Angiotensin II and its receptor subtypes in the human retina.
OBJECTIVE
To quantify and evaluate the distribution of angiotensin II (Ang II) and its receptors in the human retina.


METHODS
Donor eyes were obtained within 12 hours postmortem and classified as hypertensive or normotensive and diabetic or nondiabetic, based on the donors' medical histories. Ang II in retina and vitreous was quantified by RIA. Ang II receptors were characterized and quantified by competitive membrane-binding assays. Ang II, its heptapeptide metabolite Ang-(1-7), and AT1 and AT2 receptors were localized by immunohistochemistry and confocal imaging.


RESULTS
Levels of Ang II in the retina were significantly higher than in vitreous (P < 0.05). Ang II in the diabetic retina had a higher median compared with that in the nondiabetic retina. Ang II and Ang-(1-7) colocalized in retinal Müller cells. The retina had the highest levels of Ang II receptors that were significantly higher than the optic nerve, retinal pigment epithelium-choroid complex, and ciliary body-iris complex (P < 0.05). AT1 receptors were more abundant than AT2 receptors in the retina. Immunoreactivity for AT1 was detected in Müller cells and on blood vessels. AT2 receptors were localized throughout the Müller cells and nuclei of ganglion cells and neurons in the inner nuclear layer.


CONCLUSIONS
In the human retina, identification of Ang II and its bioactive metabolite Ang-(1-7) in Müller cells suggests that these glial cells are able to produce and process Ang II. Ang receptors were localized in the blood vessels and neural cells. Local Ang II signaling may thus allow for autoregulation of neurovascular activity. Such an autonomous system could modulate the onset and severity of retinovascular disease.
Senanayake
Preenie deS
Pd
Department of Ophthalmology, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. senanap@ccf.org
Drazba
Judy
J
Shadrach
Karen
K
Milsted
Amy
A
Rungger-Brandle
Elisabeth
E
Nishiyama
Kazutoshi
K
Miura
Shin-Ichiro
S
Karnik
Sadashiva
S
Sears
Jonathan E
JE
Hollyfield
Joe G
JG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D001667:Binding, Competitive; D015153:Blotting, Western; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011863:Radioimmunoassay; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D014019:Tissue Donors
D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)