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Query: UMLS:C0595921 (
intraocular pressure
)
11,750
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Retinal ganglion cells process the visual signal and transmit it along their axons in the optic nerve to the brain. Molecular, immunohistochemical, and functional analyses indicate that the majority of retinal ganglion cells express the ionotropic P2X(7) receptor. Stimulation of the receptor can lead to a rise in intracellular calcium and cell death, although death does not involve the opening of a large diameter pore.
Adenosine
acting at A(3) receptors can attenuate the rise in calcium and death accompanying P2X(7) receptor activation, suggesting that dephosphorylation of ATP into adenosine is neuroprotective and that the balance of extracellular purines can influence neuronal survival. Increased
intraocular pressure
can lead to release of excessive extracellular ATP in the retina and damage ganglion cells by acting on P2X(7) receptors, implicating a role for the receptor in the loss of ganglion cell activity in glaucoma. In summary, the activation of P2X(7) receptors has both physiologic and pathophysiologic implications for ganglion cell function. These characteristics may also provide an insight into the contributions the P2X(7) receptor makes to neurons elsewhere.
...
PMID:The P2X(7) receptor in retinal ganglion cells: A neuronal model of pressure-induced damage and protection by a shifting purinergic balance. 1924 Nov 45
Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly "tuned," can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P(1),P(4)-diadenosine tetraphosphate (Ap4A), and P(1),P(5)-diadenosine pentaphosphate (Ap5A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes.
Adenosine
receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (CF101) have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large
intraocular pressure
increases) can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.
...
PMID:Purinergic receptors in ocular inflammation. 2513 32
Among candidate neuroprotective agents, adenosine is thought to be a possible treatment for central nervous system disorders.
Adenosine
elicits biological effects through four G protein-coupled receptors (A
1
, A
2A
, A
2B
, and A
3
). The A
2A
and A
2B
receptors stimulate adenylyl cyclase (AC) and increase cyclic adenosine monophosphate (cAMP) levels, whereas A
1
and A
3
receptors inhibit AC and decrease cAMP levels. Several studies have investigated the effects of adenosine receptors (AdoRs) in glaucoma, because modulation of A
1
, A
2A
, or A
3
receptor regulates
intraocular pressure
. In addition, AdoR-related phenomena may induce neuroprotective effects in retinal neurons. Notably, A
1
, A
2A
, and A
3
receptor agonists reportedly inhibit retinal ganglion cell (RGC) death in in vitro and in vivo glaucoma models. However, there is limited knowledge of the effects of AdoR activation on neurite outgrowth or the regeneration of RGCs. In this report, we described the role of an AdoR subtype in neurite outgrowth and RGC axonal regeneration. The distribution of AdoRs in the retina was evaluated by immunohistochemical analysis. Using primary cultured rat RGCs in vitro and an optic nerve crush model in vivo, neurite elongation was evaluated after stimulation by the following AdoR agonists: CHA, an A
1
receptor agonist; CGS21680, an A
2A
receptor agonist; BAY60-6583, an A
2B
receptor agonist; and 2-Cl-IB-MECA, an A
3
receptor agonist. To determine the mechanism of neurite promotion, the candidate molecules of signal transduction associated with the neurite elongation of AdoRs were evaluated by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis, respectively. All four AdoRs (A
1
, A
2A
, A
2B
, and A
3
) were present in the inner retinal layers. Among the agonists for AdoR, only 2-Cl-IB-MECA significantly promoted neurite outgrowth in primary cultured RGCs. Signaling pathway analyses showed that 2-Cl-IB-MECA caused upregulated phosphorylation of Akt in cultured RGCs. Additionally, LY294002, an inhibitor of Akt, suppressed the neurite-promoting effects of the A
3
receptor agonist in RGCs. Moreover, 2-Cl-IB-MECA increased the number of regenerating axons in the optic nerve crush model. Taken together, these data indicate that activation of the A
3
receptor, not the A
1
or A
2
receptors, promotes in vitro and in vivo neurite outgrowth during the regeneration of rat RGCs, which is caused by the activation of an Akt-dependent signaling pathway. Therefore, AdoR activation may be a promising candidate for the development of novel regenerative modalities for glaucoma and other optic neuropathies.
...
PMID:Stimulation of the adenosine A3 receptor, not the A1 or A2 receptors, promote neurite outgrowth of retinal ganglion cells. 2948 64
Glaucoma is a progressive chronic retinal degenerative disease and a leading cause of global irreversible blindness. This disease is characterized by optic nerve damage and retinal ganglion cell (RGC) death. The current treatments available target the lowering of
intraocular pressure
(
IOP
), the main risk factor for disease onset and development. However, in some patients, vision loss progresses despite successful
IOP
control, indicating that new and effective treatments are needed, such as those targeting the neuroprotection of RGCs.
Adenosine
A
3
receptor (A
3
R) activation confers protection to RGCs following an excitotoxic stimulus. In this work, we investigated whether the activation of A
3
R could also afford protection to RGCs in the laser-induced ocular hypertension (OHT) model, a well-characterized animal model of glaucoma. The intravitreal injection of 2-Cl-IB-MECA, a selective A
3
R agonist, abolished the alterations induced by OHT in the negative and positive components of scotopic threshold response (STR) without changing a- and b-wave amplitudes both in scotopic and photopic conditions. Moreover, the treatment of OHT eyes with the A
3
R agonist promoted the survival of RGCs, attenuated the impairment in retrograde axonal transport, and improved the structure of the optic nerve. Taking into consideration the beneficial effects afforded by 2-Cl-IB-MECA, we can envisage that A
3
R activation can be considered a good therapeutic strategy to protect RGCs from glaucomatous damage.
...
PMID:Activation of adenosine A
3
receptor protects retinal ganglion cells from degeneration induced by ocular hypertension. 3246 78
Glaucoma is a progressive chronic retinal degenerative disease and a leading cause of global irreversible blindness, characterized by optic nerve damage and retinal ganglion cell (RGC) death. Elevated
intraocular pressure
(
IOP
) is a main risk factor of glaucoma. Neuroinflammation plays an important role in glaucoma. We have been demonstrating that elevated pressure triggers microglia reactivity that contribute to the loss of RGCs.
Adenosine
, acting on adenosine receptors, is a crucial modulator of microglia phenotype. Microglia express all adenosine receptors. Previously, we demonstrated that the activation of adenosine A
3
receptor (A
3
R) affords protection to the retina, including RGCs, unveiling the possibility for a new strategy for glaucoma treatment. Since microglial cells express A
3
R, we now studied the ability of a selective A
3
R agonist (2-Cl-IB-MECA) in controlling microglia reactivity induced by elevated hydrostatic pressure (EHP), used to mimic elevated
IOP
. The activation of A
3
R reduced EHP-induced inducible nitric oxide synthase (iNOS) expression, microglia migration and phagocytosis in BV-2 cells. In retinal microglia, proliferation and phagocytosis elicited by EHP were also decreased by A
3
R activation. This work demonstrates that 2-Cl-IB-MECA, the selective agonist of A
3
R, is able to hinder microglia reactivity, suggesting that A
3
R agonists could afford protection against glaucomatous degeneration through the control of neuroinflammation.
...
PMID:Activation of Adenosine A
3
Receptor Inhibits Microglia Reactivity Elicited by Elevated Pressure. 3300 35
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