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Abstract #78502 Published in IGR 20-1
Commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma
Chen H; Cho KS; Vu THK; Vu THK; Shen CH; Shen CH; Kaur M; Chen G; Mathew R; McHam ML; McHam ML; Fazelat A; Fazelat A; Lashkari K; Au NPB; Au NPB; Tse JKY; Tse JKY; Li Y; Yu H; Yang L; Stein-Streilein J; Stein-Streilein J; Ma CHE; Ma CHE; Woolf CJ; Woolf CJ; Whary MT; Whary MT; Jager MJ; Fox JG; Fox JG; Chen J; Chen DFNature communications 2018; 9: 3209
See also comment(s) by Derek Welsbie •
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.
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Classification:
3.10 Immunobiology (Part of: 3 Laboratory methods)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
11.8 Neuroprotection (Part of: 11 Medical treatment)
