Angiotensin II Receptor Blocker (ARB) Therapy in a Chronic Glaucoma Model: Initial Findings
Gillian J McLellan BVMS PhD University of Wisconsin-Madison, Ophthalmology and Visual Sciences
Co-authors: Julie A Kiland MS Ryan Lopez Kazuya Oikawa DVM
Our study aims to determine the effects of ARB administration on IOP, blood pressure (BP) and ocular perfusion pressure (OPP); aqueous humor (AH) and serum TGFβ2, and optic nerve head (ONH) gene expression in feline congenital glaucoma (FCG). Fourteen 6-month-old LTBP2-/- FCG and 6 age-matched untreated wt cats were enrolled in the study. FCG cats were randomly assigned to receive oral telmisartan (1mg/kg/day) or placebo for 6 months. IOP and BP were measured weekly by rebound tonometry and oscillometric method, respectively, by observers masked to treatment. Aqueous humor (AH) and serum were collected pre-treatment and after 6 months of treatment and concentrations of total TGFβ2 measured by ELISA. At the conclusion of the treatment period, total RNA was extracted from ONHs for RNA-seq (Nova-seq) followed by bioinformatic analyses that included differential expression (DE; DESeq2) and functional enrichment (g:Profiler) analyses. Statistical comparisons between groups used ANOVA with Tukey-Kramer correction for multiple comparisons (p1.5). Functional enrichment analysis identified inflammatory responses as the most significantly upregulated molecular pathways in telmisartan-treated FCG compared to normal controls. We did not identify significant transcriptomic evidence for mitigation of neuro-inflammation by ARB administration in this small cohort of FCG cats.
Funding Sources: BrightFocus Foundation; NIH grants R01 EY027396 and P30 EY0016665; JASSO; Research to Prevent Blindness.
