Captopril Reduces Retinal Neovascularization in a Mouse Model of ROP

Tadesse, Misrak; Yan, Yun; Yossuck, Panitan; Higgins, Rosemary D.

doi:10.1203/00006450-199904020-00422

Cited by 14 publications

(19 citation statements)

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“…Deficiency of eNOS, either through gene disruption or pharmacologic inhibition, significantly protects the developing retina from oxygen-induced retinopathy (41). ET-1 mRNA expression is also upregulated under the exposure of hypoxia (42), and ET-1 enhances VEGF-induced angiogenic-related effects on endothelial cells in vitro (43). Indeed, the vasoconstrictive response to hyperoxia has been proposed to be ET-1 dependent (44,45).…”

Section: Figurementioning

confidence: 98%

Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization

Kondo¹,

Vicent²,

Suzuma³

et al. 2003

J. Clin. Invest.

178

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Both insulin and IGF-1 have been implicated in control of retinal endothelial cell growth, neovascularization, and diabetic retinopathy. To precisely define the role of insulin and IGF-1 signaling in endothelium in these processes, we have used the oxygen-induced retinopathy model to study mice with a vascular endothelial cell–specific knockout of the insulin receptor (VENIRKO) or IGF-1 receptor (VENIFARKO). Following relative hypoxia, VENIRKO mice show a 57% decrease in retinal neovascularization as compared with controls. This is associated with a blunted rise in VEGF, eNOS, and endothelin-1. By contrast, VENIFARKO mice show only a 34% reduction in neovascularization and a very modest reduction in mediator generation. These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process

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Section: Figurementioning

confidence: 98%

Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization

Kondo¹,

Vicent²,

Suzuma³

et al. 2003

J. Clin. Invest.

178

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“…[1][2][3] Furthermore, many animal studies have suggested strongly that ACE inhibitors and ARBs suppress the retinal pathology including retinal inflammation in STZ-induced diabetic models [17][18][19] and retinal neovascularisation in oxygen-induced retinopathy models. 20,21 Taken together, it is likely that local activation of RAS by the angiotensin II-dependent pathway may be essential to generate the pathological changes in DR. However, some degree of the importance of local activation of RAS by the angiotensin II-independent pathway recently was elucidated.…”

Section: Discussionmentioning

confidence: 99%

Higher levels of prorenin predict development of diabetic retinopathy in patients with type 2 diabetes

Yokota

Nagaoka

Tani

et al. 2011

J Renin Angiotensin Aldosterone Syst

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The aim was to determine whether serum prorenin levels affect the development of diabetic retinopathy (DR) in type 2 diabetes. Baseline serum prorenin levels were measured in 196 patients (85 males, 111 females) with type 2 diabetes without DR using the antibody-activating direct prorenin assay. The fundi were checked regularly. The participants were divided into two groups based on the serum prorenin levels (high and low). We used Kaplan-Meyer analysis to detect differences in the development of DR between the two groups within the same gender. Kaplan-Meyer analysis showed that males with a high serum prorenin level tended to develop DR earlier and more frequently than males with a low prorenin level (p = 0.004 by the log rank test). However, there was no difference in the development of DR between high and low groups in females (p = 0.58). Serum prorenin levels in males with type 2 diabetes could be a new prognostic indicator of the development of DR.

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“…Moreover, ET-1 expression in the retina increased 4.1-fold from P7 to P12 and a 1.9-fold increase from P12 to P17. Overall, there was an 8-fold increase in ET-1 expression from P7 to P17 (Tadesse et al, 2001).…”

mentioning

confidence: 95%

Pleiotropic Effects of YC-1 Selectively Inhibit Pathological Retinal Neovascularization and Promote Physiological Revascularization in a Mouse Model of Oxygen-Induced Retinopathy

DeNiro¹,

Al-Halafi²,

Almohanna³

et al. 2009

Mol Pharmacol

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Vascular endothelial growth factor (VEGF) and inducible nitricoxide synthase (iNOS) have been implicated in ischemia-induced retinal neovascularization. Retinal ischemia has been shown to induce VEGF and iNOS expression. It has been postulated that one of the crucial consequences of iNOS expression in the ischemic retina is the inhibition of angiogenesis. Furthermore, iNOS was shown to be overexpressed in Mü ller cells from patients with diabetic retinopathy. YC-1, a small molecule inhibitor of hypoxia-inducible factor (HIF)-1␣, has been shown to inhibit iNOS expression in various tissue models. Our aim was to assess the pleiotropic effects of YC-1 in an oxygen-induced retinopathy (OIR) mouse model and evaluate its therapeutic potential in HIF-1-and iNOS-mediated retinal pathologies. Dual-injections of YC-1 into the neovascular retinas decreased the total retinopathy score, inhibited vaso-obliteration and pathologic tuft formation, and concomitantly promoted physiological retinal revascularization, compared with dimethyl sulfoxide (DMSO)-treated group. Furthermore, YC-1-treated retinas exhibited a marked increase in immunoreactivities for CD31 and von Willebrand factor and displayed significant inhibition in HIF-1␣ protein expression. Furthermore, YC-1 down-regulated VEGF, erythropoietin, endothelin-1, matrix metalloproteinase-9, and iNOS message and protein levels. When hypoxic Mü ller and neuoroglial cells were treated with YC-1, iNOS mRNA and protein levels were reduced in a dosedependent fashion. We demonstrate that YC-1 inhibits pathological retinal neovascularization by exhibiting antineovascular activities, which impaired ischemia-induced expression of HIF-1 and its downstream angiogenic molecules. Furthermore, YC-1 enhanced physiological revascularization of the retinal vascular plexuses via the inhibition of iNOS mRNA and protein expressions. The pleiotropic effects of YC-1 allude to its possible use as a promising therapeutic iNOS inhibitor candidate for the treatment of retinal neovascularization.Retinal neovascularization (NV) is the major cause of severe vision loss and irreversible blindness in developed countries, affecting people of all ages (Lee et al., 1998). These clinical and pathologic manifestations occur in diabetic retinopathy, retinopathy of prematurity (ROP), age-related macular degeneration and retinal vein occlusion. The early stages of retinopathy result from retinal ischemia as a result of nonperfusion of the retina or a decrease in oxygen tension (Barinapa, 1995). In the late stages, the ischemia-induced pathologic growth of new blood vessels can cause catastrophic loss of vision.

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Captopril Reduces Retinal Neovascularization in a Mouse Model of ROP

Cited by 14 publications

References 0 publications

Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization

Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization

Higher levels of prorenin predict development of diabetic retinopathy in patients with type 2 diabetes

Pleiotropic Effects of YC-1 Selectively Inhibit Pathological Retinal Neovascularization and Promote Physiological Revascularization in a Mouse Model of Oxygen-Induced Retinopathy

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