Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Belfast, United Kingdom.
Invest Ophthalmol Vis Sci. 2013 Oct 21;54(10):6798-805. doi: 10.1167/iovs.13-12362.
To investigate the role of γ-aminobutryic acid (GABA) in the regulation of arteriolar diameter in the rat retina.
The actions of GABA on arteriolar diameter were examined using ex vivo retinal whole-mount preparations and isolated vessel segments. In most experiments, arterioles were partially preconstricted with endothelin (Et)-1. The expression levels of GABAA and GABAB receptors on isolated rat retinal Müller cells were assessed by immunohistochemistry.
GABA (0.1-1 mM) evoked vasodilation or vasoconstriction of arterioles in whole-mount preparations. No such effects were observed with isolated vessel segments. In whole mount samples, the GABAA receptor agonist muscimol caused vasomotor responses in only a small proportion of vessels. In contrast, arteriolar responses to the GABAB receptor agonists baclofen and SKF97541 more closely resembled those observed with GABA. No responses were seen with the GABAC receptor agonist 5-methylimidazoleacetic acid. GABA-induced vasodilator responses were, for the most part, repeatable in the presence of the GABAA receptor antagonist bicuculline. These responses, however, were completely blocked in the presence of the GABAB receptor inhibitor 2-hydroxysaclofen. Strong immunolabeling for both GABAA and GABAB receptors was detected in isolated Müller cells. In the absence of Et-1-induced preconstriction, most vessels were unresponsive to bicuculline or 2-hydroxysaclofen.
GABA exerts complex effects on arteriolar diameter in the rat retina. These actions appear largely dependent upon the activation of GABAB receptors in the retinal neuropile, possibly those located on perivascular Müller cells. Despite these findings, endogenous GABA appears to contribute little to the regulation of basal arteriolar diameter in the rat retina.
研究γ-氨基丁酸（GABA）在调节大鼠视网膜小动脉直径中的作用。
使用离体视网膜全层培养物和分离的血管段来检测 GABA 对小动脉直径的作用。在大多数实验中，用内皮素（Et）-1 部分预收缩小动脉。通过免疫组织化学评估分离的大鼠视网膜 Müller 细胞上 GABAA 和 GABAB 受体的表达水平。
GABA（0.1-1 mM）在全层培养物中引起小动脉的血管舒张或收缩。在分离的血管段中没有观察到这种作用。在全层样本中，GABAA 受体激动剂 muscimol 仅引起一小部分血管的血管运动反应。相比之下，GABAB 受体激动剂 baclofen 和 SKF97541 引起的小动脉反应更类似于 GABA 观察到的反应。GABAC 受体激动剂 5-甲基咪唑乙酸没有反应。在 GABAA 受体拮抗剂 Bicuculline 存在的情况下，GABA 诱导的血管舒张反应在大多数情况下是可重复的。然而，这些反应在 GABAB 受体抑制剂 2-羟基-saclofen 存在的情况下完全被阻断。在分离的 Müller 细胞中检测到强烈的 GABAA 和 GABAB 受体免疫标记。在没有 Et-1 诱导的预收缩的情况下，大多数血管对 Bicuculline 或 2-羟基-saclofen 没有反应。
GABA 对大鼠视网膜小动脉直径产生复杂的影响。这些作用似乎主要依赖于视网膜神经丛中 GABAB 受体的激活，可能位于血管周围的 Müller 细胞上。尽管有这些发现，但内源性 GABA 似乎对大鼠视网膜基础小动脉直径的调节贡献不大。
