Generating a Zebrafish Model to Study AMD
This project will address if the loss of retinal pigmented epithelial (RPE) cells is the primary or secondary cause of cone cell loss in macular degeneration. Using zebrafish, which possesses the ability to regenerate photoreceptor cells in the eye, we will also examine if the damaged RPE cells can be regenerated and the subsequent consequences on cone photoreceptor cell regeneration.
In age‐related macular degeneration (AMD), the retinal pigment epithelium (RPE) cells, which are located behind the retina and are essential to keep the light‐detecting rod and cone photoreceptor cells alive, are damaged and die. However, it is unclear if the RPE cell death is the primary cause of AMD or a secondary effect. To address this question, Dr. David Hyde and collaborators will generate a zebrafish model of AMD, where a number of the retinal RPE cells die. They will then test whether the death of RPE cells is sufficient to cause two hallmarks of advanced AMD—the death of the adjacent photoreceptor cells and the appearance of tears in the blood‐retina barrier (called Bruch's membrane). Since zebrafish have a natural ability to regenerate a number of body parts, including retinal neurons, these researchers will also determine if the RPE cell layer can spontaneously repair itself and, if so, determine the origin of these new RPE cells. Studying how the zebrafish eye can repair its RPE and retina will give clues for future RPE cell replacement therapies for people with AMD.