Visionary genomics

We have come a very long way since the days of John Dalton and his 1794 paper on the origins of colour blindness, a condition he shared with his brother [1]. Investigators from the vision research community have worked out the major pathways of how visual information is received, processed and transmitted to the brain, and how specialised tissues such as the cornea and lens work together to focus light on the retina and filter out harmful ultraviolet light. Molecular pathways responsible for the expression and accumulation of crystallins, the specialised proteins that make up 35 per cent of the wet weight of the ocular lens, have been discovered and studied in great detail. Genes for virtually all components of the phototransduction cascade have been identified and studied to define a host of molecular defects associated with anomalous perception of the visual world.Now that we have a comprehensive understanding of the genes responsible for the organisation and functional integration of the visual system, it is reasonable to consider the challenges posed by major heritable vision diseases that either are not treatable or for which current therapies cannot meet the global burden of disease. We can ponder whether the emergence of next-generation genome technologies will lead us closer to discovering new therapeutic strategies and achieving improved care of patients with vision disorders. Two major blinding conditions, age-related macular degeneration (AMD) and glaucoma, can serve as useful examples to highlight how far we have come, and how far we have yet to go, in our understanding of genetic influence on disease pathogenesis.AMD is the leading cause of blindness in people aged over 60 years in North America. Many commonalities have been associated with the complex manifestation of AMD, including accumulation of excess oxidised lipoproteins in the form of drusen; atrophy of the retinal pigment epithelium; formation of new blood vessels in the choroid; and environmen