IL-10 inhibits retinal pigment epithelium cell proliferation and migration through regulation of VEGF in rhegmatogenous retinal detachment

Abstract

Rhegmatogenous retinal detachment (RRD) is a disorder of the eye that affects physical and mental health. Retinal pigment epithelium (RPE) is closely associated with RRD, and it is hypothesized that RPE-secreted inflammatory cytokines may induce early pathological changes of RRD and may participate in RPE proliferation and migration. The present study determined a role for interleukin (IL)‑10 as an RPE‑secreted immune regulatory factor that contributes to RRD. A rat RRD model was established and RPE cells were isolated and cultivated. RPE cells were randomly divided into four groups, three treated with different concentrations of IL‑10 (100, 50, and 20 mM) and one untreated. RPE cell proliferation was evaluated by MTT assay and the activity of caspase‑3 was also measured. RPE cell invasion was determined by Transwell assay. Vascular endothelial growth factor A (VEGF) expression was examined by reverse transcription‑quantitative polymerase chain reaction and western blotting; IL‑1 and IL‑6 levels were measured by ELISA. IL‑10 treatment suppressed RPE cell proliferation and migration, promoted caspase‑3 activity, inhibited VEGF mRNA and protein expression, and downregulated the secretion of inflammatory cytokines IL‑1 and IL‑6 in RRD group compared with the untreated Model group. The aforementioned effects of IL‑10 became more evident with increasing IL‑10 concentration. IL‑10 suppressed inflammation, facilitated RPE cell apoptosis and inhibited cell proliferation and migration through the regulation of VEGF expression.

The complement C3a‑C3aR and C5a‑C5aR pathways promote viability and inflammation of human retinal pigment epithelium cells by targeting NF‑κB signaling

“…Damage to the RPE layer and the underlying choroid may promote infiltration of immune cells and induce retinal microglia and choroidal inflammatory cells to release pro-inflammatory cytokines. A previous study suggested that the anti-inflammatory cytokine IL-10 inhibits RPE cell proliferation and inflammation through the regulation of VEGF in RRD rats ( 39 ), a finding that is consistent with the role of IL-10 in C3a-C3aR- or C5a-C5aR-induced RPE cells. However, the role of C3a-C3aR or C5a-C5aR in the regulation of RPE and immune cells at the retina-choroidal interface remains to be investigated.…”

Anti-Inflammatory and Anti-Oxidative Synergistic Effect of Vitamin D and Nutritional Complex on Retinal Pigment Epithelial and Endothelial Cell Lines against Age-Related Macular Degeneration

“…The anti-inflammatory role of IL-10 has been shown in a CNV mouse model, where IL-10 deficiency increased inflammation and subsequent intraocular injection enhanced the volume of neovascularization [ 88 ]. Similarly, IL-10 increased the secretion of the proinflammatory cytokine IL-6 through regulation of VEGF production and is implicated in the prevention of the development of rhematogeneous retinal detachment [ 89 ]. Interestingly, our results are consistent with a recent study [ 36 ], revealing that the elevated IL-10 expression levels under LPS-induced inflammatory conditions remained unmodified after application of either N or ND in both cell lines, thus suggesting a protective role of vitamin D against inflammation.…”

Vitreous Cytokine Expression and a Murine Model Suggest a Key Role of Microglia in the Inflammatory Response to Retinal Detachment

“…A recent paper demonstrated that IL-10 inhibited both VEGF expression and proliferation of cultured retinal pigmented epithelial cells isolated from rat eyes following RD. 37 …”