| First Author | He C | Year | 2023 |
| Journal | Sci Transl Med | Volume | 15 |
| Issue | 707 | Pages | eadg1656 |
| PubMed ID | 37531415 | Mgi Jnum | J:343753 |
| Mgi Id | MGI:7567737 | Doi | 10.1126/scitranslmed.adg1656 |
| Citation | He C, et al. (2023) Gut-licensed beta7(+) CD4(+) T cells contribute to progressive retinal ganglion cell damage in glaucoma. Sci Transl Med 15(707):eadg1656 |
| abstractText | Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4(+) T cells expressing a gut-homing integrin beta7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, beta7(+) CD4(+) T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced beta7(+) CD4(+) T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing beta7(+) CD4(+) T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing beta7(+) CD4(+) T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed beta7(+) CD4(+) T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the "gut-retina" axis in glaucoma. |
