How can we advance our understanding of rare eye conditions?

1. How are we advancing our understanding of retinitis pigmentosa?

The leading cause of sight loss in children and working-age adults is inherited retinal dystrophies (IRDs), such as retinitis pigmentosa (a group of rare eye diseases that affect the retina).

IRDs cause untreatable blindness. They are caused by mutations in over 150 genes that result in the death of photoreceptors at the back of the eye. Research has found gene therapy may potentially be used to treat IRDs, such as Retinitis Pigmentosa.

At present, there is only one form of gene therapy available for one rare eye condition. Results have shown that visual improvement is currently minimal and short-lived. But there is still a need to understand the cause of photoreceptor death and to develop treatments that can be used in combination with or alongside gene therapies.

Fight for Sight awarded funding to a project led by Dr Roly Megaw at the University of Edinburgh that aims to investigate the processes that lead to photoreceptor death and, consequently, IRDs.

More about the project

Below, Professor Megaw explains how he and his team are using cutting-edge AI software to better understand inherited retinal dystrophies, including RP. 

2. Understanding inherited retinopathies

Inherited retinopathies are a group of eye diseases that affect the retina, the light-sensitive tissue at the back of the eye. In people with inherited retinopathies, the light-sensing cells (photoreceptors) in the retina stop working and eventually die – causing progressive sight loss, often leading to blindness.

Faults in the CRB1 gene can cause different inherited retinopathies. It is not understood why specific faults in this gene can cause different retinopathies with such varied patterns of sight loss, meaning healthcare professionals cannot predict the severity or the rate of progression of a person’s sight loss.

Professor Mariya Moosajee at the UCL Institute of Ophthalmology aims to improve our understanding of inherited retinopathies’ natural history (or progression) caused by faults in the CRB1 gene. Fight for Sight are co-funding her research alongside Moorfields Eye Charity. Her research could help determine which patients might benefit from novel gene therapies and other innovative treatments in the future.

Read more about research into CRB1.

3. How can we better understand Leber Hereditary Optic Neuropathy?

Leber Hereditary Optic Neuropathy (LHON) is a genetic condition that affects the optic nerve (which sends visual information to the brain) and causes sudden loss of central vision in both eyes.  

LHON primarily affects young adult men and can begin in one eye or both simultaneously. Over time, vision gradually worsens with a loss of sharpness and colour vision, which can impact people’s ability to perform detail-oriented tasks such as reading and driving.

Four genes have been linked with LHON; these genes interfere with how much energy mitochondria (the powerhouse of the cell) can generate. This leads to the loss of retinal nerve cells and the eventual deterioration of the optic nerve. Vision can sometimes be recovered, which suggests that these nerves are ‘sleeping’ as opposed to ‘lost’ and may be revived.

We are funding a project led by Professor Marcela Votruba at Cardiff University that aims to study retinal cells and identify surviving and dysfunctional cells. The team also want to determine whether these cells can spontaneously recover with the aid of an approved drug, which is suggested to support mitochondrial function.

4. How can we better understand Stargardt disease?

Stargardt disease causes progressive central vision loss due to damage to the macula, a part of the retina. 

Symptoms of the condition generally start in childhood and adolescence and will gradually worsen over time, although symptoms vary from person to person; for some, sight loss might not occur until adulthood.

Gene therapy provides an opportunity to prevent sight loss by delivering a correct copy of the faulty gene into the affected photoreceptor cells and restoring the process of toxic by-product removal.

This therapeutic approach has shown some success in clinical trials, but not in Stargardt disease. This is due to the size of the faulty gene. It is for this reason that we are funding research by Professor Omar Mahroo and Dr Matteo Rizzi at UCL, who have developed a modified tool that can carry larger genes, specifically based on the faulty gene in Stargardt disease.

If successful, this could pave the way for new gene therapies for many other inherited retinal conditions.

5. Understanding retinoblastoma

Retinoblastoma is a childhood eye cancer which usually occurs before the age of three.

The cause is almost always genetic. 

We're funding Dr Amy Gerrish at Birmingham Children's Hospital who is working on a test that will allow researchers to identify Rb in patients who have not had their eye removed. In this webinar, she will spotlight her research, leading to better childhood cancer diagnosis.

Living with retinoblastoma