Development and Translation of Novel Host Defense Peptides for Acanthamoeba Keratitis

Brief Lay Background

Acanthamoeba keratitis (AK) is a rare condition that affects the cornea – the clear front surface of the eye. Acanthamoeba is a single-celled creature, or ‘amoeba’, found in soil and water. If it gets into the eye it can cause serious problems.

Most people who become infected wear contact lenses. Almost half of the people who become infected have sight loss as a result and a quarter eventually need a corneal transplant. The high proportion of people that go onto experience sight loss is primarily due to the delay in diagnosis, limited treatment options, resistance to treatment, and potential changes in the eye known as ‘ocular toxicity’ following long-term use of anti-amoebic treatment.

What problem/knowledge gap does it help address

Successful treatment of Acanthamoeba keratitis requires both the active form (trophozoites) and the inactive form (cysts) to be completely destroyed. However, the cysts are resistant to most antibiotics, biocides and contact lens solution.

Host defence peptides (HDPs), or antimicrobial peptides, are small molecules that play an important role in the immune system, which have shown potential as an antimicrobial treatment. The research team have previously designed a series of hybrid HDPs (by combining two different HDPs into one molecule), which showed good efficacy against bacteria, fungi and Acanthamoeba whilst maintaining the safety.

Aim of the research project

To develop a new HDP-based treatment for AK and examine how the HDPs influence the disease process.

Key procedures/objectives

1. Examine the efficacy of the HDPs against the active and inactive forms of a common type of Acanthamoeba and monitor for toxicity using human corneal and red blood cells.
2. Examine the efficacy and toxicity of the HDPs when used in combination with the currently available anti-amoebic treatment, known to be toxic to corneal cells.
3. Use a model of AK to determine how well HDPs can enter and be retained in corneal cells.
4. Examine changes in the genetic makeup of Acanthamoeba and corneal cells when treated with and without HDPs.

Potential impact on people with sight loss

Corneal infections and antimicrobial resistance are on the rise, meaning new treatment options are in great demand. Developing hybrid HDPs as a new treatment for corneal infection, including AK, that targets the amoeba whilst reducing toxicity on corneal cells has great potential for minimising the impact on quality of life for those affected.