Testing a new drug that tackles inflammation in the eye
Research details
- Type of funding: Project Grant
- Grant Holder: Professor Maria Balda
- Institute: UCL Institute of Ophthalmology
- Region: London
- Start date: October 2016
- End Date: September 2018
- Priority: Treatment
- Eye Category: Ocular inflammatory
Overview
Several common eye conditions involve damage to cells in the outer lining (epithelium) or inner lining (endothelium) of different compartments in the eye. For example in the corneal epithelium, which lines and protects the surface of the eye, or in the retinal pigment epithelium, which forms a barrier to the blood at the back of the retina.
Cell damage may be due to long-term swelling (chronic inflammation) from infection, injury, eye cancer, diabetes and age-related conditions.
Professor Balda and team have identified a substance that is overactive in the inner and outer linings of the cornea and retina in eye conditions that involve inflammation. They have also developed eye drops containing a drug that targets the substance. The drops reduce inflammation in mice with a version of allergic conjunctivitis (a condition that affects the lining of the eyelids).
In this project the team is finding out how well the drug reduces inflammation in the retina. They want to find out what the right dose is, when and how best to deliver it and about whether it is safe. Results from the study will provide vital information that’s needed before the drug can progress on to being tested in human clinical trials.-
Scientific summary
A drug target for ocular inflammatory diseases
Epithelia and endothelia form cellular barriers that separate body compartments. Examples are the corneal epithelium, protecting the eye’s surface, and the retinal pigment epithelium (RPE), a barrier to the blood at the back of the retina and vasculature. Epithelial and endothelial defects are major components of common diseases, such as inflammation, infections, diabetes and age-related conditions.
The team has identified a driver of inflammatory processes as well as epithelial and endothelial degeneration. Adult tissues such as the cornea and the RPE express little, if any, under normal conditions; but its expression is upregulated due to pathological stimuli, such as TNF-alpha, TGF-beta and lipopolysaccharide. Thus, this protein represents an ideal drug target. The have developed peptide inhibitors for this target to specifically block disease-induced signalling in in vitro models of ocular diseases. They have also obtained preliminary data that the developed inhibitors can attenuate inflammatory disease in vivo using a mouse model for allergic conjunctivitis. The team has established that the developed inhibitors applied as eye drops to the ocular surface have a comparable inhibitory potency and efficacy as they do in vitro to block target function.
This study is to determine the effectiveness of the developed inhibitors to attenuate retinal inflammatory disease in a model for uveoretinitis. The team will obtain optimal routes of administration and times for treatment, as well as concentrations and toxicity. These in vivo data will support refinement of the inhibitors and their development towards clinical trials for common ocular diseases