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. Jager, James G. Fox, Jianzhu Chen () and Dong F. Chen ()
Additional contact information
Huihui Chen: Second Xiangya Hospital of Central South University Changsha
Kin-Sang Cho: Harvard Medical School
T. H. Khanh Vu: Harvard Medical School
Ching-Hung Shen: Massachusetts Institute of Technology
Mandeep Kaur: Massachusetts Institute of Technology
Guochun Chen: Harvard Medical School
Rose Mathew: Harvard Medical School
M. Lisa McHam: Massachusetts Eye Health Service
Ahad Fazelat: Harvard Medical School
Kameran Lashkari: Harvard Medical School
Ngan Pan Bennett Au: City University of Hong Kong
Joyce Ka Yu Tse: City University of Hong Kong
Yingqian Li: Harvard Medical School
Honghua Yu: Harvard Medical School
Lanbo Yang: Harvard Medical School
Joan Stein-Streilein: Harvard Medical School
Chi Him Eddie Ma: City University of Hong Kong
Clifford J. Woolf: Children’s Hospital Boston, Harvard Medical School
Mark T. Whary: Massachusetts Institute of Technology
Martine J. Jager: Leiden University Medical Center
James G. Fox: Massachusetts Institute of Technology
Jianzhu Chen: Massachusetts Institute of Technology
Dong F. Chen: Harvard Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05681-9

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