Inhibition of the visual cycle in vivo by 13 -cis retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy

• DOI: 10.1073/pnas.98.4.1835
• Publication Date: 2012-07-26T23:12:10Z
• Authors: Paul A. Sieving; Prem Chaudhry; Mineo Kondo; Matthew Provenzano; David Wu; Thomas J. Carlson; Ronald A. Bush; Debra A. Thompson
• Keywords: Isotretinoin; Electroretinography; Visual phototransduction

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