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Qiong Ding, Oliver W Gramlich, Michael G Anderson, Markus H Kuehn; Adoptive cell transfer from a glaucoma mouse model induces retinal ganglion cell loss in healthy recipient mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5717.
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There is mounting evidence that autoimmune processes can contribute to the pathophysiology of glaucoma in some patients. Data has also been presented to indicate that experimental induction of a retinal ganglion cell (RGC) directed autoimmune response in rodent models can lead to a RGC loss. Here we demonstrate that the recently described B6-Sh3pxd2 nee (nee) mouse model of glaucoma spontaneously develops an autoimmune response that can be transferred to normal recipient mice.
Spleen cells (5 x 106) from 2 months old nee or wild type (WT) mice were harvested and transferred to 2 months old WT mice (N=20) by tail vein injection. Mice were sacrificed after 4 month and serum samples and eyes were obtained. The number of surviving gamma synuclein immunoreactive RGC was determined in whole mount preparations of the retina. Differences between groups were evaluated using a one way ANOVA test. Additionally, eyes of 2 months old nee and WT mice were fixed in paraformaldehyde and used for immunohistochemical detection of CD4 and CD8.
Histological evaluation revealed an intact retina despite significant RGC loss in 2 month old nee mice. Immunohistochemistry invariably detected CD4 and CD8 positive cells along the basal surface of the retina and in the optic nerve head in nee mice, while these cells were absent in WT controls. Transfer of WT splenocytes to WT recipients did not cause a decline in RGC numbers (2447.22 vs 2527.41 RGC/mm2, p=0.69). However, spleen cells harvested from glaucomatous nee mice caused a significant decline in RGC numbers in normal recipient mice (1898.00 RGC/mm2, p=6.7x 10-5).
Our data indicate that in this mouse model CD4 and CD8 positive T-cells invade the retina and the optic nerve head, leading to the development of an autoimmune response. We further demonstrate this immune response can be transferred to healthy animals and cause RGC loss in healthy eyes in the absence of elevated IOP or other stressors.
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