Revisiting retinal and macular degeneration in the genomics era

Retinal and macular degeneration constitute a prominent cause of untreatable vision loss globally. The development of efficacious therapies is impeded by extensive clinical and genetic heterogeneity, poor phenotype-genotype correlation and lack of appropriate disease models. Pioneering advances in next-generation sequencing together with computational methods, human model systems and genetic manipulation technologies have begun to unravel causal genes and variants as well as gene interaction networks. Photoreceptor dysfunction or death represents the end point for both Mendelian and complex traits affecting the retina or its specialized central region, the macula. Here we review the genetic and genomic bases of retinal and macular degeneration and how recent advances are informing therapies to slow the loss of or restore vision.