Inherited Retinal Diseases
Inherited retinal dystrophy (IRD) describes a broad spectrum of genetic disease that affects the light sensing tissue at the back of the eye. As the leading cause of blindness in working-age adults in many countries, IRD represents a major global healthcare burden. In the United States, it is estimated that 350,000-400,000 individuals are affected by IRD.
Retinitis pigmentosa is the commonest form of IRD affecting approximately 1 in 4500 individuals and is characterized by rod photoreceptor degeneration leading to night-blindness and loss of peripheral vision, often subsequently affecting central vision. In contrast, Stargardt disease, caused by variants in the ABCA4 gene, originates in the cells of the central macula leading to central vision loss.
Over 300 genes have been implicated in IRD to date, spanning autosomal dominant, recessive, x-linked and mitochondrial inheritance patterns and affecting a vast array of cellular mechanisms including phototransduction, the visual cycle, ciliary transport, RNA splicing and many different metabolic pathways. Although genetic testing for IRD is relatively advanced, up to 50% of individuals are disappointingly left without a molecular diagnosis even after having the most up-to-date testing available. These missing diagnoses leave patients and families with uncertainty about their prognosis and risks to family members, without access to cascade and family planning testing and crucially excluded from accessing any potential gene targeted therapeutic.
In fact, the very first FDA approved gene replacement therapy available in the United States, Luxterna, targets the retina specific RPE65 gene essential for recycling the visual pigment 11-cis-retinal in the visual cycle. Mutations in this gene cause Leber Congenital Amaurosis, leading to severe vision loss in infancy. Correcting the errors in RPE65 by gene-replacement therapy provides the opportunity to potentially change lives and cure blindness. With the promise of many more gene therapies in development and currently in clinical trial, closing the diagnostic gap is of the utmost importance for ophthalmic geneticists.
The Arno laboratory is a global leader in ophthalmic genetics and genomics. Our interests lie in studying the genomes of people affected by IRD using cutting-edge technologies to advance the understanding of genetic eye disease and narrow the diagnostic gap. Dr. Arno was previously the senior scientist for the Genetics Department at Moorfields Eye Hospital in London, the largest tertiary eye-care hospital in Europe, where he led the genomic analysis of thousands of genetic eye disease patients as part of the UK’s 100,000 genomes project. In the Research Division of Greenwood Genetic Center, Dr. Arno brings over a decade of IRD genetics expertise and leads a number of projects in this area.
Current active projects on IRD in the laboratory include:
- Investigating the utility of long-read sequencing technology for genomic analysis in IRD
- Utilizing various long-read sequencing methods to improve diagnostic outcomes for patients and families
- Functional characterization of non-coding variants in IRD genes by transcript analysis of blood derived RNA
- Novel disease gene discovery projects
- Characterization of IRD-associated hypomorphic alleles found in syndromic disease genes