Researchers have developed a novel approach to treating corneal injury: genetically engineered bacteria that colonize the eye and deliver anti-inflammatory therapy directly to the ocular surface. The strategy, reported in Cell Reports, uses a modified commensal microbe to release interleukin-10 (IL-10), a cytokine known for its potent immunoregulatory effects, to promote corneal epithelial repair.
Accounting for around 3% of ER visits, corneal wounds affect more than one million people in the United States each year and can lead to infection, scarring, and vision loss if healing is delayed. Although topical medications are commonly used to control inflammation and support repair, they are rapidly cleared from the ocular surface, requiring frequent dosing and limiting sustained therapeutic effects.
To address this limitation, investigators from University of Pittsburgh School of Medicine engineered Corynebacterium mastitidis, a bacterium that naturally colonizes the ocular surface, to act as a long-term therapeutic delivery platform. Using transposon mutagenesis, the researchers identified a native secretion signal within the bacterium that could be harnessed to export proteins outside the microbial cell. This system was then used to engineer the organism to produce and secrete IL-10.
In mouse models of corneal injury, the IL-10–producing microbes significantly accelerated epithelial wound closure compared with controls. The engineered bacteria also reduced local inflammation, highlighting the therapeutic potential of delivering immunomodulatory cytokines directly at the site of injury.
The findings suggest that the ocular microbiome could be harnessed as a “live biotherapeutic” capable of providing sustained delivery of therapeutic molecules. Unlike traditional eye drops, which are quickly diluted or washed away by blinking and tear turnover, colonizing microbes could provide ongoing release of anti-inflammatory agents, perhaps even within a single inoculation.
Beyond corneal wounds, the authors suggest the approach could be adapted to treat a range of ocular surface disorders driven by inflammation, including infectious keratitis, dry eye disease, or immune-mediated corneal pathology. And while the work remains at a preclinical stage, the concept represents a novel intersection of microbiome science, genetic engineering, and ophthalmic therapeutics. By transforming commensal ocular bacteria into targeted drug-delivery vehicles, the approach could offer a new strategy for managing diseases in which sustained local therapy is difficult to achieve.
If translated successfully to humans, engineered ocular microbes may provide ophthalmologists with an entirely new class of treatment – living therapeutics designed to restore immune balance and accelerate tissue repair directly on the eye’s surface.
Accounting for around 3% of ER visits, corneal wounds affect more than one million people in the United States each year and can lead to infection, scarring, and vision loss if healing is delayed. Although topical medications are commonly used to control inflammation and support repair, they are rapidly cleared from the ocular surface, requiring frequent dosing and limiting sustained therapeutic effects.
To address this limitation, investigators from University of Pittsburgh School of Medicine engineered Corynebacterium mastitidis, a bacterium that naturally colonizes the ocular surface, to act as a long-term therapeutic delivery platform. Using transposon mutagenesis, the researchers identified a native secretion signal within the bacterium that could be harnessed to export proteins outside the microbial cell. This system was then used to engineer the organism to produce and secrete IL-10.
In mouse models of corneal injury, the IL-10–producing microbes significantly accelerated epithelial wound closure compared with controls. The engineered bacteria also reduced local inflammation, highlighting the therapeutic potential of delivering immunomodulatory cytokines directly at the site of injury.
The findings suggest that the ocular microbiome could be harnessed as a “live biotherapeutic” capable of providing sustained delivery of therapeutic molecules. Unlike traditional eye drops, which are quickly diluted or washed away by blinking and tear turnover, colonizing microbes could provide ongoing release of anti-inflammatory agents, perhaps even within a single inoculation.
Beyond corneal wounds, the authors suggest the approach could be adapted to treat a range of ocular surface disorders driven by inflammation, including infectious keratitis, dry eye disease, or immune-mediated corneal pathology. And while the work remains at a preclinical stage, the concept represents a novel intersection of microbiome science, genetic engineering, and ophthalmic therapeutics. By transforming commensal ocular bacteria into targeted drug-delivery vehicles, the approach could offer a new strategy for managing diseases in which sustained local therapy is difficult to achieve.
If translated successfully to humans, engineered ocular microbes may provide ophthalmologists with an entirely new class of treatment – living therapeutics designed to restore immune balance and accelerate tissue repair directly on the eye’s surface.
