Activation of P2X Receptors Induces Apoptosis in Human Retinal Pigment Epithelium

Yang, Dongli; Elner, Susan G.; Clark, Andrea; Hughes, Bret A.; Petty, Howard R.; Elner, Victor M.

doi:10.1167/iovs.10-6172

Cited by 51 publications

(69 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is known that ATP induces apoptosis in retinal cells [34]; therefore, Annexin V assays (see BMaterials and methodsŝ ection) were used on 661W cells in order to distinguish whether ATP treatment produced necrosis or apoptosis in this cellular model. In addition, we evaluated the efficiency of the incubation with Saf on mitigating cell apoptosis induced by ATP.…”

Section: Saffron Decreases Retinal Photoreceptor Apoptosis Induced Bymentioning

confidence: 99%

Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors

Corso

Cavallero

Baroni

et al. 2016

Purinergic Signalling

View full text Add to dashboard Cite

P2X7-type purinergic receptors are distributed throughout the nervous system where they contribute to physiological and pathological functions. In the retina, this receptor is found in both inner and outer cells including microglia modulating signaling and health of retinal cells. It is involved in retinal neurodegenerative disorders such as retinitis pigmentosa and age-related macular degeneration (AMD). Experimental studies demonstrated that saffron protects photoreceptors from light-induced damage preserving both retinal morphology and visual function and improves retinal flicker sensitivity in AMD patients. To evaluate a possible interaction between saffron and P2X7 receptors (P2X7Rs), different cellular models and experimental approaches were used. We found that saffron positively influences the viability of mouse primary retinal cells and photoreceptor-derived 661W cells exposed to ATP, and reduced the ATP-induced intracellular calcium increase in 661W cells. Similar results were obtained on HEK cells transfected with recombinant rat P2X7R but not on cells transfected with rat P2X2R. Finally, patch-clamp experiments showed that saffron inhibited cationic currents in HEK-P2X7R cells. These results point out a novel mechanism through which saffron may exert its protective role in neurodegeneration and support the idea that P2X7-mediated calcium signaling may be a crucial therapeutic target in the treatment of neurodegenerative diseases.

show abstract

Section: Saffron Decreases Retinal Photoreceptor Apoptosis Induced Bymentioning

confidence: 99%

Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors

Corso

Cavallero

Baroni

et al. 2016

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…However, little is known about the apoptotic role of ATP in RPE cells. P2X7 receptor expression has been shown in cultured human ARPE-19 cells (Dutot et al, 2008) and human RPE cells isolated from donor eyes (Yang et al, 2011). P2X7 activation is caused by exposing human ARPE-19 cells to ATP and BzATP, triggering pore formation and YO-PRO-1 (4-[(3-methyl-1,3-benzoxazol-2(3H)-ylidene)methyl]-1-[3-(trimethylammonio)propyl]quinolinium diiodide) dye uptake in these cells (Dutot et al, 2008).…”

Section: Rpe Nucleotidesmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…For instance, in a given patient, it is possible to study PBMC to access the expression of the P2X7 protein, the product of the same P2RX7 that is expressed in retinal epithelial cells. Concerning the relevance of this approach, it is worth mentioning that primary cultures of human retinal epithelial cells that express P2X7 protein [55] are responsive to IFNstimulation leading to T. gondii elimination in a pathway independent of nitric oxide (NO) [36].…”

Section: Resultsmentioning

confidence: 99%

Immunological and Immunogenetic Parameters on the Diversity of Ocular Toxoplasmosis: Evidence to Support Morphological Criteria to Classify Retinal/Retinochoroidal Scar Lesions in Epidemiologic Surveys

Bahia-Oliveira¹,

Rangel²,

Boechat³

et al. 2012

Toxoplasmosis - Recent Advances

View full text Add to dashboard Cite

Activation of P2X Receptors Induces Apoptosis in Human Retinal Pigment Epithelium

Abstract: These findings suggest that P2X receptors, especially P2X(7) receptors, contribute to ATP- and BzATP-induced Ca(2+) signaling and apoptosis in the RPE. Abnormal Ca(2+) homeostasis through the activation of P2X receptors could cause the dysfunction and apoptosis of RPE that underlie AMD.

Cited by 51 publications

References 56 publications

Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors

Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors

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

Immunological and Immunogenetic Parameters on the Diversity of Ocular Toxoplasmosis: Evidence to Support Morphological Criteria to Classify Retinal/Retinochoroidal Scar Lesions in Epidemiologic Surveys

Contact Info

Product

Resources

About