Retinal cells grown from stem cells can reach out and connect with neighbors, according to a new study, completing a “handshake” that may show the cells are ready for trials in humans with degenerative eye disorders. Over a decade ago, researchers from the University of Wisconsin–Madison (UW-Madison) developed a way to grow organized clusters of cells, called organoids, that resemble the retina, the light-sensitive tissue at the back of the eye. They coaxed human skin cells reprogrammed to act as stem cells to develop into layers of several types of retinal cells that sense light and ultimately transmit what we see to the brain.

During 2022, Gamm and UW–Madison collaborators published studies showing that dish-grown retinal cells called photoreceptors respond like those in a healthy retina to different wavelengths and intensities of light, and that once they are separated from adjacent cells in their organoid, they can reach out toward new neighbors with characteristic biological cords called axons.

“The last piece of the puzzle was to see if these cords had the ability to plug into, or shake hands with, other retinal cell types in order to communicate,” says Gamm, whose new results on successful connections between the cells will be published this week in the Proceedings of the National Academy of Sciences. Cells in the retina and brain communicate across synapses, tiny gaps at the tips of their cords. To confirm that their lab-grown retinal cells have the capacity to replace diseased cells and carry sensory information like healthy ones, the researchers needed to show that they could make synapses.

Source: https://news.wisc.edu/ 
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https://www.thebrighterside.news/

Retinal cells grown from stem cells can reach out and connect with neighbors, according to a new study, completing a “handshake” that may show the cells are ready for trials in humans with degenerative eye disorders.

Over a decade ago, researchers from the University of Wisconsin–Madison developed a way to grow organized clusters of cells, called organoids, that resemble the retina, the light-sensitive tissue at the back of the eye. They coaxed human skin cells reprogrammed to act as stem cells to develop into layers of several types of retinal cells that sense light and ultimately transmit what we see to the brain.

Proof of synapses connecting pairs of retinal cells derived from human pluripotent stem cells comes from the red coloring of infection by a modified rabies virus passed from one cell with a yellow nucleus across the synapse to a cell that glows only red

“We wanted to use the cells from those organoids as replacement parts for the same types of cells that have been lost in the course of retinal diseases,” says David Gamm, the UW–Madison ophthalmology professor and director of the McPherson Eye Research Institute whose lab developed the organoids. “But after being grown in a laboratory dish for months as compact clusters, the question remained — will the cells behave appropriately after we tease them apart? Because that is key to introducing them into a patient’s eye.”

During 2022, Gamm and UW–Madison collaborators published studies showing that dish-grown retinal cells called photoreceptors respond like those in a healthy retina to different wavelengths and intensities of light, and that once they are separated from adjacent cells in their organoid, they can reach out toward new neighbors with characteristic biological cords called axons. “The last piece of the puzzle was to see if these cords had the ability to plug into, or shake hands with, other retinal cell types in order to communicate,” says Gamm, whose new results on successful connections between the cells was published in the Proceedings of the National Academy of Sciences.

Source: https://news.wisc.edu/

A simple eye test that predicts death from cardiovascular disease has been developed by British scientists. It combines artificial intelligence (AI) with scans of the retina – a membrane at the back of peepers that contains light sensitive cells. The technique could lead to a screening programme – enabling drugs and lifestyle changes to be prescribed decades before symptoms emerge. Lead author Professor Alicja Regina Rudnicka, of St George’s University of London, said the test is inexpensive, accessible and non-invasive. People at risk of stroke, heart attack and other circulatory conditions could undergo RV (artificial intelligence enabled retinal vasculometry) during routine visits to the optician.

Prof Rudnicka said: “It has the potential for reaching a higher proportion of the population in the community because of ‘high street’ availability. “RV offers an alternative predictive biomarker to traditional risk-scores for vascular health – without the need for blood sampling or blood pressure measurement. “It is highly likely to help prolong disease-free status in an ever-aging population with increasing comorbidities, and assist with minimising healthcare costs associated with lifelong vascular diseases.”

An algorithm called QUARTZ was developed based on retinal images from tens of thousands of Britons aged 40 to 69. It focused on the width, area and curvature, or tortuosity, of tiny blood vessels called arterioles and venules. The performance of QUARTZ was compared with the widely used Framingham Risk Scores framework – both separately and jointly.

The health of all the participants was tracked for an average of seven to nine years, during which time there were 327 and 201 circulatory disease deaths among 64,144 UK Biobank and 5,862 EPIC-Norfolk participants respectively. In men, arteriolar and venular width, tortuosity, and width variation emerged as important predictors of death from circulatory disease. In women, arteriolar and venular area and width and venular tortuosity and width variation contributed to risk prediction.

The predictive impact of retinal vasculature on circulatory disease death interacted with smoking, drugs to treat high blood pressure, and previous heart attacks. Overall, these predictive models, based on age, smoking, medical history and retinal vasculature, captured between half and two-thirds of circulatory disease deaths in those most at risk.

Source: https://www.mirror.co.uk/

The onset of Alzheimer’s disease can be diagnosed by examining proteins in the retina instead of complicated and invasive PET scans or cerebrospinal fluid analysis. Alzheimer’s disease – the progressive neurological disorder that causes the brain to shrink and brain cells to die – is the most common cause of dementia. The disease causes a continuous decline in thinking, behavior and social skills that affect a person’s ability to function independently.

But while the disorder is incurable, it is important to diagnose it as rapidly as possible so measures can be taken to slow the decline. Doctors hope to eventually develop treatments to reduce the risk of developing Alzheimer’s disease.

But now, doctors in the ophthalmology department of the Samson Assuta-Ashdod University Hospital suggest a much simpler way to diagnose Alzheimer’s – by looking for beta-amyloid plaques and abnormal tau proteins in the retina of the eye. The advantage is the accessibility of the retina for direct visualization by non-invasive means.

The retina is a component of the central nervous system that can easily be accessed by technology used routinely by ophthalmologists, they wrote. Photoreceptors in this “screen” at the back of the eye absorb light and transfer data to the retinal ganglion cell layer. Axons (long, slender nerve fibers) in this layer accumulate along the retinal nerve fiber layer and transfer the data to the brain via the optic nerve connected to the eye.

Since the retina is connected to the brain, it seems that changes in this part of the eye reflect pathological processes in the brain, the authors wrote, including the development of Alzheimer’s disease. Amyloid-beta plaques have been found in the retina of cadavers in autopsies of people who died of Alzheimer’s.

Turmeric is a natural, intensely yellow-colored spice that attaches itself to plaques of amyloid-beta. Ten Alzheimer’s patients and six healthy controls were asked to swallow turmeric capsules. A few days later, their retinas were examined. The yellow spice was found to stick to the retinal cells in Alzheimer’s patients but not in the healthy controls. Other non-invasive tests of the retina – including optical coherence tomography and optical coherence tomography angiography – were also conducted and found to point to the early development of Alzheimer’s, the authors wrote. Still, larger tests must be conducted with these means before they can be implemented clinically. A clear biomarker must also be found in the individual to be sure the patient is developing Alzheimer’s and sent for treatments, they concluded.

The research, just published in the latest issue of Harefuah – the Hebrew-language journal of the Israel Medical Association – was conducted by Drs. Keren Wood of the Samson Assuta Ashdod Hospital and Ben-Gurion University of the Negev, Idit Maharshak of Wolfson Medical Center in Holon and Tel Aviv University’s Sackler Faculty of Medicine, and Yosef Koronyo and Maya Koranyo-Hamaoui of the Cedars-Sinai Medical Center in Los Angeles, California.

Source: https://www.jpost.com/

A revolutionary new treatment for cataracts has shown extremely positive results in laboratory tests, giving hope that the condition, that currently can only be cured with surgery, could soon be treated with drugs.

According to the World Health Organization (WHO), 65.2 million people worldwide are living with cataracts, the leading cause of blindness and vision impairment worldwide. Cataract is a clouding of the eye lens that is caused by a disorganisation of the proteins in the lens that leads to clumps of protein forming that scatter light and severely reduce transmission to the retina. This often occurs with age, but can also be caused by the eye’s overexposure to the sun or injury, as well as smoking, medical conditions such as diabetes, and some medications. 

Surgery can correct the condition by replacing the lens with an artificial one. A team of international scientists, led by Professor Barbara Pierscionek, Deputy Dean (Research and Innovation) in the Faculty of Health, Education, Medicine and Social Care at Anglia Ruskin University (ARU), have been carrying out advanced optical tests on an oxysterol compound that had been proposed as an anti-cataract drug.

Source: https://aru.ac.uk/
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https://www.thebrighterside.news/

Alzheimer’s is an insidious brain disease marked by a slow mental decline that can develop unnoticed for decades before symptoms arise, but hidden signs of the condition might exist much sooner. A simple eye test may make diagnosing the earliest stages of ‘diseases of old age’ possible when people are much younger, University of Otago  researchers in New Zeland hope.

Parts of our retina have previously been proposed as biomarkers for Alzheimer’s, but researchers from Otago’s Dunedin Multidisciplinary Health and Development Research Unit have been investigating the retina’s potential to indicate cognitive change earlier in life.

Study lead Dr Ashleigh Barrett-Young says diseases of old age, such as Alzheimer’s, are usually diagnosed when people start forgetting things or acting out of character.

“This is often when the disease is quite far along. Early detection is possible through MRI or other brain imaging, but this is expensive and impractical for most.

“In the near future, it’s hoped that artificial intelligence will be able to take an image of a person’s retina and determine whether that person is at risk for Alzheimer’s long before they begin showing symptoms, and when there is a possibility of treatment to mitigate the symptoms,” she says.

The study, published in JAMA Ophthalmology, analysed data from 865 Dunedin Study participants looking specifically at the retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) at age 45.

Source: https://www.otago.ac.nz/

Using deep learning to predict “retinal age” from images of the internal surface of the back of the eye, an international team of scientists has found that the difference between the biological age of an individual’s retina and that person’s real, chronological age, is linked to their risk of death. This ‘retinal age gap’ could be used as a screening tool, the investigators suggest.

Reporting on development of their deep learning model and research results in the British Journal of Ophthalmology, first author Zhuoting Zhu, PhD, at Guangdong Academy of Medical Sciences, together with colleagues at the Centre for Eye Research Australia, Sun Yat-Sen University, and colleagues in China, Australia, and Germany, concluded that in combination with previous research, their study results add weight to the hypothesis that “… the retina plays an important role in the aging process and is sensitive to the cumulative damages of aging which increase the mortality risk.”

Estimates suggest that the global population aged 60 years and over will reach 2.1 billion in 2050, the authors noted.

“Aging populations place tremendous pressure on healthcare systems.”

But while the risks of illness and death increase with age, these risks vary considerably between different people of the same age, implying that ‘biological aging’ is unique to the individual and may be a better indicator of current and future health. As the authors pointed out, “Chronological age is a major risk factor for frailty, age-related morbidity and mortality. However, there is great variability in health outcomes among individuals with the same chronological age, implying that the rate of aging at an individual level is heterogeneous. Biological age rather than chronological age can better represent health status and the aging process.”

Several tissue, cell, chemical, and imaging-based indicators have been developed to pick up biological aging that is out of step with chronological aging. But these techniques are fraught with ethical/privacy issues as well as often being invasive, expensive, and time consuming, the researchers noted.

Source: https://www.genengnews.com/

Protein deposits in retina and brain appear to parallel possible neurodegeneration, an insight that might lead to easier, quicker detection. Amyloid plaques are protein deposits that collect between brain cells, hindering function and eventually leading to neuronal death. They are considered a hallmark of Alzheimer’s disease (AD), and the focus of multiple investigations designed to reduce or prevent their formation, including the nationwide A4 study.

But amyloid deposits may also occur in the retina of the eye, often in patients clinically diagnosed with AD, suggesting similar pathologies in both organs. In a small, cross-sectional study, a team of researchers, led by scientists at University of California San Diego School of Medicine, compared tests of retinal and brain amyloids in patients from the A4 study and another study (Longitudinal Evaluation of Amyloid Risk and Neurodegeneration) assessing neurodegeneration risk in persons with low levels of amyloid.

Like the proverbial “windows to the soul,” the researchers observed that the presence of retinal spots in the eyes correlated with brain scans showing higher levels of cerebral amyloid. The finding suggests that non-invasive retinal imaging may be useful as a biomarker for detecting early-stage AD risk.

Amyloid deposits tagged by curcumin fluoresce in a retinal scan.

“This was a small initial dataset from the screening visit. It involved eight patients,” said senior author Robert Rissman, PhD, professor of neurosciences at UC San Diego School of Medicine. “But these findings are encouraging because they suggest it may be possible to determine the onset, spread and morphology of AD — a preclinical diagnosis — using retinal imaging, rather than more difficult and costly brain scans. We look forward to seeing the results of additional timepoint retinal scans and the impact of solanezumab (a monoclonal antibody) on retinal imaging. Unfortunately we will need to wait to see and analyze these data when the A4 trial is completed.”

The findings published in the journal Alzheimer’s & Dementia.

https://ucsdnews.ucsd.edu/

Transferring lab grown neurons into animal brains reduces the cells’ viability — their chances of integrating well into the tissue — and the efficiency with which they can restore function. So scientists at Shanghai Research Center for Brain Science and Brain–Inspired Intelligence fashioned a method to regenerate neurons inside the brain. The method is similar to how one would revive a dying plant: by nurturing it with the right conditions for it to grow new leaves.

Building up on a previous study, Haibo Zhou, a postdoctoral researcher in Hui Yang’s lab, and colleagues, set up a method to convert non neuronal brain cells called “glia” into neurons. They did this by turning down a gene called PTBP1 in glia of different parts of the mouse brain, using the gene-editing tool CRISPR. Depending on which brain region was targeted, the glia gave rise to different kinds of neurons.

Reducing PTBP1 levels presumably reverted glia to unspecified stem cells, which adopted varied neuronal identities based on which glia were targeted and the environmental signals they received. This was evident from the team’s successful attempts at restoring two different types of neurons and alleviating the symptoms associated with the loss of each.

Parkinson’s disease occurs due to loss of dopamine-producing neurons and manifests as tremors, stiffness, and loss of balance. To test their method in rejuvenating this group of neurons, the team first got rid of them using a toxic compound in mice. The authors then converted glia into dopamine-producing neurons, and the new cells showed the same activity as their original counterparts.

This rescue was not limited to just the neuron population. It also partially restored the normal motor behavior of the animal. This is a huge step forward from drug induced alleviation of symptoms because it puts forth a more permanent solution.

The team also tackled retinal diseases caused by death of retinal ganglion cells, or RGCs, which leads to permanent blindness. Turning down PTBP1 in glia of the retina transformed them into RGCs. Astoundingly, these renewed neurons not only responded to light independently, but also sent their projections to the visual cortex correctly, restoring circuit function. This led to a partial recovery of eyesight in the treated mice.

Source: https://www.salon.com/

Researchers  find a new structure by which cells in the retina communicate with each other, regulating blood supply to keep vision intact. A new mechanism of blood redistribution that is essential for the proper functioning of the adult retina has just been discovered in vivo by researchers at the University of Montreal Hospital Research Centre (CRCHUM).

“For the first time, we have identified a communication structure between cells that is required to coordinate blood supply in the living retina,” said Dr. Adriana Di Polo, a neuroscience professor at Université de Montréal and holder of a Canada Research Chair in glaucoma and age-related neurodegeneration, who supervised the study.

“We already knew that activated retinal areas receive more blood than non-activated ones,” she said, “but until now no one understood how this essential blood delivery was finely regulated.”

The study was conducted on mice by two members of Di Polo’s lab: Dr. Luis Alarcon-Martinez, a postdoctoral fellow, and Deborah Villafranca-Baughman, a PhD student. Both are the first co-authors of this study.

In living animals, as in humans, the retina uses the oxygen and nutrients contained in the blood to fully function. This vital exchange takes place through capillaries, the thinnest blood vessels in all organs of the body. When the blood supply is dramatically reduced or cut off—such as in ischemia or stroke—the retina does not receive the oxygen it needs. In this condition, the cells begin to die and the retina stops working as it should.

The study has been published in Nature.

https://www.chumontreal.qc.ca/