The angiostatic nature of pharmacological doses of glucocorticoid steroids is well known. However, the consequences of pathophysiological elevation of endogenous glucocorticoids are not well established. In the current study, we hypothesized that the angiostatic effect of corticosterone, an endogenous glucocorticoid in rodents, occurs through multi-faceted alterations in skeletal muscle microvascular endothelial cell proliferation, migration, and proteolysis. Chronic corticosterone treatment significantly reduced the capillary to fiber ratio in the tibialis anterior muscle compared to that of placebo-treated rats. Corticosterone inhibited endothelial cell sprouting from capillary segments ex vivo. Similarly, 3-dimensional endothelial cell spheroids treated with corticosterone for 48 hours showed evidence of sprout regression and reduced sprout length. Endothelial cell proliferation was reduced in corticosterone treated cells, coinciding with elevated FoxO1 and reduced VEGF production. Corticosterone treated endothelial cells exhibited reduced migration, which correlated with a reduction in RhoA activity. Furthermore, corticosterone treated endothelial cells in both 3-dimensional and monolayer cultures had decreased MMP-2 production and activation resulting in decreased proteolysis by endothelial cells, limiting their angiogenic potential. Promoter assays revealed that corticosterone treatment transcriptionally repressed MMP-2, which may map to a predicted GRE between −1510 and −1386 bp of the MMP-2 promoter. Additionally, Sp1, a known transcriptional activator of MMP-2 was decreased following corticosterone treatment. This study provides new insights into the mechanisms by which pathophysiological levels of endogenous glucocorticoids may exert angiostatic effects.
In eyes with persistent or recurrent idiopathic macular holes after standard PPV with internal limiting membrane peeling, repeat PPV with subretinal balanced salt solution injection to create a macular detachment may be a viable surgical treatment option. Our results show improved anatomical and visual outcomes postoperatively that compare favorably to other case series describing various surgical treatments for these challenging cases.
Background/aimsTo evaluate long-term visual outcomes of Boston type I keratoprosthesis (KPro) surgery and identify risk factors for visual failure.MethodsSingle surgeon retrospective cohort study including 85 eyes of 74 patients who underwent KPro implantation to treat severe ocular surface disease, including limbal stem cell deficiency, postinfectious keratitis, aniridia and chemical burns. Procedures were performed at the Centre hospitalier de l'Université de Montréal from October 2008 to May 2012. All patients with at least 5 years of follow-up were included in the analysis, including eyes with repeated KPro. Main outcome measures were visual acuity (VA), visual failure, defined as a sustained worse than preoperative VA, postoperative complications, and device retention.ResultsMean follow-up was 7.2±1.3 years (±SD). Mean VA was 2.1±0.7 (logarithm of minimal angle resolution) preoperatively and 1.9±1.2 at last follow-up. There were 2.4% of patients with VA better than 20/200 preoperatively and 36.5% at last follow-up. Maintenance of improved postoperative VA was seen in 61.8% of eyes at 7 years. Preoperative factors associated with visual failure were known history of glaucoma (HR=2.7 (1.2 to 5.9), p=0.02) and Stevens-Johnson syndrome (HR=7.3 (2.5 to 21.4) p<0.01). Cumulative 8-year complication rates were 38.8% retroprosthetic membrane formation, 25.9% hypotony, 23.5% new onset glaucoma, 17.6% retinal detachment, 8.2% device extrusion and 5.9% endophthalmitis. The majority (91.8%) of eyes retained the device 8 years after implantation.ConclusionAlmost two-thirds of patients had improved VA 7 years after KPro implantation. Preoperative risk factors for visual failure were known glaucoma and Stevens-Johnson syndrome.
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