The circulating renin-angiotensin system (RAS) is an important determinant in maintaining adequate systemic blood pressure and may also modify organ- specific blood flow. Monoclonal or affinity-purified antibodies are available against five major components of the RAS: angiotensinogen, prorenin, renin, angiotensin-converting enzyme, and angiotensin II. The latter directly stimulates vascular smooth muscle contraction. Angiotensin II may also be generated locally in peripheral tissues via a local RAS, e.g., AII receptors and the five RAS components mentioned are reported to exist in the brain, and at least some RAS components seem to be synthesized there. A local RAS has been proposed for the eye and may be essential in the autoregulation of retinal blood flow in health and disease. Current data on the localization of an intraocular RAS are limited to only a few observations. In this grant application, immunostaining of the five major RAS components mentioned above and of AII receptors in the normal and diabetic human and rat eye is proposed. Light and electron microscopic techniques are to be used in an effort to obtain basic new anatomic and histologic information about the presence, distribution, and intensity gradients of immunostaining, which in turn will delineate hypotheses regarding production, transport, and activation of intraocular RAS components. Hyperactive RAS components may modify diabetic microvascular disease and may be treatable by inhibitors of AII formation.
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