Welcome to Retina-IRD
Transforming Lives through Research and Innovation in Inherited Retinal Diseases
About Us
Retina-IRD is a pioneering organization committed to understanding, diagnosing, and treating inherited retinal diseases (IRDs). Our mission is to bring hope and vision to those affected by these conditions through cutting-edge research, clinical advancements, and community support.
Retina International's IRD Toolkit
On behalf of Retina International, I would like to welcome you to the IRD Toolkit. This educational resource was designed by patients for patients, their representatives and their healthcare professionals to address the challenges of vision health and avoidable blindness.
The objective of this toolkit is to give you an overview of Inherited Retinal Diseases (IRDs), including descriptions of on-going research, clinical trials and new treatments of the various diseases, and associated patient advocacy. We will continually update and add to this resource as our understanding evolves. IRDs are a collection of rare retinal degenerations, such as Retinitis Pigmentosa (RP), Usher Syndrome, Leber Congenital Amaurosis (LCA), Stargardt Disease, and Juvenile Macular Degenerations. They represent the primary cause of severe visual impairment or blindness in childhood and those of working age in industrialised countries. To date, more than 280 genes have been associated with IRDs, covering 60 to 70% of all cases. Work continues to discover more. For the large majority of these rare diseases no treatment is currently available, however many clinical trials are underway giving hope for the future. Given the breadth of information, we will launch with an initial focus on LCA and Usher Syndrome and follow with other conditions. The recent approval of the first gene therapy for LCA due to biallelic mutations in the RPE65 gene gives rise to a growing demand for more information for those affected, their families and professionals alike. We hope that this toolkit is useful and look forward to your feedback and suggestions. Enjoy your visit, Christina Fasser, President, Retina International
How eyes work
Light (from the sun or an artificial light source) travels in a straight line. It bounces off objects and into our eyes. Light first passes through the cornea, the clear, dome-shaped surface that covers the front of the eye. The cornea bends (refracts) the incoming light, which then passes through the pupil. The iris, the coloured part of the eye, regulates the size of the pupil by stopping too much light entering the eye when it is bright and maximising the amount of light entering the eye when it is dark. The light then passes through the lens, which focuses the light onto the back surface of the eye, the retina. The eye changes the shape of the lens as we look at far or near objects to keep them in focus – this is called accommodation.
The retina is the thin, delicate, light-sensitive tissue that lines the back of the eye. It contains “photoreceptor” cells that convert light into electrochemical signals. The signals are processed and travel from the retina to the brain through the optic nerve, a bundle of about one million nerve fibres. The brain processes the signal to create the image that you see. The image received on the retina is actually upside-down – as an infant, our brains learn to invert the image so we don’t get confused.
The retina consists of a neural layer and a pigmented layer. The neural layer contains photoreceptor cells, the rod and cone cells. These cells collect the light signals directed onto them and send them as electrical signals to the optic nerve. Further details of the cell types found within the neural layer of the retina are provided below.
Rod Cells: Rod cells are concentrated around the edge of the retina. They help us to see things that aren’t directly in front of us, giving us a rough idea of what is around us. They help us with our mobility and getting around, by stopping us from bumping into things. They also enable us to see things in dim light and to see movement.
Cone Cells: Cone cells are concentrated in the centre of our retina where the light is focused by the cornea and lens. This area is called the macula. Cone cells give us our detailed vision which we use when reading and looking at people’s faces. They are also responsible for most of our colour vision.
Retinal Pigment Epithelium (RPE): The retinal pigment epithelium is a layer of cells located just outside the retina and is attached to the choroid
Bipolar Cells: Bipolar cells exist between photoreceptors (rod cells and cone cells) and ganglion cells. They act, directly or indirectly, to transmit signals from the photoreceptors to the ganglion cells.
Ganglion cells: Is a type of nerve cell located near the inner surface of the retina of the eye. It receives visual information from photoreceptors and communicates this to the brain.
What Are Inherited Retinal Diseases?
Inherited retinal diseases (IRDs) are a group of genetic disorders that affect the retina's ability to function properly, leading to progressive vision loss and, in some cases, blindness. Common IRDs include retinitis pigmentosa, Leber congenital amaurosis, and Stargardt disease.
Purpose of this toolkit
This toolkit aims to provide information about IRDs to inform and educate people with IRDs, their carers, and the medical and research community with the goal of empowering all stakeholders to advance towards cures.
Information about clinical trials that are currently being conducted worldwide can be found on www.ClinicalTrials.gov and can be searched by condition and trial location.
Genetics of Inherited Retinal Diseases
IRDs are caused by a gene mutation that is inherited from a parent. This led to the title of “Inherited Retinal Disease”. In the case of IRDs, the mutation affects genes that play an essential role in normal retinal development and functioning, leading to the degeneration of photoreceptors and other retinal cells and associated vision loss.
Scientific research has shown that IRDs are genetically diverse, with over 260 disease-related genes identified to date. In some cases the genes or mutations responsible are not yet known or not understood. However, ongoing research and genetic testing is advancing our knowledge of such genetic changes in order to find cures.
Genetic testing is of utmost importance for many IRDs due to their genetic origin. Genetic testing can aid in diagnosis and, critically, it can determine if individuals have a specific mutation that may be treatable by specific gene therapies.
Genetic complexity of Inherited Retinal Diseases
A small number of IRDs are caused by mutations in one single gene. For example, Choroideremia (CHM), a progressive condition where vision loss primarily affects males, is caused by a mutation in a gene called CHM. Stargardt disease is caused by a mutation in a gene called ABCA4.
For most other IRDs, affected people may have the same symptoms and the same disease but each person could have mutations in different genes. This is because mutations in many different genes can all have the same end result. For example, RP can be caused by mutations in one of 84 different genes, while cone-rod dystrophy can be caused by mutations in one of 33 different genes. Mutations in 20 different genes can lead to macular dystrophies (MD) and another 15 different genes can be responsible for congenital stationary night blindness.
While mutations in different genes can result in the same disease, different changes in just one gene can sometimes result in different diseases in individuals. For example, different mutations in the GUCY2D gene can result in either cone-rod dystrophy or in LCA. Cone-rod dystrophy can be caused in some individuals by autosomal dominant (ad) variants of GUCY2D while autosomal recessive (ar) variants of the same gene can lead to LCA in other people.
In some instances, the severity of the disease can be affected by different combinations of different types of mutations. A person who has two non-functioning copies of ABC4A will have early-onset cone-rod dystrophy while another person with a combination of two severe and mild variants of ABC4A may have intermediate or late-onset Stargardt disease.
Autosomal recessive retinal dystrophies (arRDs) can be syndromic or non-syndromic. Non-syndromic vision loss is not associated with other signs and symptoms. In contrast, syndromic vision loss involves loss that also occurs with symptoms in other parts of the body. Different mutations in the USH2A gene can cause Usher syndrome type 2 or non-syndromic arRP.
Retina-IRD | Bringing Hope and Vision through Innovation and Research
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