IL-2 promotes cell migration, ECM synthesis and TGF-β2 expression in RPE cells via JAK/STAT3 and NF-κB signaling pathways, which may play an important role in proliferative vitreoretinopathy.
The left eyes, respectively, received an intravitreal injection as follows: normal saline (G1), rAAV2-control small interfering RNA (siRNA) (G2), rAAV2-TGF-β2-siRNA (G3), rAAV2-PDGF-B-siRNA (G4), rAAV2-TGF-β2-siRNA and rAAV2-PDGF-B-siRNA (G5, G6) on day 3 after PVR induction.
The amount and activity of this enzyme appears to be related to the differentiation state of the RPE cells and their stimulation by TGF-beta2, a growth factor known to be increased in the vitreous of PVR.
These results indicated that application of the dCas9 targeted to the P2 of MDM2 is a potential therapeutic approach to diseases due to the P2-driven aberrant expression of Mdm2 - such as proliferative vitreoretinopathy.
The signaling pathway comprising the PI3Ks, along with a Ser/Thr kinase (AKT), a proto-oncogene product (mouse double minute (MDM)2), and a tumor suppressor protein (p53), plays an essential role in experimental proliferative vitreoretinopathy (PVR), which is a fibrotic blinding eye disorder.
Resveratrol inhibits VEGF expression in human adult RPE cells and limits the development of proliferative vitreoretinopathy, by attenuating transforming growth factor-β2-induced wound closure and cell migration.
Subretinal injection of vascular endothelial growth factor (VEGF) and Matrigel induced a late-onset vitreoretinal inflammation that gradually developed into PVR.
Interleukin (IL)-10, IL-12p40, IL-6, monocyte chemotactic protein-1, and vascular endothelial growth factor (VEGF) in the SOF with PVR were significantly higher than in those with RRD or MHRD.
The cytokine array also showed that TNF-α levels were normal and that corticosteroid-sensitive pathways were absent in fibrotic NIV, helping explain prior failure of these conventional therapeutic approaches.
Furthermore, our experimental results demonstrated that MDM2T309G in hPRPE cells enhanced vitreous-induced cell proliferation and survival, suggesting that this SNP contributes to the pathogenesis of PVR.
Blood from 450 patients with (138 cases) and without (312 controls) post-rhegmatogenous retinal detachment (RD) PVR was genotyped to determine polymorphisms located in the TNFα gene.
HB-EGF expression in fibroproliferative tissue and its stimulatory effect on glial cell proliferation, chemotaxis, and VEGF secretion suggest that HB-EGF may be a factor mediating glial cell responses during PVR.
The presence of mRNA coding for the cytokines interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF alpha) was investigated in 19 epiretinal membranes obtained from eyes undergoing vitrectomy for the treatment of retinal detachment complicated by proliferative vitreoretinopathy.
Vitreal growth factors activate their respective receptors of cells in the vitreous, trigger their downstream signaling transduction (e.g. phosphoinositide 3 kinases (PI3Ks)/Akt), and drive cellular responses intrinsic to the pathogenesis of PVR.