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TH Wheeler-Schilling, E Zrenner, E Guenther, K Kohler; The Intrinsic Renin-Angiotensin System (RAS) Of The Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3626.
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Purpose: Recent studies imply a possible contribution of the RAS and its principal effector- and receptor molecules to the neurotransmission in the retina. Purpose of this study is to show the local existence of members of the RAS cascade (renin cleaves its substrate angiotensinogen (AGT) to form angiotensin I (AngI); AngI is converted by angiotensin converting enzyme (ACE) to angiotensin II (AngII)) and its receptors, which are mediated by two major subtypes AT1 and AT2, in the retina of various species and different developmental stages. Methods: Reverse transcription polymerase chain reaction (RT-PCR) was used to detect mRNAs for renin, AGT, ACE, and its receptors AT1 and AT2. In situ-hybridization (ISH) for the detection of renin and AT2-mRNA was applied. For the cellular localisation of the proteins by immunohistochemistry antibodies directed against renin, AngII, ACE, AT1 and AT2 were used. Additionally, we took advantage of a radioimmunoassay to detect the AngII-content. Results: The mRNAs for renin, AGT, ACE, AT1 and AT2 are expressed in the retina. Immunohistochemistry for AngII revealed labelled amacrine cells in the inner nuclear layer (INL) and fibers in sublayer 3 and 5 of the inner plexiform layer (IPL). ACE immunoreactive cells were detected in the INL and ganglion cell layer (GCL). A specific AT2 staining was observed in the GCL. In the INL horizontal cells and amacrine cells were stained at early stages (P3-P16) only. ISH for renin showed a labelling of the majority of cells in the GCL and less intense in the INL. Taken the level of blood-borne AngII as a baseline, the AngII-content in the retina was approximately ten times more. Conclusion: Renin, ACE, and AngII were localized in different cell populations of the retina and there seems to be a distinct distribution pattern of corresponding AT receptors. These results support the concept of a local RAS linked to neurotransmission/neuromodulation in the retina. In addition, putative roles of the cellular RAS in growth and development have to be addressed in the retina.
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