Abstract
Purpose:
Palmitoylation is an important protein posttranslational modification. Increasing amount of evidence has shown that aberrant palmitoylation of targeted protein lead to the disruption of protein function and the development of disease. Well-known examples of palmitoylated protein in the eye include rhodpsin. However, not much is known about the enzymes and other target proteins in the eye. The purpose of the study is to examine the effect of protein palmitoylation inhibition on retinal function and the expression of protein palmitoyltransferase (PAT) genes in ocular tissues.
Methods:
Gene expression was compared by relative quantitative PCR alaysis. Protein palmitoylation was inhibited by intravitreal injection of 2-bromopalmitate (2-BP) in mouse or by adding 2-BP in cell culture medium. Light-induced retinal degeneration and electroretinogram were examined in mouse.
Results:
Out of 23 PAT genes, 15 were expressed in mouse cornea, lens, iris and retinal tissues. Some of the genes also showed significant changes during mouse eye development from embryonic day 10.5 to postnatal day 28. Twenty-four hours after the intravitreal injection of 3 μg 2-BP, the treated eye showed an averaged 25% reduction of the maximal responses of both a- and b-waves by ERG compared to solvent injected contralateral eye. White-light induced photoreceptor cell apoptosis was significantly less in the 2-BP injected eyes compared to solvent injected eyes, which was performed 48 hours after the injection. The addition of 50 mM 2-BP to cultured human retinal pigment epithelial cells (hRPE19) also induced broad changes of gene expression.
Conclusions:
Protein palmitoyltion play important roles in the maintenance of retinal function. Further studies are needed to identify specific PAT enzymes and their target proteins in ocluar tissues.