inhibiting the formation of 11-cis-retinal. Stored all-trans-retinyl palmitate is simultaneously hydrolysed and isomerised to 11-cis-retinol by RPE-65. The 11-cis-retinol is oxidized to 11-cis retinal and transported to photoreceptor cells where it binds to opsin to form rhodopsin. Emixustat hydrochloride binds to RPE-65 and prevents the isomerohydrolase reaction. Without 11-cis-retinal, the rod photoreceptor cells no longer produce all-trans-retinol and production of A2E is halted. The isomerisation of all-trans-retinol to 11-cis-retinol also plays a key role in the pathogenesis of diabetic macular edema (DME), but by a different outcome of the same mechanism. One of the consequences of diabetes is damage to blood vessels; damaged vessels are less able to carry oxygen, thus inhibiting one of the most important biological processes within the eye. Normal retinal cells require a very large amount of oxygen. When insufficient oxygen is available, vascular remodelling occurs and poorly remodelled blood vessels leak, causing edema. The conversion of all-trans-retinol to 11-cis-retinal is a very oxygen intensive process. By blocking the isomerisation of retinol, emixustat hydrochloride may decrease the oxygen demand of the retina and therefore liberate large amounts of oxygen for other processes. In a completed Phase 1a study, the drug was "well tolerated" by male and female human participants, and demonstrated dose-dependent modulation of electroretinogram (ERG) signals. A Phase II study, completed in 2015, produced a dose dependent, reversible effect on rod function consistent with emixustat's planned mechanism of action. See also Visual phototransduction Retinol isomerase References Further reading External links Associated patents, ianscottmolecular.com Experimental drugs Cyclohexyl compounds Phenol ethers