| First Author | Chen G | Year | 2022 |
| Journal | Exp Eye Res | Volume | 219 |
| Pages | 109058 | PubMed ID | 35364100 |
| Mgi Jnum | J:324759 | Mgi Id | MGI:7266212 |
| Doi | 10.1016/j.exer.2022.109058 | Citation | Chen G, et al. (2022) CD38 deficiency protects the retina from ischaemia/reperfusion injury partly via suppression of TLR4/MyD88/NF-kappaB signalling. Exp Eye Res 219:109058 |
| abstractText | PURPOSE: This study aimed to explore cellular localisation of CD38 in the retina and evaluate the role and potential mechanism of CD38 deficiency in retinal ischaemia/reperfusion (I/R) injury. METHODS: Six-to eight-week-old male CD38 knockout (KO) and wild-type mice in C57BL/6 background were used. Immunostaining was performed to determine the cellular localisation of CD38 in the retina. Haematoxylin and eosin staining and immunostaining of Brn3a were used to evaluate the retinal I/R injury. Western blotting was performed to detect toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), p-p65, ionised calcium-binding adapter molecule 1, Sirtuin1 (Sirt1), Ac-p65, and pro-inflammatory cytokines protein expression. RESULTS: CD38 was highly expressed in mouse retinal microglia and astrocytes/Muller cells. CD38 deficiency reduced I/R-induced retinal damage and retinal ganglion cell death. Following retinal I/R injury, TLR4, MyD88, nuclear factor-kappaB p-p65 (NF-kappaB p-p65), pro-inflammatory cytokines and CD38 protein levels were also upregulated. After I/R injury, retinal inflammation factors IL-1beta, IL-6, and TNF-alpha mRNA and protein levels were increased. IL-1beta, IL-6, and TNF-alpha were reduced in CD38 KO mice after I/R injury. Retinal I/R injury induced the activation of microglia, but this effect was also suppressed by KO of CD38. Additionally, retinal I/R induced a significant increase in Ac-p65 protein levels and decrease in Sirt1 protein levels, while this effect was greatly attenuated by KO of CD38. CONCLUSION: CD38 deficiency protects the retina from I/R injury by suppressing microglial activation partly via activating Sirt1-mediated suppression of TLR4/MyD88/NF-kappaB signalling. |
