The axons of retinal ganglion cells (RGCs) in adult mammals fail to regenerate after injury. It has been suggested that some extrinsic factors, such as neural activity, may promote the regeneration process. The present study tested the hypothesis that environmental stress such as slightly elevated osmolarity and temperature can enhance neural activity and thus promote axon regeneration of RGCs in postnatal mice. Retinal explants from P9-11 mice were cultured for 5 days to study the capacity of RGC neurite outgrowth. The neural activity of retinal explants in these two stress conditions was examined using the multi-electrode array. We found that RGC neurite outgrowth from P9-P11 mouse explants was significantly enhanced when the concentration of the culture medium was increased by 1.25 fold, but not when increased by 1.5 fold. Similarly, retinal explants from P9-P11 mice grew longer neurites when the overall temperature was increased from 35 °C to 38 °C, 40 °C or 42 °C for one hour each day, but not when they were kept at 40 °C or 42 °C constantly for five days. We further showed that there was increased neural activity during these two mild stress conditions. It was found that short-term 42 °C heat stress increased the expression of heat shock proteins 27 and 70 in postnatal retinas and they were RGC neural activity dependent. The present study thus provides insights into the cellular mechanism of retinal axon regeneration under the mild stress conditions.

成年哺乳动物的视网膜神经节细胞 (RGC) 的轴突在受伤后无法再生。有人提出一些外在因素，如神经活动，可能会促进再生过程。本研究检验了这样一个假设，即环境压力（如略升高的渗透压和温度）可以增强神经活动，从而促进出生后小鼠 RGC 的轴突再生。将来自 P9-11 小鼠的视网膜外植体培养 5 天以研究 RGC 神经突生长的能力。使用多电极阵列检查了这两种压力条件下视网膜外植体的神经活动。我们发现当培养基浓度增加 1.25 倍时，来自 P9-P11 小鼠外植体的 RGC 神经突生长显着增强，但当增加 1.5 倍时则没有。相似地，当总体温度从 35 °C 增加到 38 °C、40 °C 或 42 °C 每天一小时时，来自 P9-P11 小鼠的视网膜外植体的神经突长出更长的时间，但当它们保持在 40 °C 或 42 °C 时则不然°C 连续五天。我们进一步表明，在这两种轻度压力条件下，神经活动增加。发现短期 42°C 热应激增加了出生后视网膜中热休克蛋白 27 和 70 的表达，并且它们依赖于 RGC 神经活动。因此，本研究提供了对轻度压力条件下视网膜轴突再生的细胞机制的见解。我们进一步表明，在这两种温和的压力条件下，神经活动增加。发现短期 42°C 热应激增加了出生后视网膜中热休克蛋白 27 和 70 的表达，并且它们依赖于 RGC 神经活动。因此，本研究提供了对轻度压力条件下视网膜轴突再生的细胞机制的见解。我们进一步表明，在这两种轻度压力条件下，神经活动增加。发现短期 42°C 热应激增加了出生后视网膜中热休克蛋白 27 和 70 的表达，并且它们依赖于 RGC 神经活动。因此，本研究提供了对轻度压力条件下视网膜轴突再生的细胞机制的见解。