RDH8 Inhibitors

RDH8, or Retinol Dehydrogenase 8, plays a vital role in the visual cycle by facilitating the conversion of all-trans-retinal to all-trans-retinol. This conversion ensures the proper function of the eye, especially under high light conditions, and assists in the prevention of toxic accumulation of all-trans-retinal in the retina. Given its fundamental role in the visual cycle, the activity and expression of RDH8 can be subject to modulation by specific chemical agents. These agents that can hinder the activity or expression of RDH8 are categorized as RDH8 inhibitors.

The inhibitors of RDH8 encompass a diverse array of chemical compounds. For instance, retinoic acid, a metabolite of retinol, might operate through a feedback inhibition mechanism. The rationale here is that an abundance of downstream metabolites, like retinoic acid, might signal the cell to curtail the production processes leading to them, thus inhibiting enzymes involved in their synthesis, including RDH8. Other compounds such as hydroquinone can interfere with the redox state of the cell, which might impinge on the activity of redox-sensitive enzymes like RDH8. Flavonoids such as quercetin, naringenin, and fisetin, known for their enzyme-modulatory properties, could bind to RDH8 at its active or allosteric sites, altering its enzymatic efficiency. On the other hand, compounds like tretinoin, given their integral role in retinoid metabolism, might interact with the cellular regulatory pathways of RDH8. These RDH8 inhibitors, through their distinct chemical structures and mechanisms, highlight the intricate network of interactions and regulations surrounding this pivotal enzyme in the visual cycle.