Erb Clivia, Reinehr Sabrina, Theiss Carsten, Dick H Burkhard, Joachim Stephanie C
Experimental Eye Research Institute, University Eye Hospital, Ruhr-University Bochum, Bochum, Germany.
Institute of Anatomy, Department of Cytology, Ruhr-University Bochum, Bochum, Germany.
Front Cell Neurosci. 2023 Sep 7;17:1257297. doi: 10.3389/fncel.2023.1257297. eCollection 2023.
Age-related diseases such as glaucoma, a leading cause of blindness, are having an upward trend due to an aging society. In glaucoma, some patients display altered antibody profiles and increased antibody titers, for example against heat shock protein 27 (HSP27). An intravitreal injection of HSP27 leads to glaucoma-like damage in rats. We now aimed to investigate if aged mice are more prone to this damage than younger ones.
We intravitreally injected HSP27 into young (1-2 months) and aged (7-8 months) mice to compare glaucomatous damage. Respective age-matched controls received PBS. Not injected eyes served as naive controls.
Optical coherence tomography 4 weeks after injection showed no changes in retinal thickness in all groups at both ages. Cell counts and RT-qPCR revealed a significant reduction in RGC numbers in HSP27 mice at both ages. Comparing aged and young HSP27 mice, no differences in and (RGCs) expression was detected, while the expression (neuronal cells) was significantly upregulated in aged HSP27 animals. Neither microglia/macrophages nor (resident) microglia counts revealed significant differences in HSP27 mice at both ages. Nevertheless, increased relative and expression was detected in young and aged HSP27 mice. Aged HSP27 mice displayed a significantly lower expression than young ones, whereas levels were upregulated. A larger GFAP area and an upregulation of expression in HSP27 animals of both ages indicated a macrogliosis. Also, elevated and expression levels were observed in young and aged HSP27 mice. However, only levels were upregulated when comparing 7-8 months to 1-2 months old animals. A larger HSP25 area was seen in aged HSP27 animals, while expression levels were downregulated in both HSP27 groups. The aged HSP27 group displayed an upregulated expression compared to young mice. Furthermore, a higher optic nerve degeneration score was noted in young and aged HSP27 groups.
These findings indicate that an intravitreal injection of HSP27 led to RGC loss accompanied by inflammation. Age-dependent effects (7-8 months vs. 1-2 months) were not very prominent. The results suggest a potential role of extracellular HSP27 in the development of glaucoma.
与年龄相关的疾病，如青光眼（失明的主要原因），由于社会老龄化呈上升趋势。在青光眼中，一些患者表现出抗体谱改变和抗体滴度增加，例如针对热休克蛋白27（HSP27）的抗体。玻璃体内注射HSP27会导致大鼠出现青光眼样损伤。我们现在旨在研究老年小鼠是否比年轻小鼠更容易受到这种损伤。
我们将HSP27玻璃体内注射到年轻（1 - 2个月）和老年（7 - 8个月）小鼠体内，以比较青光眼损伤情况。各自年龄匹配的对照组接受PBS。未注射的眼睛作为未处理对照。
注射后4周的光学相干断层扫描显示，两个年龄组的所有组视网膜厚度均无变化。细胞计数和RT-qPCR显示，两个年龄组的HSP27小鼠视网膜神经节细胞（RGC）数量均显著减少。比较老年和年轻的HSP27小鼠，未检测到RGC数量和表达的差异，而老年HSP27动物中神经元细胞的表达显著上调。在两个年龄组的HSP27小鼠中，小胶质细胞/巨噬细胞和（驻留）小胶质细胞计数均未显示出显著差异。然而，在年轻和老年HSP27小鼠中检测到相对表达增加。老年HSP27小鼠的表达明显低于年轻小鼠，而水平上调。两个年龄组的HSP27动物中更大的胶质纤维酸性蛋白（GFAP）面积和表达上调表明存在大胶质细胞增生。此外，在年轻和老年HSP27小鼠中观察到和表达水平升高。然而，将7 - 8个月大的动物与1 - 2个月大的动物比较时，只有水平上调。在老年HSP27动物中观察到更大的HSP25面积，而在两个HSP27组中表达水平均下调。与年轻小鼠相比，老年HSP27组的表达上调。此外，在年轻和老年HSP27组中观察到更高的视神经变性评分。
这些发现表明，玻璃体内注射HSP27会导致RGC丢失并伴有炎症。年龄依赖性效应（7 - 8个月与1 - 2个月）不太明显。结果表明细胞外HSP27在青光眼发展中可能起作用。
