Effect of P2X7 Receptor Activation on the Retinal Blood Velocity of Diabetic Rabbits

Sugiyama, Tetsuya; Oku, Hidehiro; Komori, Asako; Ikeda, Tsunehiko

doi:10.1001/archopht.124.8.1143

Cited by 24 publications

(16 citation statements)

References 28 publications

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“…ATP acts as a vasoactive molecule regulating the function of the pericytes located in rat (Kawamura et al, 2003) and rabbit (Sugiyama et al, 2006) retinal microvessels. ATP modifies ionic currents, increases Ca 21 levels, and causes contraction of pericytes (Kawamura et al, 2003).…”

Section: Function and Therapeutic Potential Of Nucleotides In Eyementioning

confidence: 99%

“…Diabetic retinal microvessels exhibited more pericyte vulnerability to the lethal effect of P2X7 receptor activation (Kawamura et al, 2003;Sugiyama et al, 2006). Low BzATP concentrations (#100 mM), nonlethal for normal retina, triggered pericyte apoptosis through the P2X7 receptor in diabetic retinal microvasculature (Sugiyama et al, 2004).…”

Section: Function and Therapeutic Potential Of Nucleotides In Eyementioning

confidence: 99%

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Nucleotides in the Eye: Focus on Functional Aspects and Therapeutic Perspectives

Guzmán-Aránguez

Santano

Martín-Gil

et al. 2013

J Pharmacol Exp Ther

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The presence and activity of nucleotides and dinucleotides in the physiology of most, if not all, organisms, from bacteria to humans, have been recognized by the scientific community, and the eye is no exception. Nucleotides in the dynamic fluids interact with many ocular structures, such as the tears and aqueous humor. Moreover, high concentrations of nucleotides in these secretions may reflect disease states such as dry eye and glaucoma. Apart from the nucleotide concentration in these fluids, P2 purinergic receptors have been described on the ocular surface (cornea and conjunctiva), anterior pole (ciliary body, trabecular meshwork), and posterior pole (retina). P2X and P2Y purinergic receptors are essential in maintaining the homeostasis of ocular processes, such as tear secretion, aqueous humor production, or retinal modulation. When they are functioning properly, they allow the eye to do its job (to see), but in some cases, a lack or an excess of nucleotides or a malfunction in the corresponding purinergic receptors leads to disease. This Perspective is focused on the nucleotides and dinucleotides and the P2 purinergic receptors in the eye and how they contribute to normal and disease states. We also emphasize the action of nucleotides and their receptors and antagonists as potential therapeutic agents.

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Section: Function and Therapeutic Potential Of Nucleotides In Eyementioning

confidence: 99%

Section: Function and Therapeutic Potential Of Nucleotides In Eyementioning

confidence: 99%

Nucleotides in the Eye: Focus on Functional Aspects and Therapeutic Perspectives

Guzmán-Aránguez

Santano

Martín-Gil

et al. 2013

J Pharmacol Exp Ther

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“…Purinergic chemical transmission was suggested to be involved in apoptosis of photoreceptors and ganglion cells, 2,3,6,29) volume regulation, 30,31) and contraction of pericytes in retinal microvessels. 32,33) Due to technical limitations in the present study, we could not examine whether vesicular ATP release is also impaired in the retinal cells of VNUT −/− mice. Further studies using VNUT −/− mice will be helpful to elucidate the roles of VNUT or vesicular ATP release in the pathophysiology of the retina.…”

Section: Discussionmentioning

confidence: 92%

Expression of Vesicular Nucleotide Transporter in the Mouse Retina

Moriyama

Hiasa

2016

Biological & Pharmaceutical Bulletin

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Vesicular nucleotide transporter (VNUT) is a membrane protein that is responsible for vesicular storage and subsequent vesicular release of nucleotides, such as ATP, and plays an essential role in purinergic chemical transmission. In the present study, we investigated whether VNUT is present in the rodent retina to define the site(s) of vesicular ATP release. In the mouse retina, reverse transcription polymerase chain reaction (RT-PCR) and immunological analyses using specific anti-VNUT antibodies indicated that VNUT is expressed as a polypeptide with an apparent molecular mass of 59 kDa. VNUT is widely distributed throughout the inner and outer retinal layers, particularly in the outer segment of photoreceptors, outer plexiform layer, inner plexiform layer, and ganglion cell layer. VNUT is colocalized with vesicular glutamate transporter 1 and synaptophysin in photoreceptor cells, while it is colocalized with vesicular γ-aminobutyric acid ( The retina is a photoreceptive organ in which photosignals received by photoreceptor cells are transmitted to the optic nerve mainly through glutamatergic and γ-aminobutyric acid (GABA)ergic chemical transmission. There is, however, evidence that ATP and adenosine are involved as intercellular transmitters and play roles in various functions in the retina. 1-3)The retina has been reported to express various purinoceptors and enzymes involved in ATP hydrolysis.2,3) Photoreceptor cells express P2X2, P2X7, and P2Y1, 2, 4, and 6 receptors.2) P2X7 is localized presynaptically to rod and cone pedicles, and a functional study showed that 3′-O-(4-benzoyl)benzoyl-ATP (BzATP) increases the amplitude of the α-wave, suggesting a neuromodulatory role of purinergic neurotransmission.4) Intravitreal injection of ATP caused rapid loss of photoreceptors, which was reduced by coinjection of the P2X antagonist, pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), suggesting the involvement of purinergic chemical transmission in photoreceptor integrity. 5) Bipolar cells and horizontal cells also express P2X3-5 and 7 and P2Y1, 2, 6, and P2X7, respectively.2) Ganglion cells express both P2Xs and P2Y. 6) Stimulation of P2X7, with BzATP, an agonist of P2X7, induced death of the isolated ganglion cells through increases in intracellular Ca 2+ . 6) Loss of ganglion cells in vivo was also observed following injection of BzATP into the retina.7) It has also been reported that A1 and A3 receptors are involved in neuroprotection of ganglion cells. 8-11)Müller cells, retinal glial cells with numerous fine processes, which may make contact with neurons and non-neuronal cells, also express P2X7 and P2Y1, and their stimulation by specific agonists results in increased DNA synthesis and elicitation of the Ca 2+ response, respectively. 12)Extracellular ATP and its degradation product, adenosine, may trigger purinergic responses. In fact, Müller cells were reported to release ATP in a Ca 2+ -dependent manner.9) It was also reported that cultured chick retinal neurons took up radiolabeled ATP then relea...

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“…Different studies suggest nucleotides-induced increase in calcium levels and cellular contraction (Kawamura et al, 2003;Sugiyama et al, 2006). In this sense, dinucleotides polyphosphates may contribute to regulate capillary function in retina.…”

Section: Presence In Other Posterior Structuresmentioning

confidence: 99%

“…In this sense, dinucleotides polyphosphates may contribute to regulate capillary function in retina. Moreover, P2X7 receptor activation triggered pericyte apoptosis that may be improved by P2Y 4 inhibition (Sugiyama et al, 2006). For that action, ATP, diadenosine polyphosphates and other nucleotides balance have particular relevance in the environmental extracellular modulation and the concomitant activation of P2 receptors.…”

Section: Presence In Other Posterior Structuresmentioning

confidence: 99%

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

Carracedo

Crooke

Guzmán-Aránguez

et al. 2016

Progress in Retinal and Eye Research

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a b s t r a c tDinucleoside polyphosphates comprises a group of dinucleotides formed by two nucleosides linked by a variable number of phosphates, abbreviated NpnN (where n represents the number of phosphates). These compounds are naturally occurring substances present in tears, aqueous humour and in the retina. As the consequence of their presence, these dinucleotides contribute to many ocular physiological processes. On the ocular surface, dinucleoside polyphosphates can stimulate tear secretion, mucin release from goblet cells and they help epithelial wound healing by accelerating cell migration rate. These dinucleotides can also stimulate the presence of proteins known to protect the ocular surface against microorganisms, such as lysozyme and lactoferrin. One of the latest discoveries is the ability of some dinucleotides to facilitate the paracellular way on the cornea, therefore allowing the delivery of compounds, such as antiglaucomatous ones, more easily within the eye. The compound Ap 4 A has been described being abnormally elevated in patient's tears suffering of dry eye, Sjogren syndrome, congenital aniridia, or after refractive surgery, suggesting this molecule as biomarker for dry eye condition. At the intraocular level, some diadenosine polyphosphates are abnormally elevated in glaucoma patients, and this can be related to the stimulation of a P2Y 2 receptor that increases the chloride efflux and water movement in the ciliary epithelium. In the retina, the dinucleotide dCp 4 U, has been proven to be useful to help in the recovery of retinal detachments. Altogether, dinucleoside polyphosphates are a group of compounds which present relevant physiological actions but which also can perform promising therapeutic benefits.

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Effect of P2X7 Receptor Activation on the Retinal Blood Velocity of Diabetic Rabbits

Cited by 24 publications

References 28 publications

Nucleotides in the Eye: Focus on Functional Aspects and Therapeutic Perspectives

Nucleotides in the Eye: Focus on Functional Aspects and Therapeutic Perspectives

Expression of Vesicular Nucleotide Transporter in the Mouse Retina

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

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