Low-dose Bevacizumab Decreases Ocular Hypotensive Effect of Angiotensin II in Sprague Dawley Rats.

PURPOSE: Although the effectiveness of anti-VEGF agents in ophthalmology has been thoroughly documented, we do not fully comprehend the epidemiology and mechanistic background of their side effects, including intraocular and systemic hypertension. Here, we investigate the interference of a low-dose bevacizumab with key neuronal and humoral mechanisms maintaining blood and intraocular pressure homeostasis. MATERIALS AND METHODS: Intraocular pressure (IOP), blood pressure (BP), and heart rate (HR) were measured in SPRD rats pretreated with bevacizumab or 0.9% NaCl at baseline and after infusion of angiotensin II, a humoral mediator involved in BP and IOP regulation. Superior cervical gangliectomy was performed to assess the effect of sympathetic nervous system on the analyzed parameters. Additionally, we studied the expression of a subset of genes related to renin-angiotensin system in the anterior segment of the eye. RESULTS: At baseline, there was no significant difference in IOP, BP, and HR between rats pretreated with 0.9% NaCl and bevacizumab. Infusion of angiotensin II lowered IOP in rats pretreated with 0.9% NaCl, but not in rats pretreated with bevacizumab (30 min: ∆4.22 ± 1.2 vs. baseline, p > .05; ∆0.83 ± 0.66 vs. baseline, p < .05) This effect was paralleled by an increased expression of angiotensin II type 1b and type 2 receptors in the anterior segment of the eye (AT1b: 1 ± 0.65 vs 7.35 ± 2.84, p < .05; AT2: 1 ± 0.05 vs. 12.8 ± 0.1, p < .05). Angiotensin II infusion increased BP in both groups (10 min: bevacizumab ∆44.6 ± 3.2, p < .05; 0.9%NaCl ∆37.1 ± 5.1, p < .05), whereas did not have any effect on HR. Sympathetic ocular denervation did not affect any of the analyzed parameters. CONCLUSIONS: We found that low-dose bevacizumab interferes with IOP-lowering properties of angiotensin II. This effect might be related to increased expression of angiotensin II receptors in the anterior segment of the eye.