Does the aqueous humor have a role in mitogen-activated protein kinase (MAPK) intracellular signaling in Glaucoma?

Beit‐Yannai, Elie; Shmulevich, A.

doi:10.1016/j.mehy.2006.05.067

Cited by 18 publications

(18 citation statements)

References 12 publications

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“…Moreover, increased levels of HP-specific IgG antibodies have been found directly in the aqueous humour of glaucomatous patients 15. Recently, it has been proposed that mitogen-activated protein kinases (MAPKs) present in the aqueous humour could be involved in glaucoma pathogenesis;83 mitogen-activated protein kinase networks are involved in the apoptotic process, which is a possible cellular response to oxidative stress 84…”

Section: Discussionmentioning

confidence: 99%

Glaucoma and Helicobacter pylori infection: correlations and controversies

Izzotti

Saccà

Bagnis

et al. 2009

British Journal of Ophthalmology

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A possible association between Helicobacter pylori infection (fig 1) and eye diseases, including Sjogren syndrome, blepharitis, central serous chorioretinopathy and uveitis, has been proposed. Glaucoma is the second leading cause of blindness in the world, after cataracts, and the leading cause of irreversible blindness, but many aspects of its pathogenesis remain unknown. H pylori infection may influence the pathophysiology of glaucoma by releasing various proinflammatory and vasoactive substances, as well as by influencing the apoptotic process, parameters that may also exert their own effects in the induction and/or progression of glaucomatous neuropathy. It is difficult to understand how H pylori infection can be linked to such varied pathologies. Systemic H pylori-induced oxidative damage may be the mechanism which links oxidative stress, H pylori infection and the damage to the trabecula

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Section: Discussionmentioning

confidence: 99%

Glaucoma and Helicobacter pylori infection: correlations and controversies

Izzotti

Saccà

Bagnis

et al. 2009

British Journal of Ophthalmology

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“…that have been linked to glaucoma [43–45] are known to affect the Erk1/2 pathway. [46] Moreover, surgical methods for glaucoma treatment like trabeculectomies are thought to aid in normalization of TM tissue by stimulating secretion of TNFα and restoring TM extracellular matrix through the Erk1/2 pathway. [35] Erk1/2 has also been shown to be directly upregulated as a cellular response to increased IOP[46] in a rabbit[47] and a rat model[48] of elevated IOP.…”

Section: Discussionmentioning

confidence: 99%

“…[46] Moreover, surgical methods for glaucoma treatment like trabeculectomies are thought to aid in normalization of TM tissue by stimulating secretion of TNFα and restoring TM extracellular matrix through the Erk1/2 pathway. [35] Erk1/2 has also been shown to be directly upregulated as a cellular response to increased IOP[46] in a rabbit[47] and a rat model[48] of elevated IOP. Based on these studies, it has been hypothesized that Erk1/2 could be an important target for glaucoma therapeutics.…”

Section: Discussionmentioning

confidence: 99%

ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandil lower intraocular pressure by activating the Erk1/2 signaling pathway

et al. 2017

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Elevated intraocular pressure is the most prevalent and only treatable risk factor for glaucoma, a degenerative disease of the optic nerve. While treatment options to slow disease progression are available, all current therapeutic and surgical treatments have unwanted side effects or limited efficacy, resulting in the need to identify new options. Previous reports from our laboratory have established a novel ocular hypotensive effect of ATP-sensitive potassium channel (KATP) openers including diazoxide (DZ) and nicorandil (NCD). In the current study, we evaluated the role of Erk1/2 signaling pathway in KATP channel opener mediated reduction of intraocular pressure (IOP). Western blot analysis of DZ and NCD treated primary normal trabecular meshwork (NTM) cells, human TM (isolated from perfusion cultures of human anterior segments) and mouse eyes showed increased phosphorylation of Erk1/2 when compared to vehicle treated controls. DZ and NCD mediated pressure reduction (p<0.02) in human anterior segments (n = 7 for DZ, n = 4 for NCD) was abrogated by U0126 (DZ + U0126: -9.7 ± 11.5%, p = 0.11; NCD + U0126: -0.1 ± 11.5%, p = 1.0). In contrast, U0126 had no effect on latanoprostfree acid-induced pressure reduction (-52.5 ± 6.8%, n = 4, p = 0.001). In mice, DZ and NCD reduced IOP (DZ, 14.9 ± 3.8%, NCD, 16.9 ± 2.5%, n = 10, p<0.001), but the pressure reduction was inhibited by U0126 (DZ + U0126, 0.7 ± 3.0%; NCD + U0126, 0.9 ± 2.2%, n = 10, p>0.1). Histologic evaluation of transmission electron micrographs from DZ + U0126 and NCD + U0126 treated eyes revealed no observable morphological changes in the ultrastructure of the conventional outflow pathway. Taken together, the results indicate that the Erk1/2 pathway is necessary for IOP reduction by KATP channel openers DZ and NCD.

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“…Among the known targets of oxidant-mediated signaling is the mitogen-activated protein kinase (MAPK) cascade, which comprises highly conserved serine/threonine kinases, connecting cell surface receptors to regulatory targets in response to various stimuli [20]. The MAPK pathway can be stimulated by a number of factors contributing to the pathophysiology of primary open-angle glaucoma, including different types of mechanical [21]–[23] and oxidative [24] stress.…”

Section: Introductionmentioning

confidence: 99%

Cross-Talk between Ciliary Epithelium and Trabecular Meshwork Cells In-Vitro: A New Insight into Glaucoma

Lerner

Beit‐Yannai

2014

PLoS ONE

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PurposeIt is assumed that the non-pigmented ciliary epithelium plays a role in regulating intraocular pressure via its neuroendocrine activities. To test this hypothesis, we investigated the effect on a human trabecular meshwork (TM) cell line (NTM) of co-culture with a human non-pigmented ciliary epithelium cell line (ODM-2).MethodsThe cellular cross-talk between ODM-2 and NTM cells was studied in a co-culture system in which the two cell types were co-cultured for 5 to 60min or 2, 4 and 8h and then removed from the co-culture and analyzed. Analyses of the ERK and p38 mitogen-activated protein kinase (MAPK) pathways and of the activity of TM phosphatases and matrix metalloproteins (MMPs) were performed. Acid and alkaline phosphatase activity was determined by the DiFMUP (6, 8-difluoro-4-methylumbelliferyl phosphate) assay. MMP levels were determined by gelatin zymography.ResultsExposure of NTM cells to ODM-2 cells led to the activation of the MAPK signal transduction pathways in NTM cells within 5min of co-culture. Phosphorylation of ERK1/ERK2 and p38 peaked at 10 and 15min and then decreased over time. Interaction between ODM-2 and NTM cells promoted the expression of MMP-9 in the NTM cells after 4h of co-culture.ConclusionsOur findings provide support for the hypothesis that crosstalk does indeed take place between ODM-2 and NTM cells. Future studies should be designed to determine the relationship between the MMP system, MAPK kinases and phosphatases. Manipulation of these signaling molecules and the related NTM signal transduction pathways may provide targets for developing improved treatments for glaucoma.

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Does the aqueous humor have a role in mitogen-activated protein kinase (MAPK) intracellular signaling in Glaucoma?

Cited by 18 publications

References 12 publications

Glaucoma and Helicobacter pylori infection: correlations and controversies

Glaucoma and Helicobacter pylori infection: correlations and controversies

ATP-sensitive potassium (KATP) channel openers diazoxide and nicorandil lower intraocular pressure by activating the Erk1/2 signaling pathway

Cross-Talk between Ciliary Epithelium and Trabecular Meshwork Cells In-Vitro: A New Insight into Glaucoma

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