA2 and HERC2 can lead to the inheritance of blue eyes. You need both genes to get a pigmented (brown) eye. Both of the genes work together, so it is possible to be a carrier of a dominant trait for brown eyes. So if both parents have blue eyes, but they are carriers for brown eyes, then the child can have brown eyes. Both genes are needed to work in order to have blue eyes (epistasis). Brown eyes are pigmented and blue eyes are not. OCA2 is one of the key genes in determining how much pigment is made, so this gene clearly plays an important role in blue eye color. A lot of pigment gives brown eyes, some gives green eyes, and none gives blue eyes. The HERC2 gene determines if the OCA2 is turned on. So both of these genes play key roles.
It is very interesting that more than one gene codes for eye color. It makes it even more interesting that hazel eyes are possible. The more of inheritance for eye color or more advanced that people used to think.

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Tracking down cause of eye mobility disorder

Could you imagine having a permanent downward gaze and having to tilt your head up in order to see directly in front of you? A condition known as eye mobility disorder causes a person to not be able to lift up their eyes or eyelids in order to see straight. Scientists at the University of Iowa have been performing experiments on mice that would mimic what would happen in humans, in order to help eliminate this disease. About ten years ago, Elizabeth Engle, one of the authors of this paper, identified the mutated genes that cause eye mobility disorder, and she then developed a mouse with the same genes. However, it was still unknown why this type of disorder occurred. Other researchers started to look into this disease and found a swelling in one of the nerves that goes to the eye muscles, which only occurred in mutant mice. Therefore, with further experiments involving normal and mutated mice, the scientists were able to identify the mutated protein and its function.

                I found this article to be very interesting, because it is the start to finding a cure for this disease. As the article states, future research on this topic will hopefully help families with a genetic predisposition for this disease to be able to have normal children without the mutation.

Article: http://www.sciencedaily.com/releases/2014/04/140416162636.htm

Related Article: http://www.ncbi.nlm.nih.gov/pubmed/8771514

Bad Eyes? Gene Found to Affects Retinal Degeneration

Have you ever wondered why eyesight, mainly retina, worsens as you grow? Scientists, from Georgetown University of Medicine, have found that the hormone Klotho can lead to macular degeneration. Scientists have found that the hormone Klotho could increase synthesis of light absorbing pigments, increase of gene expression that protect against oxidative stress, inhibition of vascular endothelial growth, and is found to regulate phagocytosis in the photoreceptors. 

This correlation enables scientist to be able to manipulate this hormone to reduce macular degeneration.
Also, I think this can come handy to even just understand the relationships between hormones and their effects on cells.


http://www.medicalnewstoday.com/releases/267179.php

http://www.uniprot.org/uniprot/Q9UEF7