Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany.
Institute of Human Anatomy and Embryology, University Regensburg, Universitätsstraße 31, 93053 Regensburg, Germany.
Int J Mol Sci. 2021 Feb 17;22(4):1997. doi: 10.3390/ijms22041997.
To reveal the pathomechanisms of glaucoma, a common cause of blindness, suitable animal models are needed. As previously shown, retinal ganglion cell and optic nerve degeneration occur in βB1-CTGF mice. Here, we aimed to determine possible apoptotic mechanisms and degeneration of different retinal cells. Hence, retinae were processed for immunohistology ( = 5-9/group) and quantitative real-time PCR analysis ( = 5-7/group) in 5- and 10-week-old βB1-CTGF and wildtype controls. We noted significantly more cleaved caspase 3 cells in βB1-CTGF retinae at 5 ( = 0.005) and 10 weeks ( = 0.02), and a significant upregulation of and mRNA levels ( < 0.05). Furthermore, more terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) cells were detected in transgenic mice at 5 ( = 0.03) and 10 weeks ( = 0.02). Neurofilament H staining ( = 0.01) as well as ( = 0.02) and ( = 0.009) mRNA levels were significantly decreased at 10 weeks. GABAergic synapse intensity was lower at 5 weeks, while no alterations were noted at 10 weeks. The glutamatergic synapse intensity was decreased at 5 ( = 0.007) and 10 weeks ( = 0.01). No changes were observed for bipolar cells, photoreceptors, and macroglia. We conclude that apoptotic processes and synapse loss precede neuronal death in this model. This slow progression rate makes the βB1-CTGF mice a suitable model to study primary open-angle glaucoma.
为了揭示青光眼（一种常见的失明原因）的发病机制，需要合适的动物模型。如前所述，βB1-CTGF 小鼠的视网膜神经节细胞和视神经发生变性。在这里，我们旨在确定不同视网膜细胞的可能凋亡机制和变性。因此，对 5 至 10 周龄的βB1-CTGF 和野生型对照的视网膜进行免疫组织化学处理（每组= 5-9）和定量实时 PCR 分析（每组= 5-7）。我们注意到，在 5 周和 10 周时，βB1-CTGF 视网膜中的 cleaved caspase 3 细胞明显更多（= 0.005）和 10 周（= 0.02），并且 和 mRNA 水平显著上调（<0.05）。此外，在转基因小鼠中，更多的末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）细胞在 5 周（= 0.03）和 10 周（= 0.02）时被检测到。神经丝 H 染色（= 0.01）以及 （= 0.02）和 （= 0.009）mRNA 水平在 10 周时明显降低。5 周时 GABA 能突触强度降低，而 10 周时没有变化。谷氨酸能突触强度在 5 周（= 0.007）和 10 周（= 0.01）时降低。双极细胞、光感受器和大胶质细胞没有变化。我们得出结论，在该模型中，凋亡过程和突触丢失先于神经元死亡。这种缓慢的进展速度使βB1-CTGF 小鼠成为研究原发性开角型青光眼的合适模型。
