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T H Khanh Vu, Kin-Sang Cho, Martine Jager, Dong Chen; The Role Of Ageing In Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5648. doi: https://doi.org/.
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A number of degenerative retinal diseases are age-related, including glaucoma. It is believed that basic differences exist in the immunological microenvironment of eyes from young and old individuals. In addition, emerging studies report that the immune system plays an important role in glaucoma. Therefore, we studied whether old mice, presumably harboring a low level of age-related ocular para-inflammation, were more sensitive to neurodegeneration after IOP elevation than young mice.
Elevation of IOP was induced by anterior chamber (AC) injection of microbeads (MB), while controls received an injection of phosphate buffered saline (PBS).Twelve weeks-old C57BL/6J mice injected with MB or PBS were compared with 12 months-old mice injected with MB or PBS. IOP was measured on day 2, 7, 10, 14, 17, 21, and 24. At 4 weeks post-injection, all mice were sacrificed and retinal ganglion cell (RGC) quantification was performed by βIII-tubulin immunofluorescence staining in retinal sections. In addition, ocular immune responses were evaluated by detecting anti-Hsp responding T cells with an IFN-γ enzyme-linked immunosorbent spot and fluorescence-activated cell sorting assay.
A single injection of MB in the AC resulted in a significant IOP elevation that lasted approximately 3 weeks in both young and old mice. Control mice with PBS injection showed no significant change in IOP. Remarkably, aged mice exhibited an increased loss of RGCs as compared to young mice after MB injection, while in controls; no significant difference was noted in the number of RGCs between young and old mice. Higher levels of Hsp27-specific CD4+ T cells were seen subsequent to MB injection in both young and aged mice when compared to age-matched control mice who received a PBS injection. More importantly, significantly higher levels of Hsp27-specific CD4+ T cells were present in aged mice compared to young mice in both normal and ocular hypertensive (OHT) groups.
IOP elevation induced a higher degree of RGC loss in aged mice that is accompanied by higher levels of Hsp27-specific CD4+ T cells under both normal and OHT conditions, than in young mice. We propose that the immunological microenvironment of the eye contributes critically to the enhanced neurodegeneration following IOP elevation in old mice. Therefore, understanding age-related inflammatory changes in the retina may lead to a better knowledge of the pathogenesis of glaucoma in the elderly.
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