| First Author | Hu SJ | Year | 2015 |
| Journal | J Neurosci | Volume | 35 |
| Issue | 18 | Pages | 6987-96 |
| PubMed ID | 25948251 | Mgi Jnum | J:221649 |
| Mgi Id | MGI:5641275 | Doi | 10.1523/JNEUROSCI.3955-14.2015 |
| Citation | Hu SJ, et al. (2015) Upregulation of P2RX7 in Cx3cr1-Deficient Mononuclear Phagocytes Leads to Increased Interleukin-1beta Secretion and Photoreceptor Neurodegeneration. J Neurosci 35(18):6987-96 |
| abstractText | Photoreceptor degeneration in age-related macular degeneration (AMD) is associated with an infiltration and chronic accumulation of mononuclear phagocytes (MPs). We have previously shown that Cx3cr1-deficient mice develop age- and stress- related subretinal accumulation of MPs, which is associated with photoreceptor degeneration. Cx3cr1-deficient MPs have been shown to increase neuronal apoptosis through IL-1beta in neuroinflammation of the brain. The reason for increased IL-1beta secretion from Cx3cr1-deficient MPs, and whether IL-1beta is responsible for increased photoreceptor apoptosis in Cx3cr1-deficient mice, has not been elucidated. Here we show that Cx3cr1-deficient MPs express increased surface P2X7 receptor (P2RX7), which stimulates IL-1beta maturation and secretion. P2RX7 and IL-1beta inhibition efficiently blunted Cx3cr1-MP-dependent photoreceptor apoptosis in a monocyte/retina coculture system and in light-induced subretinal inflammation of Cx3cr1-deficient mice in vivo. Our results provide an explanation for increased CX3CR1-dependent IL-1beta secretion and suggest that IL-1beta or P2RX7 inhibition can help inhibit the inflammation-associated photoreceptor cell loss in late AMD, including geographic atrophy, for which no efficient treatment currently exists. |
