How does the retina work?
At the back of the eye, the retina is composed of different cell layers, which detect the light. In the retina, the light is transformed into electric signals and these signals are transmitted to the brain through the optic nerve.
The light-sensitive retinal cells are called the photoreceptors. There are two types of photoreceptors: rods and cones. Rods are responsible for vision in dim light (scotopic vision) and for peripheral vision. They are the most abundant type of photoreceptors in the retina. Cones are responsible for central vision, colour vision and in higher light levels (photopic vision). Cones are important for precise vision (read, watch television…), while rods are important to see contrast and movement. Less present than rods in the retina, cone photoreceptors are restricted to the fovea.
Retinitis Pigmentosa and Leber Congenital Amaurosis
Retinitis pigmentosa (RP) is the name given to a group of progressive inherited retinal dystrophies. Patients with retinitis pigmentosa experience first night blindness, followed by a loss of peripheral vision (tunnel vision), and then loss of central vision. The onset and the severity of retinitis pigmentosa vary according to the mutated gene. Retinitis pigmentosa affects 1 in ~4000 individuals.
Leber congenital amaurosis (LCA) is a rare inherited retinal dystrophy characterised by severe loss of vision from birth. It can be seen as the early-onset form of Retinitis Pigmentosa (RP). Patients with LCA experience night blindness, loss of peripheral vision (tunnel vision) and eventually loss of central vision. Some patients have crossed eyes (strabismus), shaking eyes (nystagmus), light-sensitivity (photophobia), thin and cone-shaped cornea (keratoconus), hypermetropia and their pupils have delayed light reflex. Moreover, some patients poke, press or rub their eyes. LCA affects about 1 in 80,000 people around the world and is the most common form of inherited sight loss in children.
RDH12 Inherited Retinal Dystrophy
Over 80 genes have been associated with RP and over 25 with LCA. Genetic testing is needed to identify the disease-causing change(s) (mutation(s)) associated with RP or LCA.
One of these genes is RDH12. RDH12 gene codes retinal dehydrogenase 12 or the RDH12 protein. In the retina, RDH12 recycles molecules, called retinols, important for light detection. RDH12 plays a critical role in reducing oxidative stress, produced by the light. Excess of oxidative stress affects photoreceptor functions and survival.
Mutations in RDH12 are associated with an autosomal recessive early-onset LCA, which represents 10% of LCA cases. In rare cases, RDH12 mutations lead to autosomal dominant late-onset retinitis pigmentosa. Patients with early-onset LCA experience the first symptoms within the 2 first years of life; while patients with late-onset retinitis pigmentosa experience the first symptoms in their second decade of life.
Patients with early-onset RDH12 LCA experience night blindness, restriction of visual field and progression to full blindness generally by their late teens/ early twenties. No child experiences the same RDH12 disease progression, making the diagnosis particularly difficult and the molecular diagnosis essential.
Today, there is no current treatment for RDH12-related diseases. Over the world, researchers study these diseases to understand disease-causing mechanisms and identify potential treatments. Eyes on the Future and the global RDH12 Alliance are directly supporting researchers to advance our knowledge of RDH12 towards potential treatments.