Synthesis of leukotrienes in frog retina and retinal pigment epithelium

Bazán, Nicolás G.; Bazán, Haydee E. P.; Birkle, Dale L.; Rossowska, M

doi:10.1002/jnr.490180412

Cited by 18 publications

(4 citation statements)

References 23 publications

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“…Production of cysLTs in whole‐retina preparations appears to be species specific. For example, frog retinas can produce LTC 4 following Ca 2+ ‐ionophore stimulation (44), and rat retinas produce LTB 4 in response to light and trauma (45), whereas cultured bovine pericytes are able to produce cysLTs only in the presence of polymorphonuclear cells, as they produce and donate the LTA 4 (17). Isolated adult mouse retinas require the addition of LTA 4 in order to synthesize LTB 4 , as the tissue in those studies was apparently devoid of 5‐LOX mRNA (15).…”

Section: Discussionmentioning

confidence: 99%

The cysteinyl leukotriene 2 receptor mediates retinal edema and pathological neovascularization in a murine model of oxygen‐induced retinopathy

Barajas-Espinosa

Dong

et al. 2011

FASEB j.

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Leukotrienes have been implicated in the pathogenesis of degenerative diabetic retinopathy, with research focusing primarily on leukotriene B(4), with little attention devoted to the cysteinyl leukotrienes (cysLTs), which act through cysLT receptors (CysLT(1)R and CysLT(2)R). We demonstrate here the presence of CysLT(2)R in pericytes and endothelial cells of superficial retinal vasculature using an indirect assay by assessment of β-galactosidase expression in CysLT(2)R-knockout (KO) mice. Retinal damage was induced in KO and wild-type (WT) mice using an established oxygen-induced retinopathy (OIR) model. CysLT(2)R expression following OIR was intensely up-regulated compared to sham-treated controls. Staining with Griffonia simplicifolia lectin revealed enhanced tissue damage (as assessed by vasoobliteration/vasoproliferation) in KO mice compared to WT controls, yet the opposite was true with respect to retinal edema. However, vascular endothelial growth factor receptor 1 (VEGFR1) transcripts were increased by OIR similarly with respect to genotype. Intravitreal application of exogenous cysLTs elicited greater vasculature leakage (assessed ex vivo) in eyes from WT mice compared to KO mice. While mRNA encoding enzymes for various components of the leukotriene cascade were detected in sham- and OIR-treated retinas, only prostaglandins and hydroxyeicosatetraenoic acids, but not leukotrienes, were detected in A23187-treated retina preparations. Together, these results implicate the CysLT(2)R in the progression of ischemic retinopathy.

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Section: Discussionmentioning

confidence: 99%

The cysteinyl leukotriene 2 receptor mediates retinal edema and pathological neovascularization in a murine model of oxygen‐induced retinopathy

Barajas-Espinosa

Dong

et al. 2011

FASEB j.

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“…Thus, a very specific free DHA pool may be the precursor for NPD1. Arachidonic acid is also an active precursor of several bioactive lipids, including prostaglandins and lipoxygenase products, and they have been correlated with photoreceptor phagocytosis (31,32). Because arachidonic acid is released under the present experimental conditions (data not shown), it was therefore of interest to explore some of the arachidonic acid cascade members.…”

Section: Pos Phagocytosis Selectively Attenuates Oxidative Stress-indmentioning

confidence: 92%

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

Mukherjee

Marcheselli

Vaccari

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

100

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Photoreceptor cell (rods and cones) renewal is accompanied by intermittent shedding of the distal tips of the outer segment followed by their phagocytosis in the retinal pigment epithelial (RPE) cells. This renewal is essential for vision, and it is thought that it fosters survival of photoreceptors and of RPE cells. However, no specific survival messenger/mediators have as yet been identified. We show here that photoreceptor outer segment (POS) phagocytosis markedly attenuates oxidative stress-induced apoptosis in ARPE-19 cells in culture. This phenomenon does not seem to be a generalized outcome of phagocytosis because nonbiological (polystyrene microsphere) phagocytosis did not elicit protection. The free docosahexaenoic acid (DHA) pool size and neuroprotectin D1 (NPD1) content increased during POS phagocytosis but not during microspheres phagocytosis. We have also explored other lipid mediators [lipoxin A4 and 15(S)-and 12(S)-hydroxyeicosatetraenoic acids] under these conditions and found them unchanged upon POS phagocytosis. Moreover, oxidative stress challenge to RPE cells undergoing POS phagocytosis further increased DHA and NPD1 content. Under these conditions, NPD1 was found within the RPE cells as well as in the culture medium, suggesting autocrine and paracrine bioactivity. Furthermore, using deuterium-labeled DHA, we show that as the availability of free DHA increases during oxidative stress, NPD1 synthesis is augmented in ARPE-19 cells. Our data suggest a distinct signaling that promotes survival of photoreceptor and RPE cells by enhancing the synthesis of NPD1 during phagocytosis. Taken together, NPD1 may be a mediator that promotes homeostatic regulation of cell integrity during photoreceptor cell renewal. docosahexaenoic acid ͉ polystyrene microspheres ͉ retinal pigment epithelial cells ͉ survival ͉ omega-3 fatty acids

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“…AA is also a precursor of bioactive lipids, including prostaglandins and lipoxygenase products, which have been correlated with photoreceptor phagocytosis (46, 47). That AA is released under the present experimental conditions (data not shown), led us to explore some of the AA cascade members.…”

Section: Photoreceptor Cells and Retinal Pigment Epithelial Cellsmentioning

confidence: 99%

Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection

Bazán

2009

Prostaglandins, Leukotrienes and Essential Fatty Acids

154

102

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Deficiency in docosahexaenoic acid (DHA) is associated with impaired visual and neurological postnatal development, cognitive decline, macular degeneration, and other neurodegenerative diseases. DHA is an omega-3 polyunsaturated fatty acyl chain concentrated in phospholipids of brain and retina, with photoreceptor cells displaying the highest content of DHA of all cell membranes. The identification and characterization of neuroprotectin D1 (NPD1, 10R, 17S-dihydroxydocosa-4Z, 7Z, 11E, 13E, 15Z, 19Z-hexaenoic acid) contributes to understanding the biological significance of DHA. In oxidative stress-challenged human retinal pigment epithelial (RPE) cells, human brain cells, or rat brains undergoing ischemia-reperfusion, NPD1 synthesis is enhanced as a response for sustaining homeostasis. Thus, neurotrophins, Aβ peptide 42 (Aβ42), calcium ionophore A23187, interleukin (IL)-1 β, or DHA supply enhances NPD1 synthesis. NPD1, in turn, up-regulates the anti-apoptotic proteins of the Bcl-2 family and decreases the expression of pro-apoptotic Bcl-2 family members. Moreover, NPD1 inhibits IL-1 β-stimulated expression of cyclooxygenase-2 (COX-2). Because both RPE and photoreceptors are damaged and then die in retinal degenerations, elucidating how NPD1 signaling contributes to retinal cell survival may lead to a new understanding of disease mechanisms. In human neural cells, DHA attenuates amyloid-β (Aβ) secretion, resulting in concomitant formation of NPD1. NPD1 was found to be reduced in the Alzheimer's disease (AD) CA1 hippocampal region, but not in other areas of the brain. The expression of key enzymes for NPD1 biosynthesis, cytosolic phospholipase A 2 (cPLA 2 ), and 15-lipoxygenase (15-LOX) was found altered in the AD hippocampal CA1 region. NPD1 repressed Aβ42-triggered activation of proinflammatory genes and upregulated the anti-apoptotic genes encoding Bcl-2, Bcl-xl, and Bfl-1(A1) in human brain cells in culture. Overall, these results support the concept that NPD1 promotes brain and retina cell survival via the induction of anti-apoptotic and neuroprotective gene-expression programs that suppress Aβ42-induced neurotoxicity and other forms of cell injury, which in turn fosters homeostasis during development in aging, as well as during the initiation and progression of neurodegenerative diseases.

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Synthesis of leukotrienes in frog retina and retinal pigment epithelium

Cited by 18 publications

References 23 publications

The cysteinyl leukotriene 2 receptor mediates retinal edema and pathological neovascularization in a murine model of oxygen‐induced retinopathy

The cysteinyl leukotriene 2 receptor mediates retinal edema and pathological neovascularization in a murine model of oxygen‐induced retinopathy

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

Cellular and molecular events mediated by docosahexaenoic acid-derived neuroprotectin D1 signaling in photoreceptor cell survival and brain protection

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