Photoreceptor-specific degeneration caused by tunicamycin

The antibiotic tunicamycin inhibits the biosynthesis of N-acetyl-glucosaminylpyrophosphoryl polyisoprenol^1-3, a key intermediate in the formation of the asparagine-linked oligosaccharides of glycoproteins⁴. The effects of tunicamycin have been studied in various biological systems⁵, primarily with the aim of elucidating the role of the carbohydrate moieties in the cellular function of glycoproteins⁶. Rhodopsin, the visual pigment of retinal rod photoreceptor cells, is a membrane glycoprotein which consists of a single polypeptide chain (opsin) to which a chromophoric prosthetic group (II-cis-retinaldehyde) and two asparagine-linked oligosaccharide chains are covalently attached⁷. The glycosylation of opsin can be blocked with tunicamycin in vitro in conditions where polypeptide synthesis is only slightly decreased^8,9. We have reported⁹ that tunicamycin can disrupt the normal assembly of rod outer segment membranes in vitro without significantly inhibiting the biosynthesis or intracellular transport of opsin. Here we report that intraocular injection of tunicamycin produces a photoreceptor-specific degeneration characterized by (1) progressive shortening of rod outer segment, (2) decreased electroretinogram amplitudes, (3) cessation of rod outer segment membrane assembly, and (4) eventual photoreceptor cell death.