| First Author | Lee JJ | Year | 2015 |
| Journal | Invest Ophthalmol Vis Sci | Volume | 56 |
| Issue | 5 | Pages | 3041-50 |
| PubMed ID | 26024088 | Mgi Jnum | J:230965 |
| Mgi Id | MGI:5766596 | Doi | 10.1167/iovs.15-16504 |
| Citation | Lee JJ, et al. (2015) High-fat diet induces toll-like receptor 4-dependent macrophage/microglial cell activation and retinal impairment. Invest Ophthalmol Vis Sci 56(5):3041-50 |
| abstractText | PURPOSE: The toll-like receptor 4 (TLR4) signaling pathway is involved in chronic inflammation and insulin resistance, which are associated with obesity and diabetes mellitus. In the present study, a model of high-fat diet (HFD) feeding of mice was used to investigate the role of TLR4 in overnutrition- and obesity-associated inflammation and infiltration of macrophages and microglia in the retina. METHODS: Wild-type C57BL/6 and TLR4 knockout (TLR4KO; B6.B10ScN-Tlr4(lps-del)/JthJ) mice were fed a HFD or control chow diet (CD) for 6 months. The TLR4 expression, the relative increase in macrophages/microglia (CD11b(+) and CD45(+) cells), the presence of markers of oxidative stress (gp91phox and malondialdehyde; MDA), and DNA damage (phosphorylated histone H2AX; gammaH2AX) were assessed by real-time PCR and immunofluorescence studies. RESULTS: The HFD for 6 months showed increased obesity, glucose intolerance, and insulin resistance in mice. Toll-like receptor 4 expression was found in vascular pericytes at the inner retina. Increased CD11b(+) and CD45(+) cells, phosphorylated NF-kappaB, interleukin-6, gp91phox, MDA, and gammaH2AX were observed in the retina of mice fed a HFD compared to CD counterparts. TLR4KO mice did not show the adverse effects of HFD. CONCLUSIONS: Our results indicate that HFD-induced macrophage/microglial cell activation and retinal impairment were reduced in the absence of TLR4. The findings suggest that TLR4 is implicated in the pathogenesis of retinal diseases caused by metabolic disorders. |
