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Stella Sarlos, Jennifer L. Wilkinson-Berka; The Renin-Angiotensin System and the Developing Retinal Vasculature. Invest. Ophthalmol. Vis. Sci. 2005;46(3):1069-1077. doi: 10.1167/iovs.04-0885.
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purpose. To determine the location and activity of renin–angiotensin system
(RAS) components in the developing rat retina and whether the RAS
influences retinal vascularization.
methods. Transgenic Ren-2 rats, which overexpress the RAS, and Sprague-Dawley
(SD) rats were studied at postnatal day (P)1, P7, P14, P21, and P90.
Immunohistochemistry was performed for angiotensinogen, prorenin,
angiotensin II (Ang II), and the angiotensin type 1 (AT1)
and 2 (AT2) receptors. Retinal active renin and prorenin
were measured by radioimmunoassay, and the density of
angiotensin-converting enzyme (ACE) by autoradiography. At P1 to P7,
Ren-2 and SD rats were administered either the ACE inhibitor lisinopril
(10 mg/kg per day, intraperitoneally [IP]) or the AT1 receptor antagonist losartan (10 mg/kg per day, IP), and vessel length
and density were measured.
results. At all time points, RAS components were localized to blood vessels and
cells in the ganglion cell layer. At P1, Ang II and both the
AT1 and AT2 receptors were on hyaloid vessels.
ACE binding increased in intensity from P1 to P90. Retinal renin was
mainly activated and was 5- to 15-fold higher in Ren-2 than in SD rats.
In Ren-2 rats, the growing vasculature extended farther into the
retinal periphery than in SD rats and was unchanged with either
lisinopril or losartan. Vascular density was increased in the periphery
of Ren-2 rats compared with SD rats and was reduced with lisinopril but
not with losartan.
conclusions. In the developing rat retina, a complete RAS is mainly found in blood
vessels and cells in the ganglion cell layer, where it may influence
the early stages of
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