Neuronal and glial cell expression of angiotensin II type 1 (AT 1) and type 2 (AT 2) receptors in the rat retina

Abstract

The bio-active peptide, angiotensin II (Ang II), has been suggested to exert a neuromodulatory effect on inner retinal neurons. In this study, we examined the distribution of angiotensin receptors (ATRs) in the developing and mature rat retina and optic nerve using immunofluorescence immunocytochemistry. Double-labeling experiments were performed with established markers to identify different retinal cell populations. In adult retinae, ATRs were observed on neurons involved in “ON” pathways of neurotransmission. Angiotensin II type 1 receptors (AT 1Rs) were expressed by a sub-population of “ON” cone bipolar cells that also labeled for Gα 0 and islet-1. Extra-neuronal expression of AT 1Rs was evident on retinal astrocytes, Müller cells and blood vessels. Immunoreactivity for the angiotensin II type 2 receptor (AT 2R) was observed on conventional and displaced GABAergic amacrine cells. Co-localization studies showed that AT 2R-expressing amacrine cells constituted at least two separate sub-populations. Cell counts revealed that all wide-field amacrine cells expressing protein kinase C-alpha were also AT 2R-positive; a further subset of amacrine cells expressing AT 2Rs and stratifying in sublamina “b” of the inner plexiform layer (IPL) was identified. Developmental expression of AT 1Rs was dynamic, involving multiple inner neuronal classes. At postnatal day 8 (P8), AT 1R immunoreactivity was observed on putative ganglion cells. The characteristic bipolar cell labeling observed in adults was not evident until P13. In contrast, AT 2Rs were detected as early as P2 and localized specifically to amacrine cells from this age onward. These data provide further evidence for the potential role of angiotensin II in the modulation of retinal neurons and glia. The differential pattern of expression of these receptors across these cell types is similar to that observed in the brain and suggests that a similar functional role for Ang II may also exist within the retina.