Fight for Sight’s research round-up 2015
Spotlight on inherited eye disorders, AMD, glaucoma and corneal blindness
Fight for Sight is the UK’s leading charity dedicated to funding eye research. Our current commitment is £8.4 million to projects at 35 academic and medical institutions. Only through medical research can we find ways to prevent, halt or reverse the sight loss that touches every family. Here are just a few of the discoveries our researchers have published in 2015 with full or part-funding from Fight for Sight.
The white of the eye could be key to glaucoma
Dr Craig Boote at Cardiff University has had a busy year in glaucoma research. He’s part of a team that has published several papers that advance what we know about optic nerve damage and the white of the eye (the sclera). The optic nerve sends signals from the eye to the visual brain; its connections pass through pores in the sclera formed between a mesh of collagen fibres. These fibres are sensitive to intraocular pressure. As pressure increases, the fibres deform, changing the shape of the pores. High pressure in the eye is one of the most common risk factors for glaucoma.
The team has found that the sclera stiffens as we age. The collagen that makes up its connective tissue becomes less aligned or more randomly structured in the region nearest the optic nerve head. This age-related increase in stiffness is much greater (by 87%) and happens faster in people with diabetes. The results suggest that diabetes could be protective of glaucoma, at least in the early stages, given that people with diabetes should be more at risk due to higher eye pressure but are in fact less affected by glaucoma. Collagen structure in a healthy eye also depends on its depth within the sclera. This could be important as depth-dependent collagen structure changes in glaucoma.
A possible new clue to age-related macular degeneration
Dr Imre Lengyel at the UCL Institute of Ophthalmology is part of an international team of researchers who have found that tiny lumps of a type of calcium phosphate known as hydroxyapatite (HAP) may be an important trigger for age-related macular degeneration (AMD). HAP is common in the body – it makes up the hard part of teeth and bones – but it had never been identified in this part of the eye before. The discovery could be an important biomarker that would allow early detection of AMD, before significant sight loss has occurred. It may also give a new target for treatment. Fight for Sight part-funded the research via the Mercer Fund.
The best diet for growing stem cells
Dr Andrew Hopkinson and team in the Academic Ophthalmology group at the University of Nottingham have been developing a biological wound dressing that can help prevent corneal blindness, one of the leading causes of treatable sight loss worldwide. As part of their research they’ve discovered that corneal stromal stem cells grown in the lab will turn out very differently depending on which culture medium is used. The culture medium is a liquid or gel that provides nutrients for growing cells. The team has identified the best of 7 culture mediums tested in the study for producing stem cells in a lab dish that are most like stem cells found naturally in a healthy eye. This is a vital new piece of information for researchers aiming to produce a reliable source of suitable cells for cell replacement therapy. Read more about the wider project here.
Eye development genes identified
At the University of Manchester Dr Rachel Gillespie, Prof Graeme Black and team have confirmed the genetic basis of a rare and complex inherited disorder that causes sight loss early in life. People with oculoauricular syndrome (OS) have congenital cataract, iris coloboma, early-onset retinal dystrophy and are at risk of glaucoma and corneal opacity due to anterior segment dysgenesis. The condition is caused by faults in the gene HMX1 and also affects external ear cartilage. HMX1 is a key player in eye development. This is only the second family with OS to have been identified since the condition was first described in 1945.
Their work also contributed to the discovery that the gene SIPA1L3 is critical for the eye to develop normally. Genetic analysis of patients with lens and eye abnormalities, together with analysis in mice and zebrafish, show that faults in SIPA1L3 disrupt the growth, structure, internal organisation and connections of lens epithelial cells. These are the cells that line the outside of the lens, doing maintenance and repair to keep it clear and healthy.
Dr Gillespie earned her PhD supervised by Prof Black in a studentship funded by Fight for Sight. The project has produced significant results including the new genetic test for congenital cataract which was adopted by the NHS in 2014.
Scars in their eyes: the differences between inherited retinal disorders
Dr Rachael Pearson and team at the UCL Institute of Ophthalmology have been working on cell replacement therapy for inherited retinal disorders. They’ve published new research in mice that reveals a wide range of scar-forming activity in the eye by support cells called Müller glia, after the loss of light-sensitive ‘photoreceptor’ cells. Results show that the process of scar formation (gliosis) differs depending on the specific genetic fault causing disease, but apparently not on the stage of disease. These results shed light on why previous cell replacement therapy studies have had variable success at restoring vision. This is a vital step in the process of making the retina more favourable to cell transplantation and, ultimately, to restoring sight in people with inherited retinal disorders.
Developing gene therapy for retinitis pigmentosa
A collaboration between scientists in the UK and the USA has shown that gene therapy can give life-long protection to the light-sensitive photoreceptor cells responsible for colour vision in a mouse model of the most common inherited eye disorder. Results published in the journal Molecular Therapy demonstrate that the preserved cells were able to drive visually-guided behaviour, even in later stages of the condition and despite becoming less sensitive to light. The research was led by Professor Robert MacLaren at the University of Oxford’s Nuffield Laboratory of Ophthalmology and funded in the UK primarily by Fight for Sight.
The RP Genome Project is well underway
Scientists from the University of Leeds, in collaboration with researchers from the Institute of Ophthalmology in London and Ghent University in Belgium, have discovered that faults in the gene DRAM2 cause a new type of late-onset inherited blindness. DRAM2 has a role in initiating a cell-recycling process called autophagy, in which the damaged components of cells are broken down and renewed. The findings suggest that DRAM2 is essential for photoreceptor survival.
This new insight into the condition was only made possible through collaboration between UK and European institutions. In the UK, the £1.2 million RP Genome Project funded by sight loss charities RP Fighting Blindness and Fight for Sight, brings together leading genetic ophthalmology researcher centres in Leeds, London, Manchester and Oxford.
The RP Genome Project also enabled UK and Italian researchers to discover the genetic cause of a rare form of blindness known as ‘inherited retinal dystrophy associated with ocular coloboma’. Babies with the condition are born with a hole in one or more parts of the eye, such as the iris or retina. Results published in the journal PNAS show that a fault in the miR-204 gene is responsible.(12)