Developing a human model of the cornea to study keratitis

Dr Esther Karanukaran

University of Sheffield

Animals to be replaced: mice, rats and zebrafish

Keratitis, also known as ‘corneal ulcer,’ is an inflammation of the cornea – the clear, dome shaped window at the front of the eye that covers the iris and pupil. Keratitis affects twenty-three million people globally, each year. It is a condition that is hard to diagnose and without quick intervention, progresses rapidly (within 48 hours in severe cases), leading to painful damage to the cornea and blindness. Keratitis is caused by injury or more commonly by bacterial infection.

One of the obstacles currently facing doctors treating keratitis is the emergence of ‘superbugs’. These are bacteria, viruses, fungi, and parasites that have adapted to medicines. This phenomenon is known as ‘resistance’ and makes infections harder to treat and increases the risk of diseases spreading, severe illness and death. Resistance is a major healthcare challenge as superbugs are outpacing the development of new antibiotics so new, effective treatments for keratitis are urgently needed.

Over 3 million animals were used in experiments last year, with over 66,000 animals used to develop and test new drugs for infectious diseases alone. Mice are most commonly used. Their corneas are cut so that bacteria can be injected into their eyes. Painful corneal ulcers develop along with inflammation and redness of the eye, indicating that the animal is infected. At this point they are not only blind but also sensitive to light, shown through more tears being produced. The infection progresses before a drug is administered, causing a great degree of suffering with the animals ultimately being killed.

Drugs that show promise in these animal eye experiments often fail in human trials or conversely, potentially useful drugs for people, which do not work well in animals, are discarded. One of the key reasons for these failures is that animal and human tissue respond differently to infection and to drugs. Research on keratitis indicates that the infection progresses faster in animals. The production of ‘biofilms’ (where many bacteria stick to a surface together within a matrix) during infection, may be different. Eyes structure and function are also fundamentally different between species, some examples being blink interval, which is 2.8 seconds in humans but over 30 seconds in mice, as well as the composition of tears, which is different in people and animals. A more human relevant approach would not only end animal suffering but provide a more effective solution for people with keratitis.

Dr Esther Karanukaran, at the University of Sheffield, is developing a novel, human-relevant infection model of keratitis that can be used to test and refine potential drugs before they are used in clinical trials. She is using human cornea, deemed unsuitable for corneal transplants, which would otherwise be wasted. By sterilising the corneas with antibiotics (to rid them of bacteria) and then introducing a wound on the corneal surface, she is infecting the cornea with bacteria and monitoring their growth over time. She is also using specialised microscopes to check whether biofilms are formed.

Dr Karunakaran’s model could have a significant impact by entirely removing the need for animal drug testing for keratitis, as well as other eye conditions. It would also help guide the development of more effective antibiotics to tackle superbugs which cause diseases such as keratitis, saving the vision of those affected.