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Clivia Erb, Sabrina Reinehr, Carsten Theiß, Burkhard Dick, Stephanie Christine Joachim

• \(\bf Introduction:\) 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 (\(\it HSP27\)). An intravitreal injection of \(\it HSP27\) leads to glaucoma-like damage in rats. We now aimed to investigate if aged mice are more prone to this damage than younger ones. \(\bf Methods:\) We intravitreally injected \(\it HSP27\) 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. \(\bf Results:\) 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 \(\it HSP27\) mice at both ages. Comparing aged and young \(\it HSP27\) mice, no differences in \(\it Rbpms\) and \(\it Pou4f1\) (RGCs) expression was detected, while the \(\it Tubb3\) expression (neuronal cells) was significantly upregulated in aged \(\it HSP27\) animals. Neither microglia/macrophages nor (resident) microglia counts revealed significant differences in \(\it HSP27\) mice at both ages. Nevertheless, increased relative \(\it Iba1\) and \(\it Tmem119\) expression was detected in young and aged \(\it HSP27\) mice. Aged \(\it HSP27\) mice displayed a significantly lower \(\it Iba1\) expression than young ones, whereas \(\it Cd68\) levels were upregulated. A larger \(\it GFAP+\) area and an upregulation of \(\it GFAP\) expression in \(\it HSP27\) animals of both ages indicated a macrogliosis. Also, elevated \(\it Il1b\) and \(\it Nos2\) expression levels were observed in young and aged \(\it HSP27\) mice. However, only \(\it Il1b\) levels were upregulated when comparing 7–8 months to 1–2 months old animals. A larger \(\it HSP25+\) area was seen in aged \(\it HSP27\) animals, while \(\it Hspb2\) expression levels were downregulated in both \(\it HSP27\) groups. The aged \(\it HSP27\) group displayed an upregulated \(\it Hspb2\) expression compared to young mice. Furthermore, a higher optic nerve degeneration score was noted in young and aged \(\it HSP27\) groups. \(\bf Discussion:\) These findings indicate that an intravitreal injection of \(\it HSP27\) led to \(\it RGC\) 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 \(\it HSP27\) in the development of glaucoma.