Its activation results in the production of type I interferons, and enhancement of apoptosis

d not show any significant change in the elevated IOP. These in vivo data demonstrated that D+I reduced the IOP for up to 30 days and they were well tolerated by the animals. This feature is a tremendous advantage of any controlled drug delivery system because this avoids drug loss to systemic circulation since eye drops might Scutellarein web PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19667973 lead to drug wastage and potential side effects [34]. Furthermore, eye drops are susceptible to rapid tear turnover resulting in low corneal bioavailability and rapid clearance. In this way, eye drops require frequent instillation with large drug loadings to maintain the drug concentration within the therapeutic window [39]. Noteworthy, the ocular hypotensive effect promoted by D+I did not interfere in the MAP. This characteristic is desirable for any antiglaucomatous drug PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19668191 or formulation as it increases its specificity reducing potential side effects. The pathophysiological rationality to explore modulators of the RAS as antiglaucomatous agents come from previous studies. For instance, the effects of blockers of the ACE/Ang II/AT1 receptor axis on IOP have been evaluated in animals [40�42] and patients with glaucoma [43� 45]. Recently, we have proposed activation of ACE2 as a new strategy to develop drugs to treat glaucoma since this approach increases the inactivation of Ang II and production of Ang-(1�7) [26]. Indeed, our present findings showed that increased activity of endogenous ACE2 promoted by ocular inserts containing DIZE reduced the IOP of glaucomatous rats. Interestingly, activation of ACE2 also induces beneficial effects on uveitis [46]. Thus, these findings, in addition to data reporting the expression of ACE2 in both human [47] and rodent retinas [26, 48] and the effectiveness of DIZE