Minimising side-effects of drugs for patients with intraocular inflammation

In 2013 the UK’s National Institute for Health Research (NIHR) published a list of priorities
for eye research based on a national consultation exercise conducted through the James
Lind Alliance. The number one priority for patients with ocular inflammatory diseases was to
find better treatments, and especially to find alternatives to the use of steroid drugs which
are limited by wide-ranging side-effects. We are therefore seeking to develop a new therapy
that will minimise the use of steroids in patients with potentially blinding inflammatory eye
diseases.

Ten years ago, the National Eye Research Centre enabled our research team to be the first
to study the effect of steroids on the immune system of patients with inflammatory eye
diseases. This revealed huge variation in peoples’ response to steroids, based on which we
have identified a type of immune cell which escapes the effect of steroids in patients who
experience the most side-effects of treatment. Our goal is to use a new type of medication to
selectively inhibit these steroid resistant cells and therefore minimise the dose of steroids
patients need to control their inflammatory eye disease. To do this we are learning from the
field of cancer medicine which has pioneered the use of a technology called antibody-drug
conjugation. This combines the biological precision of an artificially engineered antibody with
the powerful effects of conventional drugs. Such technologies are very novel and they have
not previously been applied to the treatment of inflammatory diseases.

We have commissioned a leading UK based biotechnology company which specialises in
antibody-drug conjugation (Polytherics Ltd, Abzena Plc) to generate an antibody fragment
which attaches to a protein called CCR6 on the surface of steroid resistant immune cells,
and to link this to a drug which we have shown strongly inhibits steroid resistant cells. In this
proposal, we are seeking to conduct experiments that will test in principle whether this new
drug conjugate can suppress human steroid resistant cells in the laboratory and also in
specialised mice that have human immune systems. If this is successful we will seek further
funding from the UK Medical Research Council for full pre-clinical development of the drug
conjugate for inflammatory eye diseases.

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Research Funding Programmes & Application Procedures

Developing new treatment of inflammatory eye disease

Dr Mark Young and his team at Cardiff University are looking at preventing cell death to treatment inflammatory eye disease
Potential new treatments for non-infectious inflammatory eye disease

Dr Lindsay Nicholson, University of Bristol is investigating endothelial activation in uveitis
Developing eye drop treatment for diabetic retinopathy

Prof David Bates at University of Nottingham is investigating the role of SRPK1 inhibitors in diabetic retinopathy.
The role of microglia in inflammatory eye disease

Prof Andrew Dick at University of Bristol is researching plasticity of microglia during intraocular inflammation
A novel treatment for autosomal dominant optic atrophy

Prof Marcela Votruba at Cardiff University is looking for a novel treatment for blindness caused by autosomal dominant optic atrophhy
Investigating genetic changes in dry age-related macular degeneration

Dr Louise Porter - University of Liverpool is investigating the epigenetic changes associated with dry age-related macular degeneration
Regenerating retinal ganglion cells to restore sight

Prof Keith Martin (University of Cambridge) is investigating the manipulation of P13K signalling to enhance regeneration of retinal ganglion cells.

Glaucoma

Glaucoma is the most common cause of sight loss amongst those of working age. Pressure is raised in the eye which damages the optic nerve and increasingly causes sight loss. New treatments, including improved eye drops and surgical techniques to reduce this pressure in the eye are being researched.
Age-related macular degeneration

600,000 people in the UK currently have sight loss caused by AMD and around 70,000 new cases are diagnosed every year.
Cataracts

Cataracts occur when changes in the lens of the eye cause it to become less transparent. This results in cloudy or misty vision. Cataracts are the leading cause of blindness globally but can be easily treated.
Uveitis

Uveitis is a leading cause of visual impairment in people of working age in the UK. It is an inflammation of the middle layer of the eye, called the uvea or uveal tract.
Dry Eye Syndrome

Dry eye syndrome, or dry eye disease, is a common condition that occurs when the eyes don't make enough tears, or the tears evaporate too quickly. This leads to the eyes drying out and becoming red, swollen and irritated. Dry eye syndrome is also known as keratoconjunctivitis sicca.
Corneal Dystrophy

Corneal dystrophy is a collective term that refers to several conditions that cause damage to the cornea. The cornea is the clear tissue at the front of the eye that lets in light and helps focus it on the retina so that we can see.
Retinitis pigmentosa

Retinitis pigmentosa (RP) is the name given to a group of inherited conditions of the retina that all lead to a gradual progressive reduction in vision.
Amblyopia

A lazy eye, also known as amblyopia, is a childhood condition that occurs when the vision in one eye does not develop properly.
Funding Schemes
Who we are and what we do

The National Eye Research Centre is a leading eye research charity that funds eye research teams across the UK to find the causes of eye disease to develop new prevention methods and more effective treatments. We fund research for eye diseases in both adults and children.