Involvement of the endocannabinoid system in retinal damage after high intraocular pressure-induced ischemia in rats

Carlo Nucci, Valeria Gasperi, Rosanna Tartaglione, Angelica Cerulli, Alessandro Terrinoni, Monica Bari, Chiara De Simone, Alessandro Finazzi Agrò, Luigi Antonio Morrone, Maria Tiziana Corasaniti, Giacinto Bagetta, Mauro Maccarrone

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Abstract

PURPOSE. To evaluate whether high intraocular pressure (IOP)-induced ischemia is associated with modifications in the retinal endocannabinoid metabolism and to ascertain whether drugs that interfere with the endocannabinoid system may prevent retinal damage due to ischemic insult. METHODS. Anandamide (AEA) synthesis, transport, hydrolysis, and AEA endogenous levels were assessed by means of high-performance liquid chromatography in the retinas of rats undergoing 45 minutes of ischemia followed by 12 hours of reperfusion. Under these experimental conditions, binding to cannabinoid (CB1R) and vanilloid (TRPV1) receptor was assessed with rapid-filtration assays. AEA-hydrolase (FAAH, fatty acid amide hydrolase), CB1R and TRPV1 protein content was determined by enzyme-linked immunosorbent assay. Finally, to characterize the neuroprotective profile of drugs that interfere with the endocannabinoid system, cell counting in the retinal ganglion cell (RGC) layer and real-time polymerase chain reactions for Thy-1 mRNA expression were used. RESULTS. In rat retina, ischemic insult followed by reperfusion resulted in enhanced FAAH activity and protein expression paralleled by a significant decrease in the endogenous AEA tone, whereas the AEA-membrane transporter or the AEA-synthase NAPE-PLD (N-acyl-phosphatidylethanolamine-hydrolyzing-phospholipase-D) were not affected. Retinal ischemia-reperfusion decreased the expression of cannabinoid (CB1) and vanilloid (TRPV1) receptors. Systemic administration of a specific FAAH inhibitor (e.g., URB597) reduced enzyme activity and minimized the retinal damage observed in ischemic-reperfused samples. Similarly, intravitreal injection of the AEA stable analogue, R(+)-methanandamide, reduced cell loss in the RGC layer, and this was prevented by systemic administration of a CB1 or TRPV1 selective antagonist (e.g., SR141716 and capsazepine, respectively). CONCLUSIONS. The original observation that retinal ischemia-reperfusion reduces endogenous AEA via enhanced expression of FAAH supports the deduction that this is implicated in retinal cell loss caused by high IOP in the RGC layer.

Original languageEnglish
Pages (from-to)2997-3004
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume48
Issue number7
DOIs
Publication statusPublished - Jul 2007

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Endocannabinoids
Intraocular Pressure
Reperfusion
Retinal Ganglion Cells
Ischemia
TRPV Cation Channels
rimonabant
Cannabinoids
Retina
Phospholipase D
Intravitreal Injections
Membrane Transport Proteins
Neuroprotective Agents
Hydrolases
Real-Time Polymerase Chain Reaction
Proteins
Hydrolysis
Enzyme-Linked Immunosorbent Assay
High Pressure Liquid Chromatography
Messenger RNA

ASJC Scopus subject areas

  • Ophthalmology

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Involvement of the endocannabinoid system in retinal damage after high intraocular pressure-induced ischemia in rats. / Nucci, Carlo; Gasperi, Valeria; Tartaglione, Rosanna; Cerulli, Angelica; Terrinoni, Alessandro; Bari, Monica; De Simone, Chiara; Agrò, Alessandro Finazzi; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Maccarrone, Mauro.

In: Investigative Ophthalmology and Visual Science, Vol. 48, No. 7, 07.2007, p. 2997-3004.

Research output: Contribution to journalArticle

Nucci, C, Gasperi, V, Tartaglione, R, Cerulli, A, Terrinoni, A, Bari, M, De Simone, C, Agrò, AF, Morrone, LA, Corasaniti, MT, Bagetta, G & Maccarrone, M 2007, 'Involvement of the endocannabinoid system in retinal damage after high intraocular pressure-induced ischemia in rats', Investigative Ophthalmology and Visual Science, vol. 48, no. 7, pp. 2997-3004. https://doi.org/10.1167/iovs.06-1355
Nucci, Carlo ; Gasperi, Valeria ; Tartaglione, Rosanna ; Cerulli, Angelica ; Terrinoni, Alessandro ; Bari, Monica ; De Simone, Chiara ; Agrò, Alessandro Finazzi ; Morrone, Luigi Antonio ; Corasaniti, Maria Tiziana ; Bagetta, Giacinto ; Maccarrone, Mauro. / Involvement of the endocannabinoid system in retinal damage after high intraocular pressure-induced ischemia in rats. In: Investigative Ophthalmology and Visual Science. 2007 ; Vol. 48, No. 7. pp. 2997-3004.
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AU - Terrinoni, Alessandro

AU - Bari, Monica

AU - De Simone, Chiara

AU - Agrò, Alessandro Finazzi

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N2 - PURPOSE. To evaluate whether high intraocular pressure (IOP)-induced ischemia is associated with modifications in the retinal endocannabinoid metabolism and to ascertain whether drugs that interfere with the endocannabinoid system may prevent retinal damage due to ischemic insult. METHODS. Anandamide (AEA) synthesis, transport, hydrolysis, and AEA endogenous levels were assessed by means of high-performance liquid chromatography in the retinas of rats undergoing 45 minutes of ischemia followed by 12 hours of reperfusion. Under these experimental conditions, binding to cannabinoid (CB1R) and vanilloid (TRPV1) receptor was assessed with rapid-filtration assays. AEA-hydrolase (FAAH, fatty acid amide hydrolase), CB1R and TRPV1 protein content was determined by enzyme-linked immunosorbent assay. Finally, to characterize the neuroprotective profile of drugs that interfere with the endocannabinoid system, cell counting in the retinal ganglion cell (RGC) layer and real-time polymerase chain reactions for Thy-1 mRNA expression were used. RESULTS. In rat retina, ischemic insult followed by reperfusion resulted in enhanced FAAH activity and protein expression paralleled by a significant decrease in the endogenous AEA tone, whereas the AEA-membrane transporter or the AEA-synthase NAPE-PLD (N-acyl-phosphatidylethanolamine-hydrolyzing-phospholipase-D) were not affected. Retinal ischemia-reperfusion decreased the expression of cannabinoid (CB1) and vanilloid (TRPV1) receptors. Systemic administration of a specific FAAH inhibitor (e.g., URB597) reduced enzyme activity and minimized the retinal damage observed in ischemic-reperfused samples. Similarly, intravitreal injection of the AEA stable analogue, R(+)-methanandamide, reduced cell loss in the RGC layer, and this was prevented by systemic administration of a CB1 or TRPV1 selective antagonist (e.g., SR141716 and capsazepine, respectively). CONCLUSIONS. The original observation that retinal ischemia-reperfusion reduces endogenous AEA via enhanced expression of FAAH supports the deduction that this is implicated in retinal cell loss caused by high IOP in the RGC layer.

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