Natriuretic Peptide Receptors, NPR-A and NPR-B, in Cultured Rabbit Retinal Pigment Epithelium Cells

Fujiseki, Yoshito; Omori, Kyoko; Omori, Koichiro; Mikami, Yoshito; Suzukawa, Junko; Okugawa, Gaku; Uyama, M; Inagaki, Chiyoko

doi:10.1254/jjp.79.359

Cited by 14 publications

(6 citation statements)

References 35 publications

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“…ANP blocks the VEGF response, if given apically but not basolaterally, which indicates an apical localization of ANP receptors in the RPE cells. Previous studies have shown that NP receptors are present in the retina 13 and in RPE cells 24 ; however, direct evidence for exact localization of the receptors in the retina or RPE cells does not exist.…”

Section: Discussionmentioning

confidence: 94%

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

Lara-Castillo

Zandi

Nakao

et al. 2009

The American Journal of Pathology

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Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however , its role in vascular leakage and angiogenesis is unknown. In vitro , retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 mol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGFinduced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP's effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP's TEER response was concentration but not time dependent. In vivo, ANP significantly reduced VEGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum , ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role , such as age-related macular degeneration or diabetic retinopathy.

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Section: Discussionmentioning

confidence: 94%

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

Lara-Castillo

Zandi

Nakao

et al. 2009

The American Journal of Pathology

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“…Also in the RPE cell layer of the human retina strong ANP immunolabeling has previously been shown [26] . In addition, mRNA of NPR-A and NPR-B, both ANP receptors, has been demonstrated in cultured rabbit RPE cells [9] . Histochemical and molecular cloning studies have also revealed the presence of the NPR-A and NPR-B in the human and turtle retina [7,10,24] .…”

Section: Discussionmentioning

confidence: 99%

Cyclic GMP Synthesis by Human Retinal Pigment Epithelial Cells Is Mainly Mediated via the Particulate Guanylyl Cyclase Pathway

et al. 2006

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Background/Aims: Cyclic 3′,5′-guanosine monophosphate (cGMP), a central molecule in the phototransduction cascade, is also involved in a number of other physiological processes in the retina, like stimulating the absorption of subretinal fluid by activating the retinal pigment epithelium (RPE) cell pump. The aim of this study was to quantify cGMP synthesis by RPE cells and to investigate the role of two separate enzymatic pathways (soluble versus particulate guanylyl cyclase) in its production. Methods: cGMP expression was evaluated by immunochemistry and radioimmunoassay following culture of the D407 RPE cell line in the presence of a nonselective phosphodiesterase inhibitor (IBMX), in combination with the particulate guanylyl cyclase stimulator atrial natriuretic peptide (ANP) or the soluble guanylyl cyclase stimulator sodium nitroprusside (SNP). Results: Stimulation of the particulate guanylyl cyclase in RPE cells with ANP resulted in high intra- and extracellular cGMP levels. Stimulation of the soluble guanylyl cyclase by SNP resulted in a slight elevation of cGMP levels compared to controls. Conclusions: These results show that cultured human RPE cells are capable of producing cGMP and that most cGMP is generated following stimulation of the particulate guanylyl cyclase pathway.

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“…In the eye, studies have shown that NP receptors are present in the mammalian neural retina (Rollin et al, 2004) and RPE (Fujiseki et al, 1999), and the activation of these receptors can influence vascular endothelial growth factor-induced permeability changes in the RPE (Ablonczy and Crosson, 2007;LaraCastillo et al, 2009). However, the receptor subtype responsible for this response has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

C-Type Natriuretic Peptide Protects the Retinal Pigment Epithelium against Advanced Glycation End Product–Induced Barrier Dysfunction

Dahrouj

Alsarraf

Liu

et al. 2012

J Pharmacol Exp Ther

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In diabetic retinopathy, vision loss is usually secondary to macular edema, which is thought to depend on the functional integrity of the blood-retina barrier. The levels of advanced glycation end products in the vitreous correlate with the progression of diabetic retinopathy. Natriuretic peptides (NP) are expressed in the eye and their receptors are present in the retinal pigment epithelium (RPE). Here, we investigated the effect of glycated-albumin (Glyc-alb), an advanced glycation end product model, on RPE-barrier function and the ability of NP to suppress this response. Transepithelial electrical resistance (TEER) measurements were used to assess the barrier function of ARPE-19 and human fetal RPE (hfRPE) monolayers. The monolayers were treated with 0

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Natriuretic Peptide Receptors, NPR-A and NPR-B, in Cultured Rabbit Retinal Pigment Epithelium Cells

Cited by 14 publications

References 35 publications

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

Cyclic GMP Synthesis by Human Retinal Pigment Epithelial Cells Is Mainly Mediated via the Particulate Guanylyl Cyclase Pathway

C-Type Natriuretic Peptide Protects the Retinal Pigment Epithelium against Advanced Glycation End Product–Induced Barrier Dysfunction

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