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The retina places a large energy demand on the body, in part due to the activity of photoreceptors.

These specialized cells are responsible for receiving light and transmitting visual information to the brain.

Photoreceptor death is the cause of vision loss in many retinal diseases, and there are no effective therapies that improve their survival.

In a paper published in eLife, University of Michigan researchers studied the dependence of photoreceptors on glutamine.

Their results indicate that maintaining the balance of amino acids in these cells is important for photoreceptor health.

The energy requirements of photoreceptors make them vulnerable to small changes in metabolism.

Previous studies focused on glucose as the primary fuel source for these cells.

Currently, therapy that exploits photoreceptor dependence on glucose is being tested in a clinical trial for patients with retinal degeneration.

“Photoreceptors are one of the most metabolically demanding cells in the body, which led us to wonder whether they depend on fuel sources other than glucose for their survival,” said Thomas Wubben, M.D., Ph.D., assistant professor of ophthalmology and visual sciences.

“We looked at glutamine because it is the most abundant amino acid in the blood.”

Glutamine feeds into several pathways, helping cells build other amino acids, including glutamate and aspartate, protein and DNA.

To confirm glutamine’s role in vision, the researchers used mice that lacked the enzyme glutaminase, which breaks down glutamine into glutamate.

They compared these mice to control mice by measuring the thickness of their retinas.

Mice that lacked glutaminase had a rapid reduction in retinal thickness with loss of photoreceptor number and function.

Glutamine plays a role in several cellular processes.

To understand why glutamine is important to photoreceptor survival, the team measured the levels of different molecules in control mice and those that lacked glutaminase.

When mice lacked the enzyme, they had lower levels of glutamate and aspartate.

These amino acids, in turn, help the cells build proteins that are required for photoreceptor function.

The researchers also found that decreased amino acid levels activated the integrated stress response, which is known to trigger cell death if it remains active for too long.

When they inhibited the stress response, the team found that the retinal thickness increased.

“We are now focused on understanding which pathways depend on glutamine and whether they can be targeted by drugs or supplements,” Wubben said.

Glutamine to glutamate conversion pathways are negatively impacted in models of human retinal disease.

“It is possible that resetting metabolism can help prevent vision loss and blindness.”

Reference:

Moloy T GoswamiEric WehShubha SubramanyaKatherine M WehHima Bindu DurumutlaHeather HagerNicholas MillerSraboni ChaudhuryAnthony AndrenPeter SajjakulnukitLi ZhangCagri BesirliCostas A LyssiotisThomas J Wubben (2025) Glutamine catabolism supports amino acid biosynthesis and suppresses the integrated stress response to promote photoreceptor survival eLife 13:RP100747. https://doi.org/10.7554/eLife.100747.3

Sweat does more than just cool down an overheating body. Measuring the chemical makeup of an individual’s sweat-specifically the levels of chloride, a chemical component of salt-can serve as an early warning system to help inform the diagnosis of cystic fibrosis, a genetic disease that damages the lungs and digestive system.

A group of researchers at Penn State recently developed a wearable device capable of accurately tracking chloride ion levels in sweat, which is essential for evaluating hydration status and health conditions like cystic fibrosis and more. Their sensor allows for real-time tracking of an exercising person’s sweat through a hydrogel-based design that allows the device to operate with enhanced sensitivity, accuracy and efficiency, all while being reusable. Their research, available online, is set to publish in the November issue of Biosensors and Bioelectronics.

“The traditional method of measuring chloride ion levels is to go to a hospital and have the measurements taken, which is time consuming and expensive,” said Wanqing Zhang, a doctoral candidate in engineering science and mechanics and co-author of the paper. “The wearable sensors we developed process sweat and track chloride ion levels in real time, directly on a subject’s body. This gives researchers a lot of information about an individual’s health and, specifically for this study, can identify the high chloride ion levels that signify the presence of cystic fibrosis.”

Wearable sensor technology is not new, with several other devices-including those that detect specific biomarkers in sweat-originating just from research at Penn State. However, Zhang explained how different existing designs face different major issues. Colorimetric based sweat sensors, which change color depending on the presence of a specific chemical or reaction, cannot produce reversible readings. If the sensor detects high chloride ion levels, it cannot revert to a neutral state and measure low levels, meaning that researchers can only take one accurate reading before needing to apply a new sensor. Another design, known as a potentiometric sweat sensor, operates by measuring the potential energy difference between two electrodes. While these sensors offer continuous monitoring, they typically have a limited sensitivity and rely on expensive ion-selective membranes to function.

According to Zhang, the research team’s new sensor uses multiple types of hydrogel — a water-rich, gel-like material made of networks of connected molecules called polymers — to address these issues simultaneously.

The team’s sensor contains a sweat chamber, a cation-selective hydrogel (CH) with mobile cations and a high salinity hydrogel (HH) with high salt content like sweat. When sweat enters the chamber, the difference in salt concentration between the sweat and the HH causes the mobile cations in the CH to move from the HH side to the sweat chamber side, generating open-circuit voltage (OCV) between the two points. By tracking this voltage — which indicates how many chloride ions are present in the sweat sample — they can track the levels of chloride ions.

“In other sensor designs, it is extremely difficult or impossible to effectively track small fluctuations in the chloride ion levels,” said Huanyu “Larry” Cheng, the James L. Henderson, Jr. Memorial Associate Professor of Engineering Science and Mechanics and corresponding author on the paper. “By incorporating two different types of hydrogel into the design of our sensor, we can measure the change in OCV across the sensor in real time, meaning we can follow the fluctuation of chloride ion levels in our subject’s sweat.”

However, using just these hydrogel solutions posed some issues, Zhang explained. Hydrogel material is a network of hydrophilic polymers, or materials highly attracted to water, meaning that water and electrolytes could easily pierce into the gels. The team used a material, known as PVDF-HFP film, to isolate their hydrogels from excess water or electrolytes that could negatively impact the sensor’s accuracy.

“This was the primary challenge we faced during development — when we were using just the two types of the hydrogel, water would cause the gel to swell, degrading performance,” Zhang said. “By using the PVDF-HFP film like a barrier between the hydrogel, we were able to protect the hydrogel from excess water, so it could effectively stabilize and facilitate OCV.”

To test the sensor, the team conducted two different experiments. They first collected sweat from a subject exercising and analyzed it using the sensor separately from the subject’s body. They then monitored the sweat as the subject wore the sensor while exercising, tracking chloride ion levels in a software that graphs information in real time. The readings of both experiments were then compared to confirm the accuracy of the sensor’s readings.

The sensor collects data very quickly, measuring and visualizing chloride ion levels in under 10 seconds. According to Zhang, the sensor is significantly more sensitive than existing sensors, producing readings with an accuracy of 174 millivolts per decade – nearly triple the theoretical limit of 59.2 millivolts per decade seen in potentiometric sensors. In addition to excellent reversibility, Zhang explained how the sensor’s high consistency and independence from past readings ensures easy, accurate readouts without having to make connections between multiple past readings, improving reusability.

While their sensor was primarily designed to help identify chloride ion levels indicative of cystic fibrosis, Cheng said he believes the design is a strong foundation for future wearable devices that could sense other biomarkers.

“This sensor has opened the door for low-cost, scalable and wearable chloride sensors,” Cheng said. “We believe that the mechanics used in our design can be adapted to reversibly monitor other ions or chemical compounds that appear in sweat, like glucose, which would provide additional insight on a subject’s health. The mechanics could also be expanded to different applications and platforms beyond just wearable devices, which we are exploring now.” 

Reference:

Wanqing Zhang, Xianzhe Zhang, Ankan Dutta, Farnaz Lorestani, Md Abu Sayeed Biswas, Bowen Li, Abu Musa Abdullah, Huanyu Cheng, Hydrogel-based sweat chloride sensor with high sensitivity and low hysteresis, Biosensors and Bioelectronics, https://doi.org/10.1016/j.bios.2025.117805.