Effects of Angiotensin II Type 1 (AT1–R) Receptor Blocker on Retinal Neuronal Cells in Inflammatory Status

Abstract

Purpose: : Angiotensin II is known as one of the regulators of retinal inflammation. In a present study, we investigate the influences of Angiotensin II and other inflammatory cytokines and in addition, therapeutic effects of an Angiotensin II type 1 receptor (AT1–R) blocker on retinal neuronal cells.

Methods: : Tissue localization and protein levels of AT1–R and AT2–R were examined by immunohistocehmistry and immunoblot analysis, respectively. Lipopolysaccharide (LPS) was injected into adult C57/B6 mice intraperitoneally to establish the model of retinal inflammation (endotoxin–induced uveitis) in which Angiotensin II is known to contribute to pathological reactions. Then, expression levels of Synaptophysin (presynaptic functional protein), Rhodopsin (major visual substance) and related molecules were analyzed with or without application of an AT1–R blocker, telmisartan. Moreover, the role of AT2–R, known to be upregulated in various pathological states, was evaluated by the administration of an AT2–R blocker. Finally, dark–adapted full–field electroretinography (ERG) was performed.

Results: : AT1–R and AT2–R were both expressed in the neural retina. Expression levels of Synaptophysin and Rhodopsin were downregulated in LPS–induced inflammatory retina, which were rescued following treatment with telmisartan. Strong STAT3 activation inhibited Rhodopsin expression. Inhibition of AT2–R partially reversed the therapeutic effects of telmisartan. ERG showed reduced amplitude of a–wave and prolonged implicit time of b–wave at LPS–induced inflammation, which was effectively prevented by treatment with telmisartan.

Conclusions: : Administration of an AT1–R blocker, telmisartan, maintained function of neural retina in terms of both molecular expression and physiological function.

Keywords: inflammation • photoreceptors • synapse