Tag: cornea

Categories : OphthalmologyTags :

Scientists Engineer ‘Living Eye Drop’ to Support Corneal Healing

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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.

Source: University of Pittsburgh

Categories : Immune System OphthalmologyTags :

Contrary to Prior Belief, T Cells Even Protect the Cornea

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Photo by Stormseeker on Unsplash

Researchers have discovered that the immune cells guarding the healthy human cornea from pathogens and inflammation are T cells, and dendritic cells, as previously thought. The discovery, published in PNAS, redefines current understanding of the immune cell landscape in the cornea of a healthy human eye. It builds on the team’s previous research in Cell Reports that showed that T cells protect the eye against virus infection in mice.

The collaborative research team jointly developed a new imaging technique as part of their investigation.

Research leader Professor Scott Mueller, from the Department of Microbiology and Immunology at the Doherty Institute explained that our knowledge of the various immune cell types in the human cornea is important for establishing the eye’s protective mechanisms against pathogens and disease.

“By combining our newly developed imaging technique with other advanced analytical approaches, we were able to discover that a significant number of cells at the surface of the healthy cornea are actually T cells,” said Professor Mueller.

“Until now, these cells were mistakenly classified as dendritic cells based on static imaging. This completely changes the current dogma in the field that only dendritic cells are present in the healthy cornea.”

The study’s first author, University of Melbourne’s Associate Professor Laura Downie said that being able to dynamically capture the cells’ normal behaviour, and in response to inflammation, provides unique understanding into the immune response in the eye.

“Using our non-invasive imaging approach, which we term Functional In Vivo Confocal Microscopy (Fun-IVCM), we have been able to see that these T cells move around quickly and interact with other cells and nerves in the outermost layer of the cornea. We also captured different cell dynamics in response to contact lens wear and in allergic eye disease, and quantified how these behaviours are modulated by drug treatments,” said Associate Professor Downie.

“These findings reshape our understanding of the distinct immune cell subsets in the human cornea, and how they respond to different stimuli. Using Fun-IVCM, we can achieve rapid, real-time insight into the cellular immune responses in living humans, in this accessible peripheral sensory tissue.”

Senior author Dr Holly Chinnery, also of the University of Melbourne, added that the new research will have major implications for the medical and immunology fields, including for patients and practitioners.

“Because this new technique involves non-invasive, time-lapse imaging of the human cornea, Fun-IVCM could be used in clinics directly to assess immune responses and ocular health. It could even be used for general immune system health,” said Dr Chinnery.

“Changes in T cells and behaviour could be used as a clinical biomarker of disease and assist with treatments.”

Source: The Peter Doherty Institute for Infection and Immunity