Norepinephrine-induced RHOB is a key regulator of circadian intraocular pressure rhythm
Photo by Cottonbro on Pexels
Glaucoma is an eye disease that causes progressive damage to the optic nerve, leading to loss of sight. One major risk factor is an increase in intraocular pressure (IOP), or the pressure inside the eye. This pressure fluctuates throughout the day and is known to rise at night. However, the detailed molecular mechanisms on why this happens have not been fully understood.
Using human cells and mouse models, researchers at Kyushu University have found a new molecular pathway that explains why IOP increases at night. The neurotransmitter norepinephrine (also known as noradrenaline) increases the levels of a molecule called RHOB in the eye’s drainage system called the trabecular meshwork. This weakens the eye’s ‘cleaning function’, resulting in increased IOP. The team expects these findings will lead to the development of new approaches for the early detection of glaucoma, as well as new treatments for controlling IOP by targeting RHOB. Their results were published in the journal Communications Biology.
IOP is maintained by balancing fluid production and fluid drainage within the eye. As with many bodily functions, it is regulated by the circadian clock. In the case of the eye, IOP increases at night. Elevated IOP is a key factor in identifying the onset of glaucoma, but because pressure tends to be lower during the day, regular checkups can potentially miss these warning signs.
Because the circadian clock regulates IOP, disruptions to a person’s internal clock can lead to increased risk of glaucoma. This is why there is a higher risk of glaucoma in the elderly whose body clocks are desynchronising.
Fig.1. Graphical abstract of the research results Using mice, researchers found that norepinephrine released from the sympathetic nervous system increases RHOB levels and suppresses the eye’s drainage system, thereby contributing to the rise in intraocular pressure at night.
“Previous studies have found that signals from the sympathetic nervous system contribute to the nighttime rise in eye pressure, but that underlying process was not well understood,” explains first author of the study, Associate Professor Keisuke Ikegami from Kyushu University’s Faculty of Agriculture. “Most of the fluid in the eye is drained through a tissue called the trabecular meshwork. These cells also help keep the drainage pathway clear by taking up and removing small particles and waste. We also know that norepinephrine is a chemical that is released by the sympathetic nervous system. We decided to investigate how norepinephrine can change the function of fluid drainage in the eye and whether it can explain why eye pressure increases at night.”
The team began by exposing human and mouse trabecular meshwork cells to norepinephrine and compared changes in their genetic activity. They identified 18 genes that increased in both systems and focused on one called RHOB. RHOB is a molecule that is involved in controlling cell shape, movement, and intracellular transport.
Norepinephrine increased RHOB in the trabecular meshwork cells, and when RHOB was removed from human cells, their ability to take up and clear particles increased. In contrast, increasing RHOB reduced the cleaning activity and fluid movement in the eye. Testing in mice, the team used eye drops that inhibit a chemical pathway that controls RHOB activity, the RHO-ROCK pathway. The results showed that the eye drops reduced the nighttime rise in eye pressure.
While these results are not intended for immediate clinical application, they have identified the RHOB pathway as a new potential target for suppressing nocturnal increase in IOP. While ROCK inhibitors are used in glaucoma treatments today, further verification is needed to determine the most effective time of day for administration and how they alter IOP rhythm.
“Loss of vision from glaucoma occurs slowly, so early detection is crucial. We hope our work will lead to new treatment regimens and strategies for administering medicines to achieve the greatest effect,” concludes Ikegami.
Dr Hennie Hamilton with his wife Sylivia and son near their home in Ingwavuma in northern KwaZulu-Natal. (Photo: Halden Krog/Spotlight)
By Sue Segar for Spotlight
As a young doctor working in rural KwaZulu-Natal, Hennie Hamilton lived with a Zulu family for four years, an experience which, he says, changed him forever. Twenty-three years later, he’s still working in the area as medical manager at Mosvold Hospital and doing cataract surgery on patients from five rural hospitals.
In the corner of a small ward in a rural hospital in northern KwaZulu-Natal, an elderly woman with a plastic shield covering her left eye sits up in bed. Her daughter, seated on a chair beside the bed, is holding her hand.
There’s silence, an air of quiet anticipation as a tall doctor leans over the woman and, in deep concentration, slowly removes the eye shield and the eye pad underneath it.
Next, the doctor gently eases her eye open and looks closely into her face to see her response. “Uya bona, Mama?” (Can you see, Mama?) Dr Hennie Hamilton asks the woman, keeping a hand on her shoulder.
The woman, Duduzile Phakathi from Mthubathuba, flickers her eyes. Her grip tightens on her daughter’s hand. “Yebo,” she answers, almost inaudibly, and her face breaks into a smile as she focuses, incredulously, on the tall man in front of her. “Ngiyabonga,” (Thank you) she says. The room erupts into excited chatter as mother and daughter start praying out loud, pouring blessings onto the doctor.
Eye patients from five hospitals – and further
It’s not yet 07:00, and Hamilton, medical manager at Mosvold Hospital in the mountain town of Ingwavuma, is already walking the wards. Every Monday, this quietly spoken man performs cataract surgery on patients from all over the uMkhanyakude district of KwaZulu-Natal. Besides coming from the area served by Mosvold Hospital, patients are referred to him from the other four hospitals in the district – Manguzi, Bethesda, Mseleni and Hlabisa. Tuesdays are for opening the eyes and checking the surgery has been effective.
After losing her sight to cataracts, Duduzile Phakati is overjoyed to see again and get back to caring for her chickens. (Photo: Halden Krog/Spotlight)
As a shaft of morning sunlight beams into the room and onto the faces of the two women, Hamilton, dressed in a black embroidered African work tunic called a Dashiki, explains what he’s doing. He speaks with a strong Afrikaans accent, despite his English last name.
“This patient had what is known as a dense cataract and was completely blind. We operated on her right eye in June, and yesterday we did her left eye. Today, we’re opening the eye and checking whether the operation has been a success,” he says.
A cataract, he explains, is an opacity, or cloudiness, of the lens in the eye, which blocks the passage of light and causes a person’s vision to blur or dim. “It normally happens in old age. Sometimes it arises from diabetes or injuries or trauma, or it can be caused by medication. Some people are born with it, but 95 percent of the patients we see have it because of old age.”
He continues: “Most people will eventually get a cataract. The big difference in this area is that people present very late. In rural areas like this, 20 percent of the patients we operate on are already blind in both eyes. People just wait for longer before they finally come for help.”
Cataract surgery, he says, is a short, painless procedure which involves numbing the eye using eyedrops and an injection; making an incision in the cornea; creating a small “tunnel” on the white of the eye; removing the cataract lens through the tunnel; and then, by folding and inserting it through the incision, replacing the inside of the lens with an artificial lens, made from synthetic material. The incision self-seals and needs no stitches and patients experience an improvement in their vision shortly after the procedure.
“Brought by God himself”
Phakathi’s daughter, Dorothy Mbonambo, says her mother who has diabetes, has been struggling with her eyes for some time. “She was a very busy woman, who loved looking after, and selling her chickens.” But she became totally blind in February, and suddenly she couldn’t do anything for herself.
“We had to feed her, bathe her, and dress her at home, where we all live together. We did not anticipate this at all, and we had to adapt. My mother was really struggling,” says Mbonambo.
Translating for her mother, she continues: “My mother is excited that she can see again. She loves to count her money from selling chickens. It has been frustrating not to be able to do that. She can’t wait to get back to her business, to her normal life.”
Mbonambo says the family was determined to get their mother to Mosvold Hospital for the surgery. “We knew about Dr Hamilton because people talk about this man who came here when he was young, and speaks isiZulu and does the eyes and other operations too.”
Still holding her beaming mother’s hand, Mbonambo points to Hamilton, saying: “This one was brought by God himself.”
“Before, everything was blank”
Next, Hamilton walks into another ward, bigger than the last, where seven more women who had cataract surgery the day before, are recovering. Similar scenes play out as he removes the eye shields for each woman.
Primrose Gina who works as a porter at Mseleni Hospital, says she started struggling with her eyes about three years ago. As the condition of her eyes worsened, it became increasingly difficult to see, and she was told it was cataracts.
After three years of struggling with her vision, Primrose Gina celebrates a new beginning following cataract surgery. (Photo: Halden Krog/Spotlight)
As Hamilton opens her eyes, she lets out an exhilarated shout and tells him she can see.
Gwendolin Mthethwa, a teacher from Ndumo, says her eyes still feel “cloudy” after her operation. This, Hamilton explains, is because, besides the cataract, she also has glaucoma in both eyes.
“Glaucoma is a disease of the optic nerve at the back of the eye which is caused by a build-up of fluid pressure inside the eye, causing damage to the nerve, often due to natural drainage systems being faulty.
“The difference between glaucoma and cataracts is that, with glaucoma, if the damage has happened to the nerve, we cannot reverse it,” Hamilton explains. “We can only try and prevent it from getting worse. But for a cataract, a patient can go from blindness to normal vision again.”
A busy day in the life of a medical manager
It’s nearly 08:00 and Hamilton has already seen eight eye patients. As he strides through the large female ward, the room erupts into song as nurses and some patients gather in the communal ward. “Every morning, we pray together, to connect with the Lord before we start our duties,” a nurse explains.
Next up is a meeting with the hospital’s CEO, Dr Bernard Mung’omba. As part of the hospital’s senior leadership team, Hamilton is closely involved in audits for the provincial health department and overall hospital decisions. As medical manager, he oversees medical care for patients – supervising the doctors, allied health professionals and all other departments including the pharmacy and the hospital’s social workers.
The 186-bed hospital employs 17 doctors and serves seven clinics and a community health centre in the uMkhanyakhude district. The area is characterised by poverty, with many people relying on grants and government work opportunities and living in mostly rural homesteads. Unemployment, teenage pregnancy and substance abuse are big challenges.
As a rural hospital, Hamilton says, “we do bits of everything”. “Last night, I was on call and at 23:30, was in theatre doing a caesarean section.” As medical manager, he says he plays less of a frontline than an advisory role, helping with emergencies from ectopic pregnancy to premature babies, and appendicitis. “We also deal with many diabetic and hypertensive-related emergencies like heart failure, and see many strokes, among older people,” he says.
“The spectrum is extremely wide. We’re a team of people with different strengths and we all rely on one another,” he says.
But it’s the eye operations which he says he finds most rewarding. “Ag, I love it … it gives me so much joy,” he says. “The patients often bless me. They say, ‘may God bless you’. I’m often in tears in the morning when I open their eyes.”
A long history
Mosvold Hospital was founded in 1908 by Christian missionaries and started out as a small stone rondavel. It was taken over by Scandinavian missionaries in the 1930s. The hospital is named after a Norwegian nurse, Esther Mosvold, who worked there in the 1940s, fell in love with the area, and raised money through her wealthy shipping family to expand the hospital. In 1978, the then Natal provincial government took over the hospital and the mission doctors slowly departed.
Hamilton shows us the original stone clinic next to an old chapel which, he says, resignedly, is now used for storage; and a house once lived in by missionaries, which is now the admin office. He points to a site where the provincial government is building a children’s ward and a lodge for mothers to stay while visiting children in hospital; and, on the other side of the hospital, a complex of 40 bachelor flats being built for staff at a cost of R400 million. The project should be completed next year, he says, adding it will be a “gamechanger” for Mosvold. “Mothers visiting their children in hospital currently sleep on mattresses on the floor.”
On our tour, we visit the ward where Hamilton’s eldest child was born in 2007. “It’s grown so much since then,” he says. Around us, the different departments – therapy, dental, radiography, and the pharmacy – are all bustling. In the children’s ward, manager Noziphe Gumbi says they’re seeing way fewer burn wounds this year. “We’ve really focused on outreaches to educate people on the dangers of burns among children,” she says.
Hamilton says he has seen many changes at Mosvold over the years, the biggest being the number of staff. “We’ve almost doubled the number of doctors, so we can spend much more time with patients. There was a time when there were only four doctors. Now, with 16, sometimes 17 doctors, we don’t have to run, run, run like we used to,” he says. “When I arrived, we were only white doctors, now I’m the only white doctor here which helps a lot in terms of language and knowing the people.”
A life in medicine
Hamilton was born in Johannesburg and studied medicine at Pretoria University. In 1997, he started his internship at McCord Hospital, then a mission hospital, in Durban. In 1998, he moved to Bethesda Hospital where, he learnt how to be “an all-round doctor”. He went on to complete qualifications in obstetrics and orthopaedics and trained to do cataract surgery at Edendale Hospital.
He worked at Bethesda at a time when HIV was “completely overwhelming”, he says. A large part of his work was supporting HIV patients clinically and he started a home-based care programme there. In 2003, he met his wife, Sylvia, a Swiss nurse, who, having previously worked in northern KwaZulu-Natal, had returned to start a home-based care programme at Mosvold. They married four months after meeting, and Hamilton moved to Mosvold in 2003, eventually becoming medical manager in 2015.
Why he stayed
“While I was working at McCord’s Hospital in 1997, I met another doctor, Colin Pfaff, who was working at Manguzi Hospital, who was living with a Zulu family,” Hamilton recalls. “When Colin told me about his experience, something just jumped in me. I believe it was God. I realised this was what I wanted to do.”
Less than a year later, while working at Bethesda Hospital, Hamilton moved in with the Nhlekos. “I lived in a mud hut with no running water or electricity. The house was about six kilometres from Bethesda and I’d cycle up and down the mountain to work every day. I became part of the family. In the evenings, I’d sit in the kitchen with my gogo. I learnt to speak fluent isiZulu.
“It was an amazing time, even though it was only for four years. It was the most beautiful place on earth,” he says.
Hamilton shuts his eyes and says: “This experience changed me forever. I was raised very much in an Afrikaner setting. During my high school, our family moved to a farm in the Free State. We lived completely separate from black people, eating from different plates, using separate toilets. There was always this issue of race which I just accepted.”
He continues: “Living with an isiZulu family completely changed that. They gave me a Zulu name, Sandiso, which means spreading God’s grace. People still call me ‘Mgilitsha’, the clan name for the Nhlekos. I learnt to see all people as people, to trust, and to love. It was a heart thing, the most life-changing part of my life.”
Researchers at the University of Gothenburg and Sahlgrenska University Hospital have conducted the first randomised clinical trial in the world to test cortisone eye drops to slow the progression of serious eye disease in extremely premature babies. The results suggest that the intervention can reduce the need for invasive treatment for Retinopathy of prematurity (ROP), a disease that causes blindness in 35 000 children worldwide each year.
ROP occurs when the blood vessels in the retina develop abnormally in very premature babies. In severe cases, laser treatment or injections into the eye are currently required to prevent vision loss and blindness. These treatments are invasive and destructive, and children who require treatment are at the greatest risk of blindness and visual impairment.
The Swedish multicentre study DROPROP involved 100 children born before 30 weeks of pregnancy. The children had a severe but not yet treatment-requiring form of ROP and were randomised to receive either dexamethasone eye drops or placebo.
Large clinical effect
The results showed that 20 percent of the children who received dexamethasone developed treatment-requiring ROP, compared with 38 percent in the placebo group. This corresponds to a 47 percent reduction in relative risk. The difference did not reach statistical significance but showed a large clinical effect.
“The results are very promising because the treatment is simple, inexpensive and non-invasive. In a significant proportion of children, we were able to reduce the need for laser and ocular injections in very fragile premature babies”, says Ann Hellström, professor at the University of Gothenburg and chief physician at Sahlgrenska University Hospital.
The researchers also closely monitored any side effects. No clinically significant difference in complications was seen between the groups. No clear signs of serious hormonal or metabolic side effects were observed.
Long-term follow-ups
The study, funded by the Swedish Research Council, was conducted at six university hospitals and eight county hospitals in Sweden between 2022 and 2025 and is the first double-blind randomized clinical trial of dexamethasone eye drops in ROP.
The researchers are now planning long-term follow-ups of the children to investigate vision development and possible late effects of the treatment.
“There is a great global need for simpler treatments for ROP, especially in parts of the world where access to specialist care is limited. If eye drops can prevent severe ROP, it could save the sight of many children around the world”, says Ann Hellström.
A Phase 2 feasibility study published today (30 July) in the prestigious Nature Communications Medicine journal has shown that early vitrectomy surgery treatment for acute endophthalmitis can be potentially more beneficial to patients’ vision compared with the current antibiotic-first approach.
This is a bacterial infection, affecting the fluid and tissue inside the eye. It is a rare condition (1 in 1000 to 2000 patients), but is a devastating complication from any form of eye surgery or eye injection, and can lead to sight loss and blindness. Treatment guidelines only exist for cataract treatment, and the conventional approach across ophthalmology has been to repeat intravitreal antibiotic injections during the early phase of the condition, then conduct a vitrectomy if this has not proved effective.
Thirty years ago, research indicated the potential benefits of immediate vitrectomy for patients developing endophthalmitis after cataract surgery, but this is seldom carried out. Since then, the development of small gauge (23-, 25 and 27-) pars plana vitrectomy (PPV), wide-angle viewing systems and the routine use of silicone oil have led to a significant evolution for the procedure. This 21-centre national UK study of 63 patients is the first randomised control trial to evaluate the potential benefits of carrying out the vitrectomy at an early stage, within 48-96 hours of diagnosis of endophthalmitis following any type of invasive eye procedures.
After six months, patients receiving this treatment had a median improvement of 40 letters (range 28-70 letters) compared with those having an initial regime of up to six months of antibiotics (median 13 letters increase in vision, range 0-66 letters). The median improvement for the new approach therefore shows over three times the median sight improvement of the conventional treatment.
Importantly, these improvements came earlier for patients too, bringing relief and recovery from what can be a painful condition as well as removing the psychological shadow of potential sight loss from them sooner. At the six-month cut-off period, this study shows these patients can potentially achieve greater improvements in acuity which, if this endures, further increases the social benefit.
Early vitrectomy also showed lower rates of non-serious adverse events (47% vs 68%) and retinal detachment.
The feasibility of the approach and its acceptability to patients and surgeons were validated by the study team. These promising results are based on a sample of 63 so have relatively low levels of statistical significance, but point to the merits of conducting a larger Phase 3 clinical trial.
Lead author Mahi Muqit, senior vitreoretinal consultant at Moorfields Eye Hospital and associate professor at the Institute of Ophthalmology at UCL, said:
“This important new study shows the potential short-term and long-term potential benefits to patients given an early vitrectomy if they contract endophthalmitis after their eye procedure. As using this intervention at diagnosis shows clear potential to improve clinical outcomes, we now intend to take this forward to a definitive Phase 3 randomised clinical trial that can definitively answer this question.”
New platform paves the way for patient-specific lenses in a single visit to the optometrist
A breakthrough combination of new silicone materials and advanced 3D printing technology developed by University of Waterloo researchers could transform how contact lenses are manufactured.
The award-winning innovation can produce patient-specific contact lenses in as little as 20 minutes, paving the way for specialised lenses to be designed, manufactured and dispensed during a single visit to the optometrist. The technology is described in the journal Materials and Design.
Most contact lenses are manufactured in a limited range of sizes and shapes rather than being custom-made for each person’s eye. While soft lenses are suitable for many wearers, patients with irregularly shaped corneas often require rigid lenses to achieve clear vision. Finding the right fit can require several appointments over weeks or months before patients receive lenses that fit properly and provide the function they need.
Researchers in Waterloo’s Department of Chemistry developed the digital manufacturing platform to address these challenges.
“We are very excited about this work because it brings us closer to contact lenses that are truly personalised,” said Dr Shirley Tang, professor in Waterloo’s Department of Chemistry. “Our technology produces lenses with patient-specific surfaces for a precise fit while delivering the optical clarity and mechanical performance expected of commercial contact lenses.”
The platform combines custom lens design software, a newly developed silicone material, and advanced manufacturing techniques.
Silicone is widely used in contact lenses because it is safe, biocompatible and highly oxygen permeable. However, conventional silicone materials are generally not compatible with 3D printing. To overcome this barrier, the Waterloo team developed a new hydrophilic silicone formulation specifically designed for additive manufacturing while maintaining the properties required for contact lens applications.
“Our software designs a lens with an inner surface that precisely matches the patient’s cornea and an outer surface that provides the required vision correction,” said Dr Sayan Ganguly, Chemistry research associate at Waterloo. “The novel hydrophilic silicone material we created, combined with our manufacturing process, produces smooth, transparent lenses that are comfortable to wear.”
Because 3D-printed objects are built layer by layer, tiny stair-step imperfections can form on curved surfaces and reduce optical clarity and wearer comfort. To address this issue, the team developed an ultra-thin, non-contact coating process that smooths the surface without altering the customised shape of the lens or compromising its optical performance.
Laboratory testing confirmed the lenses are biocompatible and the team is preparing for in vivo studies. Researchers have filed a provisional patent for the hydrophilic silicone material and are preparing a full patent application.
Working with the Centre for Vision and Eye Research (CEVR), a joint research institute of the University of Waterloo and the Hong Kong Polytechnic University, the researchers are advancing the technology toward commercialization.
The project recently received a Gold Medal at the Shanghai International Exhibition of Inventions in June 2026.
A model using 71 proteins associated with retinal degradation could predict risk in diabetics
Plasma proteomic signatures for early risk stratification of diabetic retinal neurodegeneration. Credit: Wei Wang and Huangdong Li / Zhongshan Ophthalmic Center, Sun Yat-sen University (CC-BY 4.0, https://creativecommons.org/licenses/by/4.0/)
An AI-assisted model based on 71 different blood proteins could help doctors better predict retinal degeneration in diabetic patients before symptoms occur, according to a study published June 2nd in the open access journalPLOS Medicineby Huangdong Li from the Guangdong Provincial Clinical Research Center for Ocular Diseases in Guangzhou, China, and colleagues.
More than half a billion people around the world are now affected by diabetes. People with the disease are at risk of different neurodegenerative conditions, including the breakdown of the retina, the part of the eye that detects light, in a condition called diabetic retinal neurodegeneration (DRN). It can cause severe visual impairment and vision loss, and scientists believe that DRN is a “window” into the diabetic degeneration of other parts of the nervous system, including cognitive impairment and dementia, as well as degradation of nerves in peripheral areas like the fingers and toes.
Unfortunately, DRN is only detected after symptoms appear, when damage is already irreversible. To better predict who might suffer from DRN and when, the researchers sampled the blood plasma from 1492 patients in the Guangzhou Diabetic Eye Study with type 2 diabetes who did not yet have DRN, and examined the eyes of 1218 of them through scans over a six-year period. They compared their results with another 502 people with diabetes in the United Kingdom BioBank.
The researchers identified 71 different plasma proteins associated with DRN. The proteins were part of cell pathways for processes like inflammation and cellular maintenance. Using machine learning, the scientists used the protein levels in plasma to develop a predictive model called Pro-DRN which was able to improve on the best-performing model by 26 percent. The scientists have already put the model online to allow doctors to assess the risk. While Pro-DRN is based on plasma protein levels and relies on associations between protein levels and DRN and not direct causes, the authors hope that it could help doctors predict and potentially prevent neurodegeneration, using a simple blood test analysed by AI.
The authors add, “Our study suggests that early retinal nerve damage in diabetes leaves measurable signals in the blood. By combining plasma proteomics, longitudinal retinal imaging, and explainable AI, Pro-DRN may help move diabetic eye care from detecting established damage toward earlier, molecularly informed risk stratification, so that closer monitoring and future neuroprotective interventions can be directed to the people most likely to benefit.”
Groundbreaking research from the University of Houston shows that a single low-dose atropine eye drop can produce daylong effects in managing myopia, or nearsightedness.
Professor of Optometry Lisa Ostrin and postdoctoral researcher Barsha Lal are reporting that even one drop in the eye of low-dose atropine (0.01%–0.1%) produces clear changes in pupil size and focusing ability that persist for at least 24 hours. Importantly, they also found that the drop shows no short-term structural effects on the eye, with only temporary changes in blood flow inside the retina.
Ostrin’s latest research is published in the journal Eye and Vision. It adds to a growing body of vision research from David Berntsen, Golden-Golden Professor of Optometry at the University of Houston, who is co-leading a clinical trial to delay the development of myopia in children by using the atropine drops.
Low concentration atropine is widely prescribed to slow myopia progression in children, yet its short-term retinal and choroidal effects remain incompletely understood. Ostrin’s new study evaluated short-term effects of a range of low atropine concentrations on the length of the eye, the blood vessels in the retina and the thickness of the retina and choroid, which sits just behind the retina. These are important measurements because longer eye length is associated with myopia and as it gets longer, the retina and choroid are stretched.
“These findings indicate that a single instillation of atropine does not alter axial length or retinal or choroidal thickness over 24 hours but may transiently affect superficial retinal perfusion in a time-dependent manner,” said Ostrin.
In the double-masked, randomised study, twenty healthy adults received a single instillation of either a placebo or atropine in the right eye during five separate sessions. Researchers then checked the eye structure, thickness, and length in the central retina both one-hour and 24-hours later.
“Characterising these short-term effects is important for a better understanding of the physiological responses to atropine in clinical and research settings,” said Ostrin who previously published research results of a study investigating the short-term effects of a range of low-dose atropine concentrations on the pupils of young adults. In that study, she found similar results with a single drop of atropine inducing significant changes in the pupils.
Together, the studies indicate that atropine induces early functional and vascular effects in the eye, in the absence of structural change.
“By linking objective ocular responses with subjective visual experience, this work advances our understanding of how atropine works and supports more precise, evidence-based, and individualised approaches to myopia management,” said Ostrin.
Photoreceptor cells in the retina. Credit: Scientific Animations
A new Yale School of Medicine (YSM) study has uncovered surprising new details about how our eyes process what we see.
When we look at something, our visual system breaks down different aspects of the scene – such as colour, contrast, and motion – and processes those components separately. It’s called parallel visual processing and it’s what allows our brains to work out what we’re seeing so quickly.
This separation of information starts in the retina, and scientists have thought that separation is maintained as the information travels through the visual system. But in a study published in Neuron, researchers have found that information channels are more integrated than previously thought. This may help cells process weak visual signals, such as low-light conditions, the researchers say.
“We found that while different channels can deliver their own features, they’re also interconnected by underlying electrical circuitry,” says Yao Xue, PhD, a postdoctoral fellow in the department of ophthalmology and visual science at YSM and the study’s first author.
Untangling bipolar cell signals in the retina
The rods and cones in our retinas detect light and transmit signals to a type of neuron called bipolar cells. In these cells, visual components such as night, day, colour, shape, and contrast begin to separate into more than a dozen parallel channels.
But when researchers zoomed in on bipolar cell synapses, they found these information channels intermingle.
Neurons have two types of synapses: chemical and electrical. At chemical synapses, neurons release chemical messengers known as neurotransmitters that bind to the recipient cell. Electrical synapses, also known as gap junctions, facilitate communication with electric currents. Bipolar cells primarily communicate through chemical synapses.
The researchers found, however, that in the mouse and human retinas they studied, electric synapses were integrating most of those seemingly separate bipolar cell information channels. When the scientists electrically stimulated one bipolar cell, instead of seeing a localised release of neurotransmitters just within that cell’s channel, they observed cloud-like patterns of signalling – suggesting crosstalk among the different types of cells.
“When we stimulated one bipolar cell, many bipolar cells released neurotransmitters,” says Z. Jimmy Zhou, PhD, Professor of Ophthalmology and Visual Science and principal investigator.
“If the signal is already very weak and is divided into several channels, there isn’t much left for each channel to process. The integration is particularly useful for detecting low contrast signals or signals from very small objects.”
To their surprise, they also identified one type of bipolar cell, called BC6, that drove this signalling. These cells generated strong signals that travelled through the parallel channels in a hierarchical manner. “People had assumed that the different types of bipolar cells were more or less autonomous,” Zhou says. “But we found a driver among all these cell types that creates this network with a hierarchy.”
Having distinct parallel channels can help bipolar cells divide and conquer as they process different parts of a visual signal. The linkage of these channels through electrical synapses, on the other hand, could help the cells process weak visual signals, the researchers say.
“If the signal is already very weak and is divided into several channels, there isn’t much left for each channel to process,” says Seunghoon Lee, PhD, a research scientist in the department of ophthalmology and visual Science at YSM and co-corresponding author of the study. “The integration is particularly useful for detecting low contrast signals or signals from very small objects.”
“And the cells aren’t cooperating in a random way,” adds Xue. “There’s a commander within them – BC6 – that leads them in relaying signals to the downstream target.”
Recording from hard-to-reach cells
For the study, the researchers used several methods to study the synaptic circuitry of bipolar cells, including imaging to observe the cells’ activity and how they released and responded to neurotransmitters, as well as stimulating activity in bipolar cells and recording responses in recipient cells.
One challenge of studying signal transmission in bipolar cells is that they live in the middle of the retina. Previous studies have cut the retina into slices in order to access the cells, but that can disrupt the synaptic circuitry. In the new study, however, the researchers were able to apply the dual patch-clamp technique in fully intact mouse retinas. This method uses electrodes to stimulate activity in different types of bipolar cells and records the responses of recipient cells.
“No other lab in the world has been able to pull off these kinds of recordings systematically,” says Zhou. “It is a tour de force of Yao Xue’s PhD thesis work, pairing an innovative approach with exceptional electrophysiological skill.”
The team then repeated the experiment in human retinas, which they obtained from the department of pathology’s Legacy Tissue Donation Program. These are the first experiments of their kind in an intact human retina, the YSM researchers say.
Access to good eye care in South Africa remains uneven, resulting in many conditions being diagnosed too late. World Optometry Week, observed from 22 to 28 March, shines a light on this reality, where one in 10 South Africans suffers from some form of vision loss, highlighting the importance of eye health and the role early detection plays in preventing avoidable vision loss.
This challenge is exacerbated by the fact that, while there are approximately 4 200 registered optometrists in South Africa, only a small proportion practise in the public sector. This limits access to care for many communities and delays diagnosis, particularly in under-resourced areas. As a result, prevention remains one of the most important, yet underutilised, tools in protecting eye health.
“The reality is that many serious eye conditions develop without noticeable symptoms early on,” says Dr Themba Hadebe, Clinical Executive at Bonitas. “By the time vision is affected, the condition may already be advanced. Regular eye tests are critical in detecting issues early and preventing avoidable vision loss.”
This year’s World Optometry Week theme, “A Shared Vision: Collaboration in Global Eye Care”, underscores the need for a coordinated approach to improve access, strengthen prevention and enable early diagnosis. This is one way to ease pressure on the broader healthcare system, since identifying conditions earlier reduces the likelihood of more complex interventions later, benefiting both patients and providers.
Why early detection matters
Conditions linked to chronic illnesses, particularly diabetes, remain a significant contributor to vision loss in South Africa. Diabetic retinopathy is among the leading causes of blindness in working-age adults, yet it often develops without pain or early warning signs.
Advances in optometric technology are beginning to shift how the risks of permanent damage are identified and managed. Developments highlighted by the American Optometric Association point to a growing role for AI-assisted diagnostics and enhanced imaging in improving both the speed and accuracy of screening. These tools support clinicians by flagging potential abnormalities during routine eye tests, enabling earlier referral for further assessment where needed.
Within this context, collaboration between medical schemes and provider networks plays a role in strengthening preventative care. Through its partnership with PPN, Bonitas provides members with access to diabetic retinopathy screening as part of the eye testing process at participating network practices.
The screening process uses AI-assisted technology to evaluate retinal images in real time, flagging any irregularities that could indicate early-stage disease. This allows clinicians to identify potential issues ranging from diabetic retinopathy to glaucoma or macular degeneration before they progress to more serious stages. Patients who require further assessment are referred for secondary care, ensuring timely intervention and reducing the risk of irreversible vision loss.
“This approach extends the reach of early detection by combining advanced technology with coordinated care and helps make the most of the limited number of specialists available,” says Hadebe. “Spotting problems early dramatically improves outcomes while reducing pressure on our healthcare system. In practice, it means a member could walk into a routine check-up and leave with peace of mind, or if something is flagged, a clear path to treatment.”
As World Optometry Week highlights, awareness must translate into action. In a healthcare environment where access is not equal, regular eye tests, particularly for those at higher risk, remain essential to safeguarding vision and improving long-term health outcomes.
University of Pittsburgh School of Medicine researchers have developed an early-stage, experimental “living eye drop” that uses a naturally occurring eye bacterium to support corneal wound healing.
The proof-of-‑concept study, published in Cell Reports, demonstrates that the harmless eye-dwelling microbe Corynebacterium mastitidis can be genetically modified to secrete an anti-inflammatory therapeutic that promotes healing following corneal injury in a mouse model.
“This is the first demonstration that a microbe that lives on the ocular surface could be engineered to deliver a therapeutic that improves eye health,” said senior author Anthony St. Leger, associate professor of ophthalmology and of immunology and a faculty member of the UPMC Vision Institute. “It opens the door to the idea of ‘living medicine’ for the eye – something you apply once, and it stays, protects and helps the tissue heal.”
Because tears continually wash medications away, treating ocular surface disease often requires multiple daily applications of eye drops. This can limit the effectiveness of therapies for conditions such as corneal abrasions or dry eye disease.
To explore an alternative delivery method, the Pitt team engineered C. mastitidis, a benign bacterium that naturally resides under the eyelid, to continuously secrete cytokine interleukin10 (IL10). In mice, corneas that were gently scratched and treated with the engineered bacteria healed faster than those treated with regular bacteria or saline. When the IL10 receptor was blocked, this benefit disappeared – confirming the therapeutic effect was IL10-dependent.
The researchers also created a version of the microbe that releases human IL10, which improved wound closure in lab-grown cells that make up the outermost layer of human cornea and reduced inflammatory signaling in human immune cells. These studies offer an initial indication that the approach could eventually be adapted for use in people, though substantial development remains.
“What makes this exciting is that the system is modular,” St. Leger explained. “We built it so you can swap in different genes – different cytokines, growth factors or other proteins – to tailor the therapy to specific eye diseases.”
Though promising, the technology is still in early development. The researchers note that many steps must be completed before any clinical translation is possible, including developing built-in “off switches” to safely and reliably remove or deactivate the engineered bacteria after they are no longer needed.
