The retina is an easily accessible out-pouching of the central nervous system (CNS) and thus lends itself favourable to being a biomarker of the brain. Systematic Review Registration:, identifier CRD42020172953 IVTA, 4 mg, might be the best choice with lowest risk of IOP rising. ![]() However, SOC was associated with lower risk of side effects compared with FA implants. IVTA, 4 mg at 6 months was associated with lower risk of IOP rising compared with FA implant, 0.2 µg/day at 36 months (RR 3.43 95% CI 1.12–11.35).Ĭonclusion: No intravitreal therapeutic regimens showed a significant advantage or disadvantage with regard to efficacy. However, the FA implant, 0.59 mg was associated with a higher risk of cataract (RR 4.41, 95% CI 1.51–13.13) and raise in intraocular pressure (IOP) (RR 2.53 95% CI 1.14–6.25) compared with SOC at 24 months. Results: No specific regimen showed a statistically significant advantage or disadvantage to another treatment regimen with regard to efficacy. Methods: We searched the Cochrane Library database, EMBASE, Medline, until April 2021 with 13 RCTs (1806 participants) identified and conducted a pairwise and Bayesian network meta-analysis with random effects. Our results demonstrate that the transport of paeonol to the retina across the iBRB may involve the proton-coupled organic cation antiporter system, and the uptake of paeonol is changed by HG conditions.īackground: To compare the efficacy and safety of advanced intravitreal therapeutic regimens, including a dexamethasone implant at 350 and 700 μg a fluocinolone acetonide (FA) implant, 0.2 µg/day, 0.59 and 2.1 mg intravitreal bevacizumab, 1.25 mg intravitreal ranibizumab, 0.5 mg intravitreal triamcinolone acetonide (IVTA), 2 and 4 mg and standard of care (SOC, systemic therapy) for noninfectious uveitis. After being exposed to inflammatory conditions induced by glutamate, TNF-α, and LPS, paeonol and propranolol pretreat-ment significantly increased the uptake of both paeonol and propranolol in TR-iBRB cell lines compared to their respective controls. However, after the pretreatment of unlabeled paeonol in HG conditions, the mRNA levels of VEGF and HIF-1 were comparatively reduced, and the paeonol uptake rate was restored. Upon pre-incubation of these cell lines with high glucose (HG) media, paeonol uptake decreased and mRNA expression levels of angiogenetic factors, such as hypoxia inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) increased. In addition, transfections with OCTN1, 2 or plasma membrane monoamine transporter (PMAT) small interfering RNA did not affect paeonol uptake in TR-iBRB cell lines. This is consistent with the results obtained in vivo. Moreover, in vitro structural analog studies revealed that paeonol uptake was inhibited in the presence of organic cationic compounds including imperatorin, clonidine and tramadol. ![]() However, the uptake was unaffected by the absence of sodium or by membrane potential disruption. The uptake of paeonol by the TR-iBRB cell lines was found to be time-, concentration and nd pH-dependent. Conditionally immortalized rat retina capillary endothelial cells (TR-iBRB cell lines) were used as an in vitro model of the inner blood-retinal barrier (iBRB). However, para-aminohippuric acid, choline, and taurine had no effect on the RUI value. This value decreased significantly in the presence of imperatorin, tramadol, and pyrilamine when compared to the control. The retina uptake index (RUI) value of paeonol was dependent on both concentration and pH. The carotid artery single injection method was used to investigate the retina uptake index of paeonol. We aimed to investigate the transport mechanism of paeonol across the inner blood-retinal barrier both in vitro and in vivo. A R T I C L E I N F O Keywords: Blood-retina barrier Paeonol Proton-coupled organic cation antiporter Retina uptake index TR-iBRB cell lines High glucose medium condition A B S T R A C T Paeonol exerts various pharmacological effects owing to its antiangiogenic, antioxidant, and antidiabetic activities.
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