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Frontiers in Cellular Neuroscience 2023Age-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...
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 (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.
METHODS
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.
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 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.
DISCUSSION
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.
PubMed: 37744880
DOI: 10.3389/fncel.2023.1257297 -
International Journal of Molecular... Mar 2024Increased intraocular pressure (IOP) is the most important risk factor for glaucoma. The role of IOP fluctuation, independently from elevated IOP, has not yet been...
Increased intraocular pressure (IOP) is the most important risk factor for glaucoma. The role of IOP fluctuation, independently from elevated IOP, has not yet been confirmed in glaucoma. We investigated the effects of IOP fluctuation itself on retinal neurodegeneration. Male rats were treated with IOP-lowering eyedrops (brinzolamide and latanoprost) on Mondays and Thursdays (in the irregular instillation group) or daily (in the regular instillation group), and saline was administered daily in the normal control group for 8 weeks. The IOP standard deviation was higher in the irregular instillation group than the regular instillation group or the control group. The degree of oxidative stress, which was analyzed by labeling superoxide, oxidative DNA damage, and nitrotyrosine, was increased in the irregular instillation group. Macroglial activation, expressed by glial fibrillary acidic protein in the optic nerve head and retina, was observed with the irregular instillation of IOP-lowering eyedrops. Microglial activation, as indicated by Iba-1, and the expression of TNF-α did not show a significant difference between the irregular instillation and control groups. Expression of cleaved caspase-3 was upregulated and the number of retinal ganglion cells (RGCs) was decreased in the irregular instillation group. Our findings indicate that IOP fluctuations could be induced by irregular instillation of IOP-lowering eyedrops and this could lead to the degeneration of RGCs, probably through increased oxidative stress and macrogliosis.
Topics: Male; Animals; Rats; Intraocular Pressure; Retina; Glaucoma; Retinal Ganglion Cells; Ophthalmic Solutions
PubMed: 38612500
DOI: 10.3390/ijms25073689