Glucocorticoid Receptor ß Induces Hepatic Steatosis by Augmenting Inflammation and Inhibition of the Peroxisome Proliferator-activated Receptor (PPAR) α.

Glucocorticoids (GCs) regulate energy supply in response to stress by increasing hepatic gluconeogenesis during fasting. Long-term GC treatment induces hepatic steatosis and weight gain. GC signaling is coordinated via the GC receptor (GR) GRα, as the GRß isoform lacks a ligand-binding domain. The roles of the GR isoforms in the regulation of lipid accumulation is unknown. The purpose of this study was to determine whether GRß inhibits the actions of GCs in the liver, or enhances hepatic lipid accumulation. We show that GRß expression is increased in adipose and liver tissues in obese high-fat fed mice. Adenovirus-mediated delivery of hepatic GRß overexpression (GRß-Ad) resulted in suppression of gluconeogenic genes and hyperglycemia in mice on a regular diet. Furthermore, GRß-Ad mice had increased hepatic lipid accumulation and serum triglyceride levels possibly due to the activation of NF-κB signaling and increased tumor necrosis factor α (TNFα) and inducible nitric-oxide synthase expression, indicative of enhanced M1 macrophages and the development of steatosis. Consequently, GRß-Ad mice had increased glycogen synthase kinase 3ß (GSK3ß) activity and reduced hepatic PPARα and fibroblast growth factor 21 (FGF21) expression and lower serum FGF21 levels, which are two proteins known to increase during fasting to enhance the burning of fat by activating the ß-oxidation pathway. In conclusion, GRß antagonizes the GC-induced signaling during fasting via GRα and the PPARα-FGF21 axis that reduces fat burning. Furthermore, hepatic GRß increases inflammation, which leads to hepatic lipid accumulation.

Survival in Patients with Neovascular Glaucoma Following Tube Shunt Implant or Cyclodestructive Procedure.

Purpose: The study purpose was to assess patient survival after tube shunt implant or cyclodestructive procedure for neovascular glaucoma and to determine whether specific preoperative factors are predictive of survival. Materials and methods: A retrospective chart review was performed on patients with neovascular glaucoma who underwent tube shunt implant and/or cyclodestructive procedure between January 2002 and December 2019 at the Minneapolis Veterans Affairs Health Care System. Patient survival was compared to the age and gender-matched Minnesota population. Cox regression analyses were performed to evaluate preoperative parameters and survival. Results: Tube shunt alone was implanted in 30 eyes, cyclodestruction alone was performed in nine eyes, and two eyes underwent both (n = 41 eyes, 39 patients). The postoperative 5-year survival rate was 62% in neovascular glaucoma patients compared to 80% in controls. Survival did not differ significantly based on neovascular glaucoma etiology. Preoperative best-corrected visual acuity of the neovascular glaucoma-affected eye (p = 0.05) and Charlson Comorbidity Index (p = 0.02) were associated with survival, but preoperative maximum intraocular pressure, hemoglobin A1c, and creatinine were not. The mean intraocular pressure at 6 months postprocedure was 14 mm Hg for tube shunt and 27 mm Hg for cyclodestruction (p = 0.03). Conclusion: Neovascular glaucoma patients have reduced survival, but the majority survived at least 5-year postprocedure. Ophthalmologists should consider patient survival and factors predictive of survival when planning procedures for neovascular glaucoma. Clinical significance: Our findings provide an updated perspective on survival in the setting of neovascular glaucoma and can help ophthalmologists provide patient-centered and holistic care. How to cite this article: Zhou Y, Coleman S, Boysen J, et al. Survival in Patients with Neovascular Glaucoma Following Tube Shunt Implant or Cyclodestructive Procedure. J Curr Glaucoma Pract 2022;16(2):74-78.