Abstract
Abstract: :
Purpose: Retinal mRNA levels for the transcription factor ZENK, glucagon and the glucagon receptor are controlled by the state of focus of the retinal image. Recent studies revealed strong co–regulation of these genes, with expression levels changing in both spectacle lens–treated eyes and their fellow untreated eyes although only the treated eyes show altered growth. The mechanism underlying this co–regulation of gene expression is not known. Since the optic nerve could subserve a neural coupling mechanism, we examined the effects of cutting the optic nerve (ONS) of lens–treated eyes on gene expressions in both eyes. Methods: Chicks (n=18) underwent unilateral ONS one day after hatching. Ten days later, –10 D spectacle lenses were attached to some of the ONS eyes for 30 min (n=6) or 2 hours (n=7); other ONS eyes were left without lenses (n=5). ONS–birds were compared to chicks that did not undergo ONS but were otherwise treated similarly (n=5, n=6, n=6, respectively). Real–time RT–PCR was applied to RNA isolated from retinal tissue to measure transcriptional changes of ZENK, glucagon and glucagon receptor. Results: In line with previous results, a significant reduction in ZENK expression to 33% of the control (no lens) level was observed after two hours of negative lens wear (p = 0.0065). ZENK expression was also reduced in the fellow eyes of these lens–treated eyes, although only to 59%. The results were similar even when lens–treated eyes first underwent ONS (42% and 59%, respectively). Glucagon and glucagon receptor mRNA levels were not affected by the lens treatment, although both levels were elevated in ONS–eyes relative to their fellow eyes (p=0.0018 and p=0.0136, respectively). Conclusions: The co–regulation of retinal gene expression in response to defocus manipulations does not seem to require an intact optic nerve. The contralateral effect therefore cannot be explained by neural coupling. It is possible that humoral factors are responsible for the signal transduction in the contralateral (fellow) eyes.
Keywords: myopia • retina • gene/expression