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

Diederen, Roselie M.H.; Heij, Ellen C. La; Ittersum, Marjanne Markerink‐van; Kijlstra, Aize; Hendrikse, Fred; Vente, Jan de

doi:10.1159/000098015

Cited by 5 publications

(3 citation statements)

References 39 publications

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“…In the neural retina, we found that the cluster linked with purine/pyrimidine metabolism has the highest effect. As a confirmation of the validity of our finding, we show (Figure 1E) that the measurements of known metabolites like cGMP (Diederen et al, 2007;Ferrendelli and De Vries, 1983), flavins (Sinha et al, 2018), gamma-aminobutyric acid (GABA) (Bringmann et al, 2013;Cheng et al, 2013), and retinoids (Kuksa et al, 2003) are in agreement with previous data.…”

Section: Introductionsupporting

confidence: 91%

The Symbiotic Relationship between the Neural Retina and Retinal Pigment Epithelium Is Supported by Utilizing Differential Metabolic Pathways

2020

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The neural retina and retinal pigment epithelium (RPE) maintain a symbiotic metabolic relationship, disruption of which leads to debilitating vision loss. The current study was undertaken to identify the differences in the steady-state metabolite levels and the pathways functioning between bona fide neural retina and RPE. Global metabolomics and cluster analyses identified 650 metabolites differentially modulated between the murine neural retina and RPE. Of these, 387 and 163 were higher in the RPE and the neural retina, respectively. Further analysis coupled with transcript and protein level investigations revealed that under normal physiological conditions, the RPE utilizes the pentose phosphate (>3-fold in RPE), serine (>10-fold in RPE), and sphingomyelin biosynthesis (>5-fold in RPE) pathways. Conversely, the neural retina relied mostly on glycolysis. These results show how the RPE and the neural retina have acquired an efficient, complementary and metabolically diverse symbiotic niche to support each other's distinct functions.

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Section: Introductionsupporting

confidence: 91%

The Symbiotic Relationship between the Neural Retina and Retinal Pigment Epithelium Is Supported by Utilizing Differential Metabolic Pathways

2020

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“…1,2 ANP significantly increases intracellular cGMP levels in human RPE, whereas the nitric oxide donor Nanitroprusside (an activator of soluble guanylyl cyclase) is less effective. 30,31 In the rabbit RPE in culture, the application of ANP increases chloride uptake, 32 an effect that is reduced by inhibition of PKG by KT5823. Recent investigation of interferon-gamma signaling via cyclic nucleotides cGMP and cAMP in human RPE demonstrated an increase in fluid transport that was reduced in the presence of either PKA inhibitor H-89 or inhibition of CFTR at the basal membrane.…”

Section: Discussionmentioning

confidence: 99%

Stimulation of Aquaporin-Mediated Fluid Transport by Cyclic GMP in Human Retinal Pigment Epithelium In Vitro

Baetz

Stamer

Yool

2012

Invest. Ophthalmol. Vis. Sci.

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“…All three natriuretic peptides have been observed in human RPE cells [10] . Recently we showed that human RPE cells are capable of producing cGMP and that most cGMP is generated following stimulation of the pGC pathway [11] .…”

Section: Introductionmentioning

confidence: 99%

Two Autocrine Pathways to Regulate Cyclic GMP Synthesis in Cultured Human Retinal Pigment Epithelial Cells

et al. 2008

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Aim: To investigate the role of two separate enzymatic pathways [soluble (sGC) vs. particulate (pGC) guanylyl cyclase] in the synthesis of cyclic GMP (cGMP) in cultured human retinal pigment epithelial (RPE) cells. Methods: cGMP accumulation was evaluated by quantitative analysis of cGMP immunoreactivity. RPE cells were also stained for inducible nitric oxide synthase (iNOS), ANP and β₁- and α₂-subunits of sGC. Results: We showed nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase activity and iNOS immunoreactivity in RPE cells. Incubation of the cells in the presence of 1 mM IBMX to inhibit phosphodiesterase activity, and the simultaneous inhibition of NOS activity with L-NAME suggested the involvement of sGC in maintaining a low level of cGMP in the RPE cells. The involvement of sGC was further supported by detection of the β₁- and α₂-subunits of sGC. Incubation of the cells in the presence of atrial natriuretic peptide (ANP) to stimulate pGC strongly increased cGMP immunoreactivity. We also demonstrated the presence of ANP in all RPE cells. Conclusion: Cultured human RPE cells are capable of producing cGMP after stimulation of sGC or pGC. The presence of iNOS and ANP in all cells suggests two different autocrine pathways of stimulating cGMP production in these cells. The possible role of cGMP in the regulation iNOS gene expression and in the regulation of ANP is discussed.

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

Cited by 5 publications

References 39 publications

The Symbiotic Relationship between the Neural Retina and Retinal Pigment Epithelium Is Supported by Utilizing Differential Metabolic Pathways

The Symbiotic Relationship between the Neural Retina and Retinal Pigment Epithelium Is Supported by Utilizing Differential Metabolic Pathways

Stimulation of Aquaporin-Mediated Fluid Transport by Cyclic GMP in Human Retinal Pigment Epithelium In Vitro

Two Autocrine Pathways to Regulate Cyclic GMP Synthesis in Cultured Human Retinal Pigment Epithelial Cells

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