Isotretinoin (
13-cis retinoic acid) is frequently prescribed for severe
acne [Peck, G. L., Olsen, T. G., Yoder, F. W., Strauss, J. S., Downing, D. T., Pandya, M., Butkus, D. & Arnaud-Battandier, J. (1979) N. Engl. J. Med. 300, 329-333] but can impair night vision [Fraunfelder, F. T., LaBraico, J. M. & Meyer, S. M. (1985) Am. J. Ophthalmol. 100, 534-537] shortly after the beginning of
therapy [Shulman, S. R. (1989) Am. J. Public Health 79, 1565-1568]. As rod photoreceptors are responsible for night vision, we administered
isotretinoin to rats to learn whether
night blindness resulted from rod cell death or from rod functional impairment. High-dose
isotretinoin was given daily for 2 months and produced systemic toxicity, but this caused no histological loss of rod photoreceptors, and rod-driven electroretinogram amplitudes were normal after prolonged dark adaptation. Additional studies showed, however, that even a single dose of
isotretinoin slowed the recovery of rod signaling after exposure to an intense bleaching light, and that
rhodopsin regeneration was markedly slowed. When only a single dose was given, rod function recovered to normal within several days. Rods and cones both showed slow recovery from bleach after
isotretinoin in rats and in mice. HPLC analysis of ocular
retinoids after
isotretinoin and an intense bleach showed decreased levels of
rhodopsin chromophore, 11-cis
retinal, and the accumulation of the biosynthetic intermediates, 11-cis and
all-trans retinyl esters.
Isotretinoin was also found to protect rat photoreceptors from light-induced damage, suggesting that strategies of altering
retinoid cycling may have therapeutic implications for some forms of
retinal and
macular degeneration.