Submitted on February 15, 2008
Revised on September 4, 2008
Accepted on October 11, 2008
Regulation of Angiotensin II receptors and extracellular matrix turnover in Human Retinal Pigment Epithelium: Role of Angiotensin II
Gary E Striker1, Francoise Praddaude2, Oscar Alcazar3, Scott W Cousins4, and Maria Marin-Castano3*
1 Mount Sinai School of Medicine
2 University of Toulose, School of Medicine
3 Bascom Palmer Eye Institute, University of Miami
4 Duke University Eye Center, Durham
* To whom correspondence should be addressed. E-mail: Mcastano{at}med.miami.edu.
Dry Age-related macular degeneration (AMD) is characterized by the formation of subretinal pigment epithelium (RPE) deposits, as a result of the deregulation in the turnover of extracellular matrix (ECM) molecules, although the mechanism involved remains unclear. Hypertension (HTN) is an important risk factor for AMD and Ang II is the most important hormone associated with HTN. However, the relevance of Ang II receptors and Ang II action on RPE has not been investigated yet. Therefore, the expression and regulation of Ang II receptors as well as the ECM turnover were studied in human RPE. Ang II receptors were expressed and upregulated by Ang II in human RPE. This regulation resulted in functional receptor expression, since increases in [Ca2+]i were observed. Ang II also increased MMP-2 activity and MMP-14 at the mRNA and protein levels. These Ang II effects were abolished by the AT1 receptor antagonist candesartan. In contrast, Ang II decreased type IV collagen via both AT1 and AT2 receptors, suggesting a synergistic effect of the two receptor subtypes. In conclusion, we have confirmed the presence of Ang II receptors in human RPE and their regulation by Ang II as well as the regulation of ECM molecules via Ang II receptors. Our data support the hypothesis that Ang II may exert biological function in RPE through Ang II receptors and that Ang II may deregulate molecules that influence the turnover of ECM in RPE basement membrane suggesting a pathogenic mechanism to explain the link between HTN and AMD.
