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Exp Eye Res. 2012 Dec;105:21-6. doi: 10.1016/j.exer.2012.10.005. Epub 2012 Oct 16.
Previous studies in a mouse model of retinitis pigmentosa indicate that the GABAergic system in the retina may be overactive. GABA is known to act on GABA(C) receptors present on the axon terminals of bipolar cells to inhibit the release of excitatory neurotransmitter from these cells. The present study examined the effects of a GABA(C) receptor antagonist on the light-evoked responses of retinal ganglion cells (RGCs) in a rat model of retinitis pigmentosa. Extracellular recordings were made from RGCs in retinas isolated from P23H transgenic rats and non-dystrophic Sprague-Dawley (SD) rats. Spike activity of RGCs was measured in response to brief flashes of light over a range of light intensities. Intensity-response curves were evaluated prior to and during bath application of the GABA(C) receptor antagonist TPMPA. I found that TPMPA consistently increased the sensitivity of P23H rat RGCs to light flashes. For ON-center RGCs (n = 21), the average increase in light sensitivity was 0.63 log unit. For OFF-center RGCs (n = 6), the average increase was 0.38 log unit. TPMPA increased the maximum peak response of ON-center RGCs by 22% and OFF-center RGCs by 11%. However, the increase in maximum peak response of OFF-center RGCs was not statistically significant. TPMPA had no significant effect on the dynamic operating range of either ON-center or OFF-center RGCs. Nine ON-center SD rat RGCs were also tested. In contrast to what was observed for P23H rat RGCs, TPMPA decreased the sensitivity of these RGCs to light flashes, on average by 0.20 log unit. In conclusion, GABA(C) receptors may be novel targets for therapeutic interventions aimed at increasing light responsiveness in patients with retinitis pigmentosa or other diseases involving degeneration of photoreceptors.
先前在视网膜色素变性的小鼠模型中的研究表明，视网膜中的 GABA 能系统可能过度活跃。已知 GABA 作用于双极细胞轴突末梢上存在的 GABA(C)受体，抑制这些细胞释放兴奋性神经递质。本研究检查了 GABA(C)受体拮抗剂对视网膜色素变性大鼠模型中视网膜神经节细胞（RGC）的光诱发反应的影响。从 P23H 转基因大鼠和非营养不良型 Sprague-Dawley（SD）大鼠分离的视网膜中进行了 RGC 的细胞外记录。在一系列光强度下，通过短暂闪光来测量 RGC 的尖峰活动。在 GABA(C)受体拮抗剂 TPMPA 的浴施加之前和期间评估强度-反应曲线。我发现 TPMPA 一致增加了 P23H 大鼠 RGC 对光闪烁的敏感性。对于 ON 中心 RGC（n=21），光敏感性的平均增加为 0.63 log 单位。对于 OFF 中心 RGC（n=6），平均增加为 0.38 log 单位。TPMPA 使 ON 中心 RGC 的最大峰响应增加了 22%，OFF 中心 RGC 增加了 11%。然而，OFF 中心 RGC 的最大峰响应增加并不具有统计学意义。TPMPA 对 ON 或 OFF 中心 RGC 的动态工作范围没有显著影响。还测试了 9 个 ON 中心 SD 大鼠 RGC。与 P23H 大鼠 RGC 观察到的情况相反，TPMPA 平均使这些 RGC 对光闪烁的敏感性降低了 0.20 log 单位。总之，GABA(C)受体可能是治疗干预的新靶点，旨在增加视网膜色素变性或涉及光感受器变性的其他疾病患者对光的反应性。
