Genetics update of macular diseases

Abstract

Significant progress has been made in recent years in the discovery of genes causing early-onset inherited macular diseases [54]. The identification of these genes and their disease-causing mutations can aid in the diagnosis of patients who are genetically affected but have not yet developed the clinical phenotype. By understanding the primary defect in the pathophysiology of these diseases, treatment can be directed to the earlier stages in disease pathways, perhaps delaying or preventing the onset of vision loss. Furthermore, the disease gene could be replaced with a normal copy, allowing expression of the normal protein and potentially avoiding the disease phenotype altogether. Much work remains to elucidate the biologic mechanisms by which these genetic mutations result in disease phenotypes. Understanding the interaction of the disease genes with genetic background resulting in a normal phenotype, as in Best disease, or a completely different clinical entity, as in RDS-associated pattern dystrophy, could lead to useful therapies for these and other macular diseases. Animal models created by removing the normal genes, similar to what was performed with ABCA4, can assist in the development of therapeutic interventions. Further insight into the biochemical processes that cause macular dystrophies, including AMD, will contribute to our ability to develop treatments that will become increasingly vital in the years to come.