Investigating doxycycline-loaded biodegradable microparticles

Brief Lay Background

Glaucoma is a disease often caused by elevated eye pressure that can lead to irreversible sight loss. It affects ~80 million people globally, and this is set to increase to 120 million people by 2040.

Trachoma is an infectious eye condition that usually begins in early childhood and often leads to the eyelashes turning inwards (called trichiasis). Around 140 million people live in communities where the infection is endemic, and around 2 million are at risk of losing their sight.

What these two diseases have in common, is that they both require surgery. In both diseases, scarring of the conjunctiva – a thin clear membrane that protects the eye – limits treatment success. Treatments that can prevent this scarring are urgently needed.

What problem/knowledge gap does it help address

In glaucoma, patients having surgery are usually given anti-cancer drugs to prevent the growth of scar tissue in the conjunctiva. But these drugs are toxic and have considerable side effects which can lead to blindness.

People with trachoma are often treated with eyelid surgery to relieve the pain and scratching of the eye, but in 60% of patients, the scarring comes back within three years.

Professor Bailly has previously shown that a drug called doxycycline, a cheap and widely available antibiotic, prevents scarring in a laboratory model of the conjunctiva – especially if the tissue is inflamed.

They have designed tiny biodegradable capsules loaded with doxycycline that could be delivered into the eye during surgery. They now need to understand more about how the capsules work before they can test if they are effective in patients in clinical trials.

Aim of the research project

This project aims to understand how doxycycline is released into the eye and how this is influenced by cells that cause inflammation, called macrophages.

Key procedures/objectives

1. Using cells from patients who have had surgery, and macrophages grown in the lab, the team will construct a model of the conjunctiva in which to study the effect of doxycycline.
2. They will use high-resolution microscopes to take images of cells in the conjunctiva model, to watch how cells involved in scarring (called fibroblasts) and inflammation (macrophages) interact with each other. The microscopes will follow the live movement of the cells and how these movements change when doxycycline capsules are added.
3. In the final part of the project, they will study the breakdown of the biodegradable particles and release of the doxycycline drug, and how this is related to inflammation levels inside the conjunctiva model. 

Potential impact on people with sight loss

If successful, this project will provide essential data to help researchers refine the doxycycline capsule treatment, ensuring it is effective enough to be progressed towards clinical trials. This could lead to a new treatment that prevents scarring during surgery for glaucoma and trachoma and, ultimately, could prevent many millions of people from losing their sight.