Once in a while an article appears that asks important questions, makes us think, and provokes change. In this issue of JAMA Ophthalmology, the article by Utz et al1 does just that.
We are in the midst of an unprecedented and exciting paradigm shift in ophthalmology and the visual sciences. We are deepening our understanding and appreciation of novel therapies for inherited retinal diseases (IRDs), diseases that we thought were untreatable only 20 years ago. However, to develop treatments for IRDs, we must understand the molecules of vision and we need to match the new IRD-associated genes to their phenotypes. Arguably, a second earlier and equally exciting paradigm shift was the elucidation of molecular players of the phototransduction cascade, the retinoid cycle, and intraflagellar transport. George Wald’s elucidation of the phototransduction cascade in 1965 led to the discovery of the first molecules of vision, which in turn led to the involvement of these mutant proteins in different IRD diseases, and subsequently the Nobel prize for Wald. The “Wald cycle,” or phototransduction cascade, starts the visual process by the biological conversion of photons of light, leading to the excitation of retinal molecules and electrical signaling from photoreceptors to bipolar cells followed by visual perception in the cerebral cortex.