Feldkaemper Marita P, Schaeffel Frank
University Eye Hospital Tuebingen, Section of Neurobiology of the Eye, Calwerstrasse 7/1. 72076 Tuebingen, Germany.
Vis Neurosci. 2002 Nov-Dec;19(6):755-66. doi: 10.1017/s0952523802196064.
Eye growth and refraction are regulated by visual processing in the retina. Until now, the messengers released by the retina to induce these changes are largely unknown. Previously, it was found that glucagon amacrine cells respond to defocus in the retinal image and even to its sign. The expression of the immediate-early gene product ZENK increased in this cell population in eyes wearing plus lenses and decreased in minus lens-treated chicks. Moreover, it was shown that the amount of retinal glucagon mRNA increased during treatment with positive lenses. Therefore, it seems likely that these cells contribute to the visual regulation of ocular growth and that glucagon may act as a stop signal for eye growth. The purpose of the present study was to accumulate further evidence for a role of glucagon in the visual control of eye growth. Chicks were treated with plus and minus lenses after injection of different amounts of the glucagon antagonist des-His1-Glu1-glucagon-amide or the agonist Lys17,18,Glu21-glucagon, respectively. Refractive development and eye growth were recorded by automated infrared photorefraction and A-scan ultrasound, respectively. The glucagon antagonist inhibited hyperopia development, albeit only in a narrow concentration range, and at most by 50%, but not myopia development. In contrast, the agonist inhibited myopia development in a dose-dependent fashion. At high concentrations, it also prevented hyperopia development. The amount of glucagon peptide in the retinae and choroids of lens-treated chicks and its diurnal variation was measured by using a radio-immunoassay. Retinal glucagon content decreased after minus lens treatment and choroidal glucagon content increased after plus lens treatment. No diurnal variation in the retinal amount of glucagon was detected. In addition, using an optokinetic nystagmus paradigm, the effect of glucagon and the antagonist des-His1-Glu9-glucagon-amide on suprathreshold contrast sensitivity was studied. Glucagon reduced contrast sensitivity (which might be linked to a signal for growth inhibition) whereas the antagonist des-His1-Glu9-glucagon-amide increased contrast sensitivity. The results of the study are in line with the hypothesis that glucagon plays a role in the visual control of eye growth in the chick.
眼睛的生长和屈光由视网膜中的视觉处理过程调节。到目前为止,视网膜释放以诱导这些变化的信使在很大程度上尚不清楚。此前,人们发现胰高血糖素无长突细胞对视网膜图像中的散焦甚至其符号有反应。在佩戴正透镜的雏鸡中,这一细胞群体中即早基因产物ZENK的表达增加,而在佩戴负透镜处理的雏鸡中则减少。此外,研究表明在用正透镜处理期间视网膜胰高血糖素mRNA的量增加。因此,这些细胞似乎有助于眼睛生长的视觉调节,并且胰高血糖素可能作为眼睛生长的停止信号。本研究的目的是积累更多证据证明胰高血糖素在眼睛生长的视觉控制中的作用。分别给雏鸡注射不同量的胰高血糖素拮抗剂去组氨酸1-谷氨酸1-胰高血糖素酰胺或激动剂赖氨酸17,18,谷氨酸21-胰高血糖素后,再用正透镜和负透镜进行处理。分别通过自动红外验光和A超超声记录屈光发育和眼睛生长情况。胰高血糖素拮抗剂抑制了远视的发展,尽管仅在狭窄的浓度范围内,且最多抑制50%,但对近视发展没有抑制作用。相反,激动剂以剂量依赖性方式抑制近视发展。在高浓度时,它也阻止了远视的发展。使用放射免疫分析法测量了经透镜处理的雏鸡视网膜和脉络膜中胰高血糖素肽的量及其昼夜变化。负透镜处理后视网膜胰高血糖素含量降低,正透镜处理后脉络膜胰高血糖素含量增加。未检测到视网膜中胰高血糖素量的昼夜变化。此外,使用视动性眼球震颤范式,研究了胰高血糖素和拮抗剂去组氨酸1-谷氨酸9-胰高血糖素酰胺对阈上对比敏感度的影响。胰高血糖素降低了对比敏感度(这可能与生长抑制信号有关),而拮抗剂去组氨酸1-谷氨酸9-胰高血糖素酰胺增加了对比敏感度。该研究结果与胰高血糖素在雏鸡眼睛生长的视觉控制中起作用这一假设一致。