Purchase this article with an account.
Yanhong Wei, Junsong Gong, Rajesh Thimmulappa, shyam biswal, Elia J Duh; Nrf2 promotes retinal revascularization and decreases pathologic angiogenesis in oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3402.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Nrf2 is an important regulator of the antioxidant response and also has anti-inflammatory effects. We have previously demonstrated that Nrf2 has a cytoprotective role in retinal ischemia-reperfusion injury and diabetic retinopathy. We also found that Nrf2 promotes vascular sprouting and branching during retinal vascular development. The objective of this study was to gain insights into the possible role of Nrf2 in oxygen-induced retinopathy (OIR).
For OIR studies, mice were subjected to hyperoxia from postnatal day 7 (P7) to 12, followed by return to room air. Retinal flatmounts were prepared at P12 and P17, and analyzed for avascular retinal area as well as retinal neovascularization. For these studies, we employed global Nrf2 knockout mice (Nrf2-/-) and corresponding wild-type control mice. Hypoxyprobe was used to detect hypoxic regions in the retina at P17. Blood-retina barrier function was assessed by measuring retinal levels of the systemically administered tracer, [3H] mannitol. The effect of pharmacologic activation of Nrf2 was evaluated by administration of CDDO-Im, a synthetic triterpenoid.
At P12, there was no difference in the extent of retinal vaso-obliteration between Nrf2 knockout and wild-type mice. However, Nrf2 knockout mice exhibited significantly increased avascular retina and pathologic retinal neovascularization at P17 compared to wild-type. Marked increase in hypoxic retinal region and vascular leakage were observed in Nrf2 knockout mice at P17. Nuclear translocation of Nrf2 was increased in mouse retina in OIR, indicationg Nrf2 activation. Further activation Nrf2 by CDDO-Im significantly improved retinal revascularization and reduced pathologic neovascularization.<br />
These studies suggest that Nrf2 could play an important role in oxygen-induced retinopathy by promoting revascularization of avascular retina. Nrf2 could therefore be a therapeutic target for ischemic retinopathies.
This PDF is available to Subscribers Only