The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, 325027, China.
The Eye Hospital, School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, 325027, China.
Exp Eye Res. 2022 Jun;219:109068. doi: 10.1016/j.exer.2022.109068. Epub 2022 Apr 7.
In adult mammals, only minimal regeneration of the optic nerve (ON) is possible. Both the low levels of intrinsic regeneration ability of retinal ganglion cells (RGCs) and the inhibitory glial environment of ON contribute to it. To explore the influence of these two factors on the extent of axon regeneration, two ON injury models were established. A conventional optic nerve crush model (ONC) is considered a high-inhibitory environment. A long-range optic nerve injury model (LI) is considered a low-inhibitory environment. Zymosan (Zy) was used to regulate the intrinsic regeneration capability of RGCs: the injection of zymosan represented a high state; no injection represented a low state. In the low-inhibitory environment, zymosan (LI + Zy group) significantly increased both the number of regenerated axons and the number of surviving RGCs, however the Relative A/R (representing the proportion of regenerated RGCs) was similar to the LI group (no zymosan injection).Furthermore, in the highly-inhibitory environment, although zymosan (ONC + Zy group) significantly increased the number of regenerated axons and the number of surviving RGCs, the relative A/R was significantly lower than that in the low-inhibitory environment (LI or LI + Zy groups). The results suggest that the low inhibitory environment may be more important for optic nerve regeneration. Binary regression analysis also demonstrated the similar results. Also, there was a clear synergy between the two factors. These indicate that both low inhibitory environments and high regeneration capability can enhance the regeneration of ON. A low inhibitory environment is greater essential.
在成年哺乳动物中,视神经(ON)的再生能力非常有限。视网膜神经节细胞(RGCs)的内在再生能力低和 ON 的抑制性神经胶质环境都对此有影响。为了探究这两个因素对轴突再生程度的影响,建立了两种 ON 损伤模型。传统的视神经挤压模型(ONC)被认为是一种高抑制性环境,而长程视神经损伤模型(LI)被认为是一种低抑制性环境。几丁质酶(Zy)被用来调节 RGCs 的内在再生能力:Zy 的注射代表高状态,不注射则代表低状态。在低抑制性环境中,Zy(LI+Zy 组)显著增加了再生轴突的数量和存活的 RGCs 的数量,但是相对 A/R(代表再生 RGCs 的比例)与 LI 组(未注射 Zy)相似。此外,在高度抑制性环境中,尽管 Zy(ONC+Zy 组)显著增加了再生轴突的数量和存活的 RGCs 的数量,但相对 A/R 显著低于低抑制性环境(LI 或 LI+Zy 组)。结果表明,低抑制环境可能对 ON 再生更为重要。二元回归分析也得出了类似的结果。此外,这两个因素之间存在明显的协同作用。这些表明,低抑制环境和高再生能力都可以增强 ON 的再生,低抑制环境更为关键。