Visualizing an inherited retinal disease
These four images were taken through a person's enlarged, or dilated, pupil using different imaging methods. They show the back of the right eye, known as the retina.
This person has been diagnosed with X-linked retinoschisis (XLRS), also called juvenile retinoschisis. This inherited disease is caused by mutations in a gene called RS1, located on the X chromosome.
Women who have one copy of a mutated RS1 gene are called carriers. Carriers do not have symptoms of XLRS, but can pass the mutated RS1 gene to their children, with a 50 percent chance at each pregnancy. Because males have only one X chromosome, sons who inherit the mutated RS1 gene will have XLRS. Young boys who have XLRS usually show symptoms of poor central vision around school age, but vision problems can develop as early as infancy.
The RS1 gene produces a protein called retinoschisin, which is expressed in several layers of the retina. The term "schisis" comes from the Greek word for "splitting." In XLRS, the layers of the retina begin to split. The disease is usually diagnosed when a doctor notices cyst-like changes at the center of the retina, known as the fovea. These changes can decrease a male's central vision.
Image A is a color photograph of the retina that shows subtle, almost imperceptible, changes at the fovea. Image B is an autofluorescence photo taken using a specific wavelength of light (488 nanometers). Autofluorescence photos are used to view changes in the retinal pigment epithelial (RPE) layer just below the retina. XLRS does not directly affect the RPE, so this image looks nearly normal as well.
Changes in the fovea appear more noticeable as a "spoke-wheel" pattern in Image C, a "red-free" photograph where light is filtered to eliminate red colors and improve contrast. Retinal changes associated with the disease are most obvious in Image D, which was taken using optical coherence tomography (OCT). This technology provides a cross-sectional view of the retina, so the splitting of retinal layers is more evident.
NEI director Paul A. Sieving, M.D., Ph.D., is currently leading clinical and genetic studies of XLRS to better understand the relationship between the changes in the gene and the severity of retinal disease. Through these studies, NEI researchers are also working on the development of gene therapy treatment for XLRS.
Image courtesy of NEI staff clinician Catherine Cukras, M.D., and chief of the NEI Imaging Services Section Denise Cunningham, C.R.A., M.Ed.