Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma

Huihui Chen, Kin Sang Cho, T. H.Khanh Vu, Ching Hung Shen, Mandeep Kaur, Guochun Chen, Rose Mathew, M. Lisa McHam, Ahad Fazelat, Kameran Lashkari, Ngan Pan Bennett Au, Joyce Ka Yu Tse, Yingqian Li, Honghua Yu, Lanbo Yang, Joan Stein-Streilein, Chi Him Eddie Ma, Clifford J. Woolf, Mark T. Whary, Martine J. JagerJames G. Fox, Jianzhu Chen, Dong F. Chen*

*Corresponding author for this work

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Abstract

Glaucoma is the most prevalent neurodegenerative disease and a leading cause of blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are not fully understood. Here we show, using mice deficient in T and/or B cells and adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is sufficient to induce T-cell infiltration into the retina. This T-cell infiltration leads to a prolonged phase of retinal ganglion cell degeneration that persists after IOP returns to a normal level. Heat shock proteins (HSP) are identified as target antigens of T-cell responses in glaucomatous mice and human glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with human and bacterial HSPs; mice raised in the absence of commensal microflora do not develop glaucomatous T-cell responses or the associated neurodegeneration. These results provide compelling evidence that glaucomatous neurodegeneration is mediated in part by T cells that are pre-sensitized by exposure to commensal microflora.

Original languageEnglish
Article number3209
Number of pages13
JournalNature Communications
Volume9
Issue number1
DOIs
Publication statusPublished - 10 Aug 2018

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