Centro Interdisciplinario de Neurociencia de Valparaíso (CINV), Universidad de Valparaíso, Valparaíso, Chile.
Programa de Doctorado en Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
Invest Ophthalmol Vis Sci. 2024 Jan 2;65(1):46. doi: 10.1167/iovs.65.1.46.
Members of the secretin/glucagon family have diverse roles in retinal physiological and pathological conditions. Out of them, glucagon has been associated with eye growth regulation and image defocus signaling in the eye, both processes central in myopia induction. On the other hand, dopamine is perhaps the most studied molecule in myopia and has been proposed as fundamental in myopia pathogenesis. However, glucagonergic activity in the mammalian retina and its possible link with dopaminergic signaling remain unknown.
To corroborate whether glucagon and dopamine participate together in the modulation of synaptic activity in the retina, inhibitory post-synaptic currents were measured in rod bipolar cells from retinal slices of wild type and negative lens-exposed mice, using whole cell patch-clamp recordings and selective pharmacology.
Glucagon produced an increase of inhibitory post-synaptic current frequency in rod bipolar cells, which was also dependent on dopaminergic activity, as it was abolished by dopamine type 1 receptor antagonism and under scotopic conditions. The effect was also abolished after 3-week negative lens-exposure but could be recovered using dopamine type 1 receptor agonism.
Altogether, these results support a possible neuromodulatory role of glucagon in the retina of mammals as part of a dopaminergic activity-dependent synaptic pathway that is affected under myopia-inducing conditions.
分泌素/胰高血糖素家族的成员在视网膜的生理和病理状态中具有多种作用。其中,胰高血糖素与眼睛的生长调节和图像离焦信号有关,这两个过程都是近视诱导的核心。另一方面,多巴胺也许是近视研究最多的分子,并被提出是近视发病机制的基础。然而,哺乳动物视网膜中的胰高血糖素能活性及其与多巴胺能信号传递的可能联系尚不清楚。
为了证实胰高血糖素和多巴胺是否共同参与调节视网膜中的突触活动,我们使用全细胞膜片钳记录和选择性药理学方法,在来自野生型和负透镜暴露的小鼠视网膜切片中的杆状双极细胞中测量抑制性突触后电流。
胰高血糖素可增加杆状双极细胞的抑制性突触后电流频率,这也依赖于多巴胺能活性,因为它被多巴胺 1 型受体拮抗剂和在暗视条件下所阻断。在 3 周的负透镜暴露后,这种作用也被消除,但可以通过多巴胺 1 型受体激动剂恢复。
总之,这些结果支持胰高血糖素在哺乳动物视网膜中作为多巴胺能活性依赖的突触途径的一部分发挥可能的神经调节作用,该途径在近视诱导条件下受到影响。