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Editors Selection IGR 7-2

Medical treatment: Angiotensin antagonists

Comment by Thomas Yorio on:

12348 Effect of CS-088, an angiotensin AT1 receptor antagonist, on intraocular pressure in glaucomatous monkey eyes, Wang RF; Podos SM; Mittag TW et al., Experimental Eye Research, 2005; 80: 629-632

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The rennin-angiotensin system (RAS) is known to play a role in blood pressure control and electrolyte fluid balance. In the eye, the role of the RAS system is less clear. Previous observations have shown that angiotensin II antagonists or synthesis inhibitors (ACE-inhibitors) can lower IOP when administered systemically. More recently, CS-088, an angiotensin AT1-receptor antagonist, was shown to lower IOP in rabbits when administered topically. In the present report by Wang et al. (461), CS-088 was shown to lower IOP in the primate model of glaucoma. The authors were able to demonstrate that repeated administration of CS-088 at the 2 and 4% doses resulted in a dose-dependent reduction of IOP that was significant and sustained over multiple days of treatment. This was particularly important as it demonstrates that repeated dosing does not result in tachyphylaxis or inflammation. These observations support the notion that the RAS may be a clinically important site for regulating IOP. Although no mechanism of action studies were reported, the authors reference data from rabbits (Inoue et al. Curr Eye Res 2001; 23: 133-138) that suggest AT₁ receptor antagonists enhance uveoscleral outflow without affecting formation or normal aqueous outflow pathways. They further speculate that angiotensin AT¹ antagonists may be beneficial for the treatment of glaucoma not only for their IOP lowering effect but also for blocking angiotensin II mediated apoptosis that may occur at the retinal ganglion cells. Unfortunately, there was no data in this study to support this notion, but it does remain a possible action that needs to be investigated.

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