Category: Ophthalmology

Repurposed Drug Combination Promising in the Treatment of Retinal Degenerations

Retina and nerve cells. Credit: NIH

An international team of researchers have tested a combination treatment incorporating three existing drugs and successfully slowed disease progression in pre-clinical retinopathy models. Their results, which used tamsulosin, metoprolol and bromocriptine are published in Nature Communications.

Drug repurposing refers to the use of existing drugs to treat diseases or conditions which they were not originally developed or approved for, and offer a strategy to treat rare diseases for which new drug development is too costly. The new study focused on drug repurposing in the context of inherited retinal degenerations, IRDs. IRDs are a group of genetic diseases that cause the deterioration of retinal anatomy and function, leading to gradual loss of vision and often blindness. Most IRDs are currently inaccessible therapeutically, comprising an unmet medical need for a substantial population worldwide.

A combination treatment incorporating three drugs slowed disease progression 

The researchers found that a combination treatment incorporating three drugs significantly slowed disease progression and decreased disease manifestation in four different animal models of IRD. The combination included the blood pressure and heart failure drug metoprolol, and tamsulosin, which is used for the treatment of benign prostatic hyperplasia, as well as the nowadays less commonly used Parkinson’s disease drug bromocriptine.

“In drug repurposing, it does not matter to which diseases or conditions the drugs were originally developed for, but it is the molecular-level effects of drugs, or pharmacology, that count,” says first author Dr Henri Leinonen, currently Adjunct Professor of Neuropharmacology at the University of Eastern Finland.

In retinal degenerations, intracellular secondary messengers such as cyclic adenosine monophosphate and calcium are believed to be overactive, exacerbating the disease. Metoprolol, tamsulosin and bromocriptine suppress the activity of these secondary messengers via their own distinct cell membrane-receptor actions.

“We hypothesised that the combined effect of these drugs would alleviate the disease, which it indeed did in several distinct animal models of IRDs. However, the efficacy and safety of this combination in humans with retinal degeneration is not guaranteed, and controlled clinical trials to test these are needed,” Dr Leinonen notes.

It is noteworthy that none of the drugs used in the study were effective against retinal degeneration on their own; instead, their combination was necessary for efficacy. According to Dr Leinonen, the same phenomenon may apply to many diseases that are currently untreatable, and especially in multifactorial diseases, effective treatment may require multiple drugs to be used simultaneously.

Drug repurposing could provide solutions especially for the treatment of rare diseases

Rare diseases, IRDs included, are seldom of major interest for the pharmaceutical industry due to a lack of economic incentives. But drug repurposing, actively researched in academia, is a promising method to find solutions for rare diseases that remain therapeutically inaccessible.

The most significant advantages of drug repurposing can be found in faster drug development times and lower costs. Since repurposed drugs have already undergone several mandatory safety tests and early stages of clinical trials, their market entry is considerably faster and cheaper than that of completely new drugs. Drug safety is also an important aspect, as the relative safety of repurposed drugs compared to a completely new chemical reduces risks and uncertainty, which is often considered the most critical point in the drug development process.

Source: University of Finland

In New Study, Supplements Slow Late-stage Age-related Macular Degeneration

Retina showing reticular pseudodrusen. Although they can infrequently appear in individuals with no other apparent pathology, their highest rates of occurrence are in association with age-related macular degeneration (AMD), for which they hold clinical significance by being highly correlated with end-stage disease sub-types, choroidal neovascularisation and geographic atrophy. Credit: National Eye Institute

In a new analysis of data, researchers at the National Institutes of Health (NIH) have found that taking a daily supplement containing antioxidant vitamins and minerals slows progression of late-stage dry age-related macular degeneration (AMD), potentially helping people with late-stage disease preserve their central vision.

Age-related macular degeneration affects the macula, the part of the retina that provides central vision.

Researchers reviewed the original retinal scans of participants in the Age-Related Eye Diseases Studies (AREDS and AREDS2) and found that, for people with late-stage dry AMD, taking the antioxidant supplement slowed expansion of geographic atrophy regions towards the central foveal region of the retina. The study was published in the journal Ophthalmology.

“We’ve known for a long time that AREDS2 supplements help slow the progression from intermediate to late AMD. Our analysis shows that taking AREDS2 supplements can also slow disease progression in people with late dry AMD,” said Tiarnan Keenan, MD, PhD, of NIH’s National Eye Institute (NEI) and lead author of the study. “These findings support the continued use of AREDS2 supplements by people with late dry AMD.”

In their new analysis, the researchers reviewed the original retinal scans of participants in the AREDS (total 318 participants, 392 eyes) and AREDS2 (total 891 participants, 1210 eyes) trials who developed dry AMD, calculating the position and expansion rate of their regions of geographic atrophy. For those people who developed geographic atrophy in their central vision, the supplements had little benefit. But for the majority who developed geographic atrophy far from the fovea, the supplements slowed the rate of expansion towards the fovea by approximately 55% over an average of three years.

In early and intermediate AMD, the light-sensing retina at the back of the eye develops small yellow deposits of fatty proteins called drusen. When the disease progresses to the late stage, people can develop leaky blood vessels (“wet” AMD) or can lose regions of light-sensitive cells in the retina (“dry” AMD). The geographic atrophy in these regions slowly expands over time, causing people to progressively lose their central vision.

The original AREDS trial found that a supplement formula containing antioxidants (vitamin C, E, and beta-carotene), along with zinc and copper, could slow progression of intermediate to late-stage AMD. The subsequent AREDS2 trial found that substituting the antioxidants lutein and zeaxanthin for beta-carotene improved the efficacy of the supplement formula and eliminated certain risks. At the time, neither trial detected any further benefit once participants had developed late-stage disease.

However, that original analysis did not account for a phenomenon in the dry form of late AMD called “foveal sparing.”  While all regions of the retina are sensitive to light, the region that gives us the highest acuity central vision is called the fovea. Many people with dry AMD first develop geographic atrophy outside this foveal region, and they only lose their central vision when the geographic atrophy regions expand into the foveal area.

“Our high acuity central vision is essential for tasks like reading and driving. Given that there are few therapeutic options for people with late-stage dry AMD to retain or restore their vision, antioxidant supplementation is a simple step that may slow central vision loss, even for those with late disease,” Keenan said. “We plan to confirm these findings in a dedicated clinical trial in the near future.”

Learn more about AREDS and AREDS2

Source: NIH/National Eye Institute

Reduced Retinal Cell Oxygen Use in Glaucoma Tied to Faster Vision Loss

Retina and nerve cells. Credit: NIH

Glaucoma occurs when retinal ganglion cells start to die, and the main risk factors are high eye pressure and older age. Currently, all licensed treatments are designed to lower pressure in the eye – also known as intraocular pressure. However, some patients still continue to lose their sight following treatment.

Retinal cells are particularly energy hungry. To help doctors better understand who will lose their vision faster, the new study, published in Nature Medicine, asked whether mitochondrial function, measured in white blood cells, is lower in people with glaucoma than those without glaucoma and if mitochondrial function is associated with the rate at which glaucoma patients lose vision.

The researchers assessed 139 participants who were already receiving treatment to lower intraocular pressure and 50 healthy people acting as a control (comparison) group.

They measured how well cells in the blood use oxygen, how much vision was lost over time and nicotinamide adenine dinucleotide (NAD) levels. NAD is a molecule in the body that helps cells produce energy and is made from vitamin B3 in the diet.

Firstly, the researchers discovered that certain cells in the blood, known as peripheral blood mononuclear cells, use oxygen differently in people with glaucoma. The team measured how much oxygen these cells use and found that people whose blood cells used less oxygen tended to lose their vision faster, even if they were being treated to lower intraocular pressure. This measurement explained 13% of the differences in how fast patients lost vision.

Additionally, people with glaucoma were found to have lower levels of NAD in their blood cells compared to people without glaucoma. These lower NAD levels were linked to the lower oxygen use in the blood cells.

Senior author, Professor David (Ted) Garway-Heath (UCL Institute of Ophthalmology and Moorfields Eye Hospital), said: “White blood cell mitochondrial function and NAD levels, if introduced as a clinical test, would enable clinicians to predict which patients are at higher risk of continued vision loss, allowing them to be prioritised for more intensive monitoring and treatment.

“If further research shows that low mitochondrial function or low NAD levels are a cause for glaucoma, then this opens the way for new treatments.

“UCL and Moorfields Eye Hospital are currently leading a major clinical trial funded by the Medical Research Council and the National Institute for Health and Care Research, to establish whether high-dose vitamin B3 can boost mitochondrial function and reduce vision loss in glaucoma.*

“We hope that this will open a new avenue for treatment of glaucoma patients which does not depend on lowering the eye pressure.”

Source: University College London

Study Reveals Association Between Semaglutide Use and Optic Neuropathy

Photoreceptor cells in the retina. Credit: Scientific Animations

Researchers from Mass Eye and Ear have discovered an association between semaglutide use and an increased risk of nonarteritic anterior ischaemic optic neuropathy (NAION) in patients with type 2 diabetes, overweight or obesity. The findings, which appear in JAMA Ophthalmology, only show an association and cannot establish causation.

Though NAION is relatively rare, occurring in in about 10 in 100 000, it is the second most common cause of optic nerve blindness, behind glaucoma, and it is the most common cause of sudden optic nerve blindness. Caused by decreased blood flow to the optic disc, it usually affects only one eye but in 15% of cases both eyes are involved. There are no treatments for this disease and little prospect for improvement, although it is painless.

The study was led by Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School.

In mid-2023 Rizzo, a resident (study co-author Seyedeh Maryam Zekavat, MD, PhD) and other Mass Eye and Ear neuro-ophthalmologists noticed a disturbing trend – three patients in their practice had been diagnosed with vision loss from this relatively uncommon optic nerve disease in just one week. They did notice however that all three were taking semaglutide.

“The use of these drugs has exploded throughout industrialised countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Rizzo, corresponding author of the study. “It is important to appreciate, however, that the increased risk relates to a disorder that is relatively uncommon.” 

This prompted the Mass Eye and Ear research team to run a retrospective analysis of their patient population to see if they could identify a link between this disease and these drugs.

They performed matched cohort study of 16 827 patients revealed higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–GLP-1 receptor agonist medications for diabetes or obesity.

The researchers found that patients with diabetes who were prescribed and took semaglutide were four times (hazard ratio [HR], 4.28) more likely to be receive a NAION diagnosis. The odds increased to more than seven times (HR, 7.64) when the prescription was for weight control in obesity.

The researchers analysed the records of more than 17 000 Mass Eye and Ear patients treated over the six years since Ozempic was released and divided the patients in those who were diagnosed with either diabetes or overweight/ obesity. The researchers compared patients who had received prescriptions for semaglutide compared to those taking other diabetes or weight loss drugs. Then, they analysed the rate of NAION diagnoses in the groups, which revealed the significant risk increases.

Study limitations include the fact that Mass Eye and Ear sees an unusually high number of people with rare eye diseases, and the number of NAION cases seen over the six-year study period is relatively small. With small case numbers, statistics can change quickly, Rizzo noted. Medication adherence could also not be assessed.

Only correlation can be shown by the study, not causality. How or why this association exists remains unknown. Likewise, the reason for the reported difference between diabetic and overweight groups – but this does not appear to result from a difference in baseline characteristics. The optic nerve is known to host GLP-1 receptors, but the study did not adequately address all the confounding factors. They also caution against generalising the results (from a majority white population) since Black individuals have a lower risk of NAION.

“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is pre-existing significant visual loss from other causes.”

CRISPR Treatment Improves Vision in Inherited Retinal Degeneration

Photo by Jeffrey Riley on Unsplash

About 79% of clinical trial participants experienced measurable improvement after receiving experimental, CRISPR-based gene editing that is designed to fix a rare form of blindness, according to a paper published in the New England Journal of Medicine.

“This trial shows CRISPR gene editing has exciting potential to treat inherited retinal degeneration,” said corresponding author Mark Pennesi, MD, PhD. “There is nothing more rewarding to a physician than hearing a patient describe how their vision has improved after a treatment. One of our trial participants has shared several examples, including being able to find their phone after misplacing it and knowing that their coffee machine is working by seeing its small lights.

Pennesi is an ophthalmologist and Oregon Health & Science University’s lead scientist for the Phase 1/2 BRILLIANCE trial, which evaluated the safety and effectiveness of EDIT-101, an experimental CRISPR-based gene editing treatment developed by Editas Medicine. The experimental treatment was designed to edit a mutation in the CEP290 gene, which provides instructions to create a protein that is critical for sight.

People with this gene mutation have a rare condition that is commonly called Leber Congenital Amaurosis, or LCA, Type 10, for which there is currently no Food and Drug Administration-approved treatment. LCA’s various types occur in about 2 or 3 out of 100 000 newborns.

The OHSU Casey Eye Institute treated the trial’s first participant in early 2020. That procedure also marked the first time that CRISPR had been used to edit genes within the human body, called in vivo gene editing.

The new paper describes the study’s findings through February 2023 and details how the trial’s 14 participants – 12 adults and two children – responded to receiving EDIT-101 in one eye. Key results include:

  • 11 participants, about 79%, showed improvement in at least one of four measured outcomes.
  • 6 participants, about 43%, showed improvement in two or more outcomes.
  • 6 participants, about 43%, reported improved vision-related quality of life.
  • 4 participants, about 29%, had clinically meaningful improvement in visual acuity, or how well they could identify objects or letters on a chart.
  • There were no serious adverse events related to the treatment.
  • Most adverse events were mild or moderate, and all have since been resolved.

Four specific outcomes were used to evaluate the experimental treatment’s effectiveness:

  • Visual acuity
  • How well participants did in a full-field test, which involves seeing coloured points of light while looking into a specialised device
  • How well participants navigated a research maze with physical objects and varying amounts of light
  • How much participants reported experiencing improved quality of life

Further research for a future treatment

In November 2022, trial sponsor Editas Medicine announced that it was pausing the trial’s enrolment and would seek another partner to continue the experimental therapy’s development. Pennesi and colleagues are exploring working with other commercial partners to conduct additional trials, in collaboration with Editas. The researchers hope future studies can examine ideal dosing, whether a treatment effect is more pronounced in certain age groups such as younger patients, and include refined endpoints to measure impacts on activities of daily living.

Source: Oregon Health & Science University

SARS-CoV-2 can Cross the Blood–Retinal Barrier, Infecting the Eyes

Photoreceptor cells in the retina. Credit: Scientific Animations

The blood-retinal barrier is designed to protect vision from infections by preventing microbial pathogens from reaching the retina where they could trigger an inflammatory response with potential vision loss. But researchers at the University of Missouri School of Medicine have discovered that SARS-CoV-2 can breach this protective retinal barrier with potential long-term consequences in the eye. Their findings are reported in PLOS Pathogens.

Pawan Kumar Singh, PhD, an assistant professor of ophthalmology, leads a team researching new ways to prevent and treat ocular infectious diseases. Using a humanised ACE2 mice model, the team found that SARS-CoV-2, can infect the inside of the eyes even when the virus doesn’t enter the body through the surface of the eyes. Instead, they found that when viruses enter the body through inhalation, it not only infects organs like lungs, but also reaches highly protected organs like eyes through the blood-retinal barrier by infecting the cells lining this barrier.

This finding is important as we increase our understanding of the long-term effects of SARS-CoV-2 infection,” said Singh. “Earlier, researchers were primarily focused on the ocular surface exposure of the virus. However, our findings reveal that SARS-CoV-2 not only reaches the eye during systemic infection but induces a hyperinflammatory response in the retina and causes cell death in the blood-retinal barrier. The longer viral remnants remain in the eye, the risk of damage to the retina and visual function increases.”

Singh also discovered that extended presence of SARS-CoV-2 spike antigen can cause retinal microaneurysm, retinal artery and vein occlusion, and vascular leakage.

“For those who have been diagnosed with COVID-19, we recommend you ask your ophthalmologist to check for signs of pathological changes to the retina,” Singh said. “Even those who were asymptomatic could suffer from damage in the eyes over time because of COVID-19 associated complications.”

While viruses and bacteria have been found to breach the blood-retinal-barrier in immunocompromised people, this research is the first to suggest that the virus that causes COVID-19 could breach the barrier even in otherwise healthy individuals, leading to an infection that manifests inside the eye itself. Immunocompromised patients or those with hypertension or diabetes may experience worse outcomes if they remain undiagnosed for COVID-19 associated ocular symptoms.

“Now that we know the risk of COVID-19 to the retina, our goal is to better understand the cellular and molecular mechanisms of how this virus breaches the blood-retinal barrier and associated pathological consequences in hopes of informing development of therapies to prevent and treat COVID-19 induced eye complications before a patient’s vision is compromised,” Singh said.

Source: University of Missouri-Columbia

Newly Found Retinal Cells may Paint a Complete Picture of Colour Vision

Photo by Jeffrey Riley on Unsplash

Scientists have long studied just how the eye’s three cone photoreceptor types work together to allow humans to perceive colour. In a new study in the Journal of Neuroscience, researchers at the University of Rochester used adaptive optics to identify rare retinal ganglion cells (RGCs) that could help fill in the gaps in existing theories of colour perception.

The retina has three types of cones to detect colour that are sensitive to either short, medium, or long wavelengths of light. Retinal ganglion cells transmit input from these cones to the central nervous system.

In the 1980s, David Williams, the William G. Allyn Professor of Medical Optics, helped map the “cardinal directions” that explain colour detection. However, there are differences in the way the eye detects colour and how colour appears to humans. Scientists suspected that while most RGCs follow the cardinal directions, they may work in tandem with small numbers of non-cardinal RGCs to create more complex perceptions.

Recently, a team of researchers from Rochester’s Center for Visual Science, the Institute of Optics, and the Flaum Eye Institute identified some of these elusive non-cardinal RGCs in the fovea that could explain how humans see red, green, blue, and yellow.

“We don’t really know anything for certain yet about these cells other than that they exist,” says Sara Patterson, a postdoctoral researcher at the Center for Visual Science who led the study. “There’s so much more that we have to learn about how their response properties operate, but they’re a compelling option as a missing link in how our retina processes colour.”

Adaptive optics peer past the eye’s natural distorations

The team took advantage of adaptive optics, which uses a deformable mirror to overcome light distortion and was first developed by astronomers to reduce atmospheric blurring in ground-based telescopes. In the 1990s, Williams and his colleagues began applying adaptive optics to study the human eye. They created a camera that compensated for distortions caused by the eye’s natural aberrations, producing a clear image of individual photoreceptor cells.

“The optics of the eye’s lens are imperfect and really reduce the amount of resolution you can get with an ophthalmoscope,” says Patterson. “Adaptive optics detects and corrects for these aberrations and gives us a crystal-clear look into the eye. This gives us unprecedented access to the retinal ganglion cells, which are the sole source of visual information to the brain.”

Patterson says improving our understanding of the retina’s complex processes could ultimately help lead to better methods for restoring vision for people who have lost it.

“Humans have more than 20 ganglion cells and our models of human vision are only based on three,” says Patterson. “There’s so much going on in the retina that we don’t know about. This is one of the rare areas where engineering has totally outpaced visual basic science. People are out there with retinal prosthetics in their eyes right now, but if we knew what all those cells do, we could actually have retinal prosthetics drive ganglion cells in accordance with their actual functional roles.”

Source: University of Rochester

A New Treatment for Retinal Detachment – Based on Seaweed

Photoreceptor cells in the retina. Credit: Scientific Animations

In Korea, it is taboo to consume seaweed soup before exams since it there is a belief that the slippery nature of seaweed can lead to slipping up in the exam and failing. The slick surface of seaweeds is attributed to alginate, a mucilaginous carbohydrate substance. Now, Korean researchers have made use of this substance in the treatment of retinal detachment.

The result is an artificial vitreous body for treating retinal detachment, based on alginate from seaweed.

The research findings were recently published in Biomaterials, an international journal of biomaterials published by Elsevier. The work was a collaborative effort between Professor Hyung Joon Cha from the Department of Chemical Engineering and the School of Convergence Science and Technology and Dr. Geunho Choi from the Department of Chemical Engineering at Pohang University of Science and Technology (POSTECH), and Professor Woo Jin Jeong, Professor Woo Chan Park, and Professor Seoung Hyun An from the Dong-A University Hospital’s Department of Ophthalmology.

The vitreous body is a gel-like substance that occupies the space between the lens and retina, contributing to the eye’s structural integrity. Retinal detachment occurs when the retina separates from the inner wall of the eye and moves into the vitreous cavity, leading to detachment and potentially resulting in blindness in severe cases.

While a common approach involves removing the vitreous body and substituting it with medical intraocular fillers like expandable gas or silicone oil, these fillers have been associated with various side effects. To address these concerns, the research team employed a modified form of alginate, a natural carbohydrate sourced from algae.

Alginate, also known as alginic acid, is widely utilised in various industries, including food and medicine, for its ability to create viscous products. In this research, the team crafted a medical composite hydrogel based on alginate, offering a potential alternative for vitreous replacement.

The hydrogel has high biocompatibility and optical properties akin to authentic vitreous body, preserving the vision of patients post-surgery. Its distinctive viscoelasticity effectively regulates fluid dynamics within the eye, contributing to retinal stabilisation and the elimination of air bubbles.

To validate the hydrogel’s stability and effectiveness, the team conducted experiments using rabbit eyes, which closely resemble human eyes in structure, size, and physiological response.

Implanting the hydrogel into rabbit eyes demonstrated its success in preventing the recurrence of retinal detachment, maintaining stability, and functioning well over an extended period without any adverse effects.

Professor Hyung Joon Cha of the POSTECH who led the study remarked, “There is a correlation between retinal detachment and severe myopia and the prevalence of retinal detachment is increasing, particularly in young people. The incidence of retinal detachment cases in Korea rose by 50% in 2022 compared to 2017.” He expressed the team’s commitment by saying, “Our team will enhance and progress the technology to make the hydrogel suitable for practical use in real-world eye care through ongoing research.”

Professor Woo Jin Jeong from the Dong-A University Hospital stated, “The worldwide market for intraocular fillers is expanding at a rate of 3% per year.” He added, “We anticipate that the hydrogel we’ve created will prove beneficial in upcoming vitreoretinal surgeries.”

Source: Pohang University of Science & Technology (POSTECH)

Trial of Minocycline for Dry Age-related Macular Degeneration Flops

Retina showing reticular pseudodrusen. Although they can infrequently appear in individuals with no other apparent pathology, their highest rates of occurrence are in association with age-related macular degeneration (AMD), for which they hold clinical significance by being highly correlated with end-stage disease sub-types, choroidal neovascularisation and geographic atrophy. Credit: National Eye Institute

The drug minocycline, an antibiotic that also decreases inflammation, failed to slow vision loss or expansion of geographic atrophy in people with dry age-related macular degeneration (AMD), according to a phase II clinical study at the National Eye Institute (NEI), part of the National Institutes of Health.

Dry AMD affects the macula, the part of the retina that allows for clear central vision. In people with dry AMD, patches of photoreceptors and their nearby support cells begin to die off, leaving regions known as geographic atrophy. Over time, these regions expand, causing people to lose more and more of their central vision.

Microglia, immune cells that help maintain tissue and clear up debris, are present at higher levels around damaged retinal regions in people with dry AMD than in people without AMD. Scientists have suggested that inflammation – and particularly microglia – may be driving the expansion of geographic atrophy regions.

This study, led by Tiarnan Keenan, MD, PhD, a Stadtman Tenure-Track Investigator at the NEI’s Division of Epidemiology and Clinical Applications, tested whether inhibiting microglia with minocycline might help slow geographic atrophy expansion and its corresponding vision loss.

The trial enrolled 37 participants at the NIH Clinical Center in Bethesda, Maryland, and at the Bristol Eye Hospital, United Kingdom.

After a nine-month period where the researchers tracked each participant’s rate of geographic atrophy expansion, the participants took twice-daily doses of minocycline for two years.

The researchers compared each participant’s rate of geographic atrophy expansion while taking minocycline to their baseline rate, and found there was no difference in geographic atrophy expansion rate or vision loss with minocycline.

Previous studies have shown that minocycline can help reduce inflammation and microglial activity in the eye, including the retina.

The drug has shown beneficial effects for conditions such as diabetic retinopathy, but has not previously been tested for dry AMD.

Source: NIH/National Eye Institute

In the Fight against Brain Pathogens, the Eyes Have it

Photo by Victor Freitas on Pexels

The eyes have been called the window to the brain. It turns out they also serve as an immunological barrier that protects the organ from pathogens and even tumours, Yale researchers have found. In a new study, researchers showed that vaccines injected into the eyes of mice can help disable the herpes virus, a major cause of brain encephalitis.

To their surprise, the vaccine activates an immune response through lymphatic vessels along the optic nerve.

The results were published Feb. 28 in the journal Nature.

“There is a shared immune response between the brain and the eye,” said Eric Song, an associate research scientist and resident physician in Yale School of Medicine’s Department of Immunobiology and corresponding author of the paper.

“And the eyes provide easier access for drug therapies than the brain does.”

Wanting to explore immunological interactions between brain and eyes, the research team, which was led by Song, found that the eyes have two distinct lymphatic systems regulating immune responses in the front and rear of the eye.

After they vaccinated mice with inactivated herpes virus, the researchers found that lymphatic vessels in the optic nerve sheath at the rear of the eye protected mice not only from active herpes infections, but from bacteria and even brain tumors.

Harnessing this new biology, Song’s team is currently testing newly created drugs from his lab delivered through eye injections that may help combat macular edema, or leaky blood vessels of the retina common in people with diabetes, and glaucoma.

“These results reveal a shared lymphatic circuit able to mount a unified immune response between posterior eye and the brain, highlighting an understudied immunological feature of the eyes and opening up the potential for new therapeutic strategies in ocular and central nervous system diseases,” the authors wrote.

Source: Yale University