Anti-Vascular Endothelial Growth Factor Therapy Abolishes Glioma-Associated Endothelial Cell-Induced Tumor Invasion.

Tumor-remodeled endothelial cells not only facilitate the formation of tumor angiogenesis but also promote tumorigenesis. In this study, we aimed to explore the interaction between glioma-associated endothelial cells (GAEs) and glioma cells. We found that different subtypes of glioma owned distinct GAE abundance. Glioma patients with high GAE abundance exhibited poor prognosis. Both the results of the bioinformatics analysis and the in vitro co-culture system assay revealed that GAE promoted glioma cell invasion. Besides, anti-vascular endothelial growth factor (VEGF) therapy partially abolished the effects of GAE on gliomas. Moreover, anti-VEGF therapy upregulated IL-2 expression in GAE, and exogenous IL-2 administration inhibits GAE-induced glioma cell invasion. Collectively, our present study provides a novel outstanding of the interaction between GAE and glioma cells.

Efficacy of microcatheter-assisted trabeculotomy on secondary glaucoma after congenital cataract surgery.

AIM: To evaluate efficacy of microcatheter-assisted trabeculotomy (MAT) in eyes with secondary glaucoma after congenital cataract surgery and explore its correlation with the different degree of trabeculotomy. METHODS: A retrospective analysis was conducted on patients who underwent the said procedure between September 2019 and September 2020. The patients were classified into two groups according to the degree of trabeculotomy (group 1: ≤240-degree; group 2: 240-360-degree). The intraocular pressure (IOP) and anti-glaucoma drugs before and after operation was collected during the 12-month follow-up. RESULTS: Totally 27 eyes of 25 patients were included: 11 (40.7%) eyes in group 1 and 16 (59.3%) eyes in group 2. The mean IOP of all patients was 34.67±9.18 mm Hg preoperatively and 8.74±4.32, 9.95±5.65, 14.39±5.30, 16.02±4.37, 15.82±3.28, and 16.19±3.56 mm Hg 1d, 1wk, 1, 3, 6, and 12mo after surgery, respectively. In all patients, there were significant differences in IOP at each time point (F=65.614, P<0.01). In each group, IOP after surgery was lower than that before surgery (all P<0.01), but there was no difference in the rate of IOP reduction between the two groups (P=0.246). Furthermore, the amount of anti-glaucoma medications reduced to 0.30±0.67 (0-2) at 12mo from 2.63±0.49 (2-3) preoperatively (P<0.01), and there was no difference between the two groups (P>0.05). At the end of follow-up, the partial success rate was 81.8% in group 1 vs 93.75% in group 2 (P=0.549). Various amount of intraoperative and postoperative hyphema occurred in all eyes, which spontaneously absorbed or cleaned through paracentesis and irrigation. No other serious complications was observed. CONCLUSION: MAT can effectively reduce IOP in patients with secondary glaucoma after congenital cataract surgery with a high success rate and safety. And it can be used as the first choice for the treatment of secondary glaucoma after surgery for congenital cataracts.

Total glucosides of paeony suppresses experimental autoimmune uveitis in association with inhibition of Th1 and Th2 cell function in mice.

Total glucosides of paeony (TGP) are active components extracted from the roots of Paeonia lactiflora Pall. In this study, we investigated the role and mechanisms of TGP in experimental autoimmune uveitis (EAU) model of mice. The C57BL/6 mice were randomly divided into three groups: sham group, EAU-control group, and EAU-TGP group. Clinical score of images of the eye fundus were taken on 7, 14, 21, and 28 days after induction of EAU. The concentrations of proinflammatory cytokines in intraocular fluid were measured at 14 days after EAU induction with the use of a multiplex assay system. Flow cytometry was used to analyze the frequency of CD4+, CD8+, interferon-gamma (IFN-γ), and CD4+/CD8+ ratio in spleen and lymph nodes. Western blotting was used to measure expressions of mitogen-activated protein kinase (MAPK) pathway-related proteins in retina. Clinical scores for uveitis were lower in TGP-treated EAU mice than those without TGP treatment. Importantly, the concentrations of cytokines induced by T-helper 1 (Th1) and T-helper 2 (Th2) cells in intraocular fluid were reduced in EAU mice treated with TGP. Furthermore, the frequency of CD4+, IFN-γ, and CD4+/CD8+ ratio was decreased and the frequency of CD8+ was increased in spleen and lymph nodes of mice treated with TGP. The anti-inflammatory effects of TGP were mediated by inhibiting the MAPK signaling pathways. Our results showed that TGP suppressed uveitis in mice via the inhibition of Th1 and Th2 cell function. Thus, TGP may be a promising therapeutic strategy for uveitis, as well as other ocular inflammatory diseases.

Research on the comparison of the demethylvancomycin's diffusion-deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection.

PURPOSE: To compare the demethylvancomycin's diffusion-deposition characteristics in the ocular solid tissues of sustained subtenon drug delivery with subconjunctival injection. METHOD: Sixty adult white rabbits were randomly assigned to the subtenon drug delivery group and the subconjunctival injection group. The subtenon drug delivery group was continuously infused demethylvancomycin to the subtenon of rabbits. The subconjunctival injection group was injected demethylvancomycin to the subconjunctival of rabbits. Cornea, iris and sclera were collected for high-performance liquid chromatography analyses to determine drug concentrations at one hour, three hours, six hours, 12 h and 24 h of drug administration. WinNonlin 6.3 was used to calculate the parameters of cumulative area under the curve (AUCcum) of demethylvancomycin. RESULTS: The peak levels of demethylvancomycin concentration of the subtenon drug delivery group and the subconjunctival injection group were 92.406 ± 21.555 and 51.778 ± 14.001 µg/g in cornea, 28.451 ± 10.229 µg/g and 42.271 ± 27.291 µg/g in iris, 153.166 ± 51.738 µg/g and 57.423 ± 18.480 µg/g in sclera. The differences of concentrations between the two groups in cornea and sclera were statistically significant (F = 487.775, p < 0.001; F = 132.748, p < 0.001). The difference in iris was not statistically significant (F = 4.848, p = 0.064). The maximum of AUCcum of the subtenon drug delivery group and the subconjunctival injection group was 1808.23 h * µg/g and 273.73 h * µg/g in cornea, 489.12 h * µg/g and 216.16 h * µg/g in iris and 2166.34 h * µg/g and 392.57 h * µg/g in sclera at 24 h of drug administration. CONCLUSION: The sustained subtenon drug delivery had a better drug permeability and accumulation in the intraocular solid tissue compared to subconjunctival injection, which demonstrated it was probably a promising and effective approach for treating posterior segment diseases and endophthalmitis.