Inherited retinal diseases (IRDs) include a collection of heterogeneous processes characterized by variable dysfunction of rods and cones, the photoreceptors of vision. Genes that are mutated in IRDs encode proteins that lead to dysfunction through multiple mechanisms, often interfering with normal function of the visual cycle. The visual cycle is a biochemical loop which regenerates necessary visual pigments – chromophores – that are required for the transduction of light stimulation into an electrical signal. It is the action potential so generated by retinal ganglion cells that initiates the process of central neural processing which unfolds into vision. Key enzymes in this cycle are retinal pigment epithelium (RPE)-specific protein 65 kDa (RPE65) and lecithin:retinol acetyltransferase (LRAT), which are encoded by the RPE65 and LRAT genes, respectively.
In the normal functioning visual cycle, vitamin A from serum is taken up by retinal pigment epithelium (RPE) cells to generate a crucial metabolite, 11-cis-retinal. Photoreceptors use 11–retinal to generate the photopigment rhodopsin by complexing with the protein opsin. Rhodopsin absorbs light striking photoreceptors, and initiates processing essential for vision.