Tumor necrosis factor-alpha (TNF-alpha), a major inflammatory factor released from activated retinal glial cells, is implicated in the pathogenesis of glaucoma. In this study, we investigated whether and how TNF-alpha may affect functional conditions of activated retinal Muller cells. Our results showed that in the group I metabotropic glutamate receptor (mGluR I) agonist DHPG-activated cultured Muller cells, TNF-a treatment aggravated cell gliosis, as evidenced by significantly increased expression of glial fibrillary acidic protein (GFAP). TNF-alpha treatment of the DHPG-activated Muller cells decreased cell proliferation and induced cell apoptosis. In normal Muller cells, TNF-alpha treatment increased the mRNA levels of leukocyte inhibitory factor (LIF), intercellular cell adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), and chemokine C-C-motif ligand 2 (CCL2), which could be significantly attenuated when Muller cells were pre-activated. However, TNF-alpha-induced elevation in mRNA levels of inflammatory factors, such as TNF-alpha, inducible nitric oxide synthase (iNOS), and interleukin-6 (IL-6), in normal Muller cells still kept higher levels when Muller cells were pre-activated. Furthermore, the TNF-alpha-induced changes of cytokines were partially mediated by NF-kappa B signaling pathway. Our results suggest that TNF-alpha may promote gliosis and inflammatory response of activated Muller cells, thus aggravating RGC injury in glaucoma. (c) 2020 Elsevier Inc. All rights reserved.