Adenosine receptor expression in the adult zebrafish retina

Grillo, Stephanie L.; McDevitt, Dillon S.; Voas, Matthew G.; Khan, Amanda S.; Grillo, Michael A.; Stella, Salvatore

doi:10.1007/s11302-019-09667-0

Cited by 9 publications

(5 citation statements)

References 79 publications

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“…A recent study involving zebrafish studied the expression of all four adenosine receptor subtypes, reporting A2A and A2B receptors in both the inner and outer plexiform and nuclear layers, and the ganglion cell layer. [20] Our results demonstrated similar distribution of the A2B receptors throughout the retina, but we primarily observed the A2A receptors expressed within the vasculature. Much like our results, A3 receptors were primarily in the inner and ONLs and A1 receptors were primarily in the inner and OPLs.…”

Section: Discussionsupporting

confidence: 71%

“…Much like our results, A3 receptors were primarily in the inner and ONLs and A1 receptors were primarily in the inner and OPLs. [20] Therefore, our results indicate some overlap with the preclinical models mapping the expression of adenosine receptors in the retina, but we did find differences in human retinal expression compared to animal models.…”

Section: Discussionmentioning

confidence: 57%

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Adenosine Receptors Expression in Human Retina and Choroid with Age-related Macular Degeneration

Song

Zaitoun

Wang

et al. 2023

JOVR

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Purpose: Adenosine signaling modulates ocular inflammatory processes, and its antagonism mitigates neovascularization in both newborns and preclinical models of ocular neovascularization including age-related macular degeneration (AMD). The adenosine receptor expression patterns have not been well characterized in the human retina and choroid. Methods: Here we examined the expression of adenosine receptor subtypes within the retina and choroid of human donor eyes with and without AMD. Antibodies specifically targeting adenosine receptor subtypes A1, A2A, A2B, and A3 were used to assess their expression patterns. Quantitative real-time PCR analysis was used to confirm gene expression of these receptors within the normal human retina and choroid. Results: We found that all four receptor subtypes were expressed in several layers of the retina, and within the retinal pigment epithelium and choroid. The expression of A1 receptors was more prominent in the inner and outer plexiform layers, where microglia normally reside, and supported by RNA expression in the retina. A2A and A2B showed similar expression patterns with prominent expression in the vasculature and retinal pigment epithelium. No dramatic differences in expression of these receptors were observed in eyes from patients with dry or wet AMD compared to control, with the exception A3 receptors. Eyes with dry AMD lost expression of A3 in the photoreceptor outer segments compared with eyes from control or wet AMD. Conclusion: The ocular presence of adenosine receptors is consistent with their proposed role in modulation of inflammation in both the retina and choroid, and their potential targeting for AMD treatment.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 57%

Adenosine Receptors Expression in Human Retina and Choroid with Age-related Macular Degeneration

Song

Zaitoun

Wang

et al. 2023

JOVR

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“…Such multifaceted effects of resveratrol in the different retinal layers may be associated with the cellular distribution of the adenosine receptor subtypes. Adenosine A2 receptors are expressed predominantly in the GCL and INL ( 43 ), whilst adenosine A3 receptors are primarily found in the ONL ( 44 ). Activated A2 receptors can mediate the protective effects on ischemic neurons, whereas A3 receptors have been previously documented to serve a noxious role in triggering neuron apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol protects retinal ganglion cells against ischemia induced damage by increasing Opa1 expression

Pang

Qin

et al. 2020

Int J Mol Med

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Loss of idiopathic retinal ganglion cells (RGcs) leads to irreversible vision defects and is considered the primary characteristic of glaucoma. However, effective treatment strategies in terms of RGc neuroprotection remain elusive. In the present study, the protective effects of resveratrol on RGc apoptosis, and the mechanisms underlying its effects were investigated, with a particular emphasis on the function of optic atrophy 1 (Opa1). In an ischemia/reperfusion (I/R) injury model, the notable thinning of the retina, significant apoptosis of RGcs, reduction in Opa1 expression and long Opa1 isoform to short Opa1 isoform ratios (L-Opa1/S-Opa1 ratio) were observed, all of which were reversed by resveratrol administration. Serum deprivation resulted in reductions in R28 cell viability, superoxide dismutase (SOd) activity, Opa1 expression and induced apoptosis, which were also partially reversed by resveratrol treatment. To conclude, results from the present study suggest that resveratrol treatment significantly reduced retinal damage and RGc apoptosis in I/R injury and serum deprivation models. In addition, resveratrol reversed the downregulated expression of Opa1 and reduced SOd activity. Mechanistically, resveratrol influenced mitochondrial dynamics by regulating the L-Opa1/S-Opa1 ratio. Therefore, these observations suggest that resveratrol may exhibit potential as a therapeutic agent for RGc damage in the future.

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“…Several studies show a preeminent role of A2a receptors in the outer retina (McIntosh and Blazynski, 1994;Li et al, 2013;Huang et al, 2014;Cao et al, 2021). However, A2ARimmunoreactivity was shown to be expressed as puncta in the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer retina of the zebrafish (Grillo et al, 2019).…”

Section: A2a Adenosine Receptormentioning

confidence: 99%

Chemical signaling in the developing avian retina: Focus on cyclic AMP and AKT-dependent pathways

Duarte-Silva

Ximenes

Guimarães-Souza

et al. 2022

Front. Cell Dev. Biol.

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Communication between developing progenitor cells as well as differentiated neurons and glial cells in the nervous system is made through direct cell contacts and chemical signaling mediated by different molecules. Several of these substances are synthesized and released by developing cells and play roles since early stages of Central Nervous System development. The chicken retina is a very suitable model for neurochemical studies, including the study of regulation of signaling pathways during development. Among advantages of the model are its very well-known histogenesis, the presence of most neurotransmitter systems found in the brain and the possibility to make cultures of neurons and/or glial cells where many neurochemical functions develop in a similar way than in the intact embryonic tissue. In the chicken retina, some neurotransmitters or neuromodulators as dopamine, adenosine, and others are coupled to cyclic AMP production or adenylyl cyclase inhibition since early stages of development. Other substances as vitamin C and nitric oxide are linked to the major neurotransmitter glutamate and AKT metabolism. All these different systems regulate signaling pathways, including PKA, PKG, SRC, AKT and ERK, and the activation of the transcription factor CREB. Dopamine and adenosine stimulate cAMP accumulation in the chick embryo retina through activation of D1 and A2a receptors, respectively, but the onset of dopamine stimulation is much earlier than that of adenosine. However, adenosine can inhibit adenylyl cyclase and modulate dopamine-dependent cAMP increase since early developmental stages through A1 receptors. Dopamine stimulates different PKA as well as EPAC downstream pathways both in intact tissue and in culture as the CSK-SRC pathway modulating glutamate NMDA receptors as well as vitamin C release and CREB phosphorylation. By the other hand, glutamate modulates nitric oxide production and AKT activation in cultured retinal cells and this pathway controls neuronal survival in retina. Glutamate and adenosine stimulate the release of vitamin C and this vitamin regulates the transport of glutamate, activation of NMDA receptors and AKT phosphorylation in cultured retinal cells. In the present review we will focus on these reciprocal interactions between neurotransmitters or neuromodulators and different signaling pathways during retinal development.

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Adenosine receptor expression in the adult zebrafish retina

Cited by 9 publications

References 79 publications

Adenosine Receptors Expression in Human Retina and Choroid with Age-related Macular Degeneration

Adenosine Receptors Expression in Human Retina and Choroid with Age-related Macular Degeneration

Resveratrol protects retinal ganglion cells against ischemia induced damage by increasing Opa1 expression

Chemical signaling in the developing avian retina: Focus on cyclic AMP and AKT-dependent pathways

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