Superstars of STEM: Looking inflammation in the eye

Uveitis, or inflammation inside the eye, can lead to pain, sensitivity to light, blurred or obscured vision, and in extreme cases – especially when it involves the retina – can lead to blindness.

Like rheumatoid arthritis, the condition is due to an excess of white blood cells inside the eye, which are controlled by adhesion molecules. One very important adhesion molecule in the retina is called Intercellular Adhesion Molecule 1, or ICAM-1.

ICAM-1 lines the retinal blood vessels, picks up white blood cells and helps them enter the retina itself. In most instances this is useful, because the cells detect and attack any harmful viruses or bacteria that might have strayed in, but when too many move in, serious inflammation is the result.

Controlling the ICAM-1 could be the key to stopping uveitis in its tracks, and Justine Smith, a world-leading ophthalmologist based at Flinders University in South Australia, is working hard to discover how a drug could be developed to target it.

Currently, treatments for the condition, which is essentially a disorder of the immune system, often involve taking an immunosuppressive medication, which makes the person more susceptible to serious infections.{%recommended 7297%}

Smith’s team has found a possible alternative: rather than preventing white blood cells from entering the retina, which stops their ability to protect against infection, it is possible to decrease the amount of ICAM-1 and thus simply reduce the cell intake.

“This targeted approach means that the immune system isn’t compromised, and the problem is treated at its source,” explains Smith.

“The body is still free to fight off infection and disease, and we are able to limit the movement of white blood cells to avoid inflammation.”

The way Smith is doing this is by controlling transcription factors – which are proteins that control the amount of a given molecule produced by a cell. In this case, the transcription factor governing the production of ICAM-1 is knocked out.

Smith’s team is now testing the treatment, using eye tissue gifted from Australian organ donors.

“We are very lucky in Australia, as many people donate their eyes for cornea transplants after they die, and many also opt to gift the parts of the eye that remain after the transplant to research,” Smith says.

“We are testing this treatment on tissue that has been gifted by different people, and soon we will have an understanding of how we can control ICAM-1 in any eye that is affected by uveitis.”

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Justine Smith is among 30 Superstars of STEM featured in this weekly series prepared by Science & Technology Australia (STA). To learn more about the program, visit the STA website.