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Targeting MAPK Signaling in Age-Related Macular Degeneration.

Kyosseva SV - Ophthalmol Eye Dis (2016)

Bottom Line: AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors.This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD.The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

ABSTRACT
Age-related macular degeneration (AMD) is a major cause of irreversible blindness affecting elderly people in the world. AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in the pathogenesis of AMD. The mitogen-activated protein kinase (MAPK) signaling pathways are activated by diverse extracellular stimuli, including growth factors, mitogens, hormones, cytokines, and different cellular stressors such as oxidative stress. They regulate cell proliferation, differentiation, survival, and apoptosis. This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD. The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease.

No MeSH data available.


Related in: MedlinePlus

Schematic presentation depicting the role of ERK, JNK, and p38 in dry and wet AMD.
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Related In: Results  -  Collection


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f2-oed-8-2016-023: Schematic presentation depicting the role of ERK, JNK, and p38 in dry and wet AMD.

Mentions: There is a crosstalk between MAPK signaling and several different pathways, such as VEGF, inflammasome, autophagy, and others. VEGF is known to be the major angiogenic factor involved in AMD.39–43 MAPK pathways play an essential role in modulating VEGF. It has been demonstrated that constitutive activation of ERK1/2 leads to increased VEGF expression,85 and overexpression of p38 and JNK leads to elevated VEGF expression.86 Inflammasomes play a central role in innate immune system. ROS serves as an important inflammasome signal that activates MAPK signaling.87 It has been shown that dysregulation of inflammasome plays a role in various pathological conditions including AMD.88 It was reported that NLRP3 inflammasome activation by drusen induces interleukin-18 (IL-18) secretion, which, in turn downregulates VEGF, thus reducing the excessive neoangiogenesis associated with AMD.89 Zhang et al demonstrated that the cytokine IL-17A induced the activation of ERK1/2 and p38 MAPK in RPE cells.90Figure 2 shows a proposed model of MAPK signaling that leads to AMD.


Targeting MAPK Signaling in Age-Related Macular Degeneration.

Kyosseva SV - Ophthalmol Eye Dis (2016)

Schematic presentation depicting the role of ERK, JNK, and p38 in dry and wet AMD.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4920203&req=5

f2-oed-8-2016-023: Schematic presentation depicting the role of ERK, JNK, and p38 in dry and wet AMD.
Mentions: There is a crosstalk between MAPK signaling and several different pathways, such as VEGF, inflammasome, autophagy, and others. VEGF is known to be the major angiogenic factor involved in AMD.39–43 MAPK pathways play an essential role in modulating VEGF. It has been demonstrated that constitutive activation of ERK1/2 leads to increased VEGF expression,85 and overexpression of p38 and JNK leads to elevated VEGF expression.86 Inflammasomes play a central role in innate immune system. ROS serves as an important inflammasome signal that activates MAPK signaling.87 It has been shown that dysregulation of inflammasome plays a role in various pathological conditions including AMD.88 It was reported that NLRP3 inflammasome activation by drusen induces interleukin-18 (IL-18) secretion, which, in turn downregulates VEGF, thus reducing the excessive neoangiogenesis associated with AMD.89 Zhang et al demonstrated that the cytokine IL-17A induced the activation of ERK1/2 and p38 MAPK in RPE cells.90Figure 2 shows a proposed model of MAPK signaling that leads to AMD.

Bottom Line: AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors.This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD.The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.

ABSTRACT
Age-related macular degeneration (AMD) is a major cause of irreversible blindness affecting elderly people in the world. AMD is a complex multifactorial disease associated with demographic, genetics, and environmental risk factors. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in the pathogenesis of AMD. The mitogen-activated protein kinase (MAPK) signaling pathways are activated by diverse extracellular stimuli, including growth factors, mitogens, hormones, cytokines, and different cellular stressors such as oxidative stress. They regulate cell proliferation, differentiation, survival, and apoptosis. This review addresses the novel findings from human and animal studies on the relationship of MAPK signaling with AMD. The use of specific MAPK inhibitors may represent a potential therapeutic target for the treatment of this debilitating eye disease.

No MeSH data available.


Related in: MedlinePlus