Antiandrogenic effect of isotretinoin: is the retina involved in mechanism of action?

Isotretinoin (13-cis retinoic acid) has been the most effective available drug for severe acne vulgaris. Isotretinoin inhibits proliferation of sebocytes and can also reduce lipid synthesis, but its antiandrogenic effect remains uncertain. Decreased dark adaptation is one of the commonest ophthalmological adverse events of isotretinoin, which could be transient and permanent as well. Isotretinoin causes loss of night vision by slowing rhodopsin regeneration and chromophore recycling by the inhibition of 11-cis retinol dehydrogenase. The primary photoreceptors of the circadian pacemaker are the melanopsin containing intrinsically photosensitive retinal ganglion cells (ipRGC). Since the photochemistry of melanopsin is very similar to other opsin photopigments, and it is known that melanopsin uses the same retinaldehyde chromophore, it is hypothesized here that isotretinoin may exert inhibitory effect on chromophore regeneration in ipRGCs similar to what is seen in rod and cone cells, thus enabling to alter circadian and circannual rhythms. Mechanism of action of isotretinoin may involve neuroendocrine-reproductive axis in its antiandrogenic effect, and melatonin may mediate this action.