Involvement of the Endocannabinoid System in Retinal Damage after High Intraocular Pressure–Induced Ischemia in Rats

Nucci, Carlo Alberto; Gasperi, Valeria; Tartaglione, R.; Cerulli, Angelica; Terrinoni, Alessandro; Bari, Monica; Simone, Carla; Agró, Alessandro Finazzi; Morrone, Luigi Antonio; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Maccarrone, Mauro

doi:10.1167/iovs.06-1355

Cited by 112 publications

(111 citation statements)

References 61 publications

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“…The physiological importance of the endocannabinoid system in IOP regulation is further emphasized with the finding that 2-AG levels are significantly reduced in human glaucomatous ciliary muscle (Chen et al, 2005). In addition to these findings, endocannabinoids have been postulated to play a neuro-protective role in a high IOP-induced retina ischaemia model of glaucoma (Nucci et al, 2007). Anandamide/arachidonylethanolamide levels have been found to be increased in cornea, ciliary body, choroid and retina in patients with diabetic retinopathy and age-related macular degeneration (Matias et al, 2006), suggesting other ocular pathologies may also involve alterations in endocannabinoid signalling.…”

Section: Discussionmentioning

confidence: 98%

Agonist‐dependent cannabinoid receptor signalling in human trabecular meshwork cells

McIntosh

Hudson

Yegorova

et al. 2007

British J Pharmacology

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Background and purpose: Trabecular meshwork (TM) is an ocular tissue involved in the regulation of aqueous humour outflow and intraocular pressure (IOP). CB 1 receptors (CB 1 ) are present in TM and cannabinoid administration decreases IOP. CB 1 signalling was investigated in a cell line derived from human TM (hTM). Experimental approach: CB 1 signalling was investigated using ratiometric Ca 2 þ imaging, western blotting and infrared In-Cell Western analysis. Key results: WIN55212-2, a synthetic aminoalkylindole cannabinoid receptor agonist (10-100 mM) increased intracellular Ca 2 þ in hTM cells. WIN55,212-2-mediated Ca 2 þ increases were blocked by AM251, a CB 1 antagonist, but were unaffected by the CB 2 antagonist, AM630. The WIN55,212-2-mediated increase in [Ca 2 þ ] i was pertussis toxin (PTX)-insensitive, therefore, independent of G i/o coupling, but was attenuated by a dominant negative Ga q/11 subunit, implicating a G q/11 signalling pathway. The increase in [Ca 2 þ ] i was dependent upon PLC activation and mobilization of intracellular Ca 2 þ stores. A PTXsensitive increase in extracellular signal-regulated kinase (ERK1/2) phosphorylation was also observed in response to WIN55,212-2, indicative of a G i/o signalling pathway. CB 1 -G q/11 coupling to activate PLC-dependent increases in Ca 2 þ appeared to be specific to WIN55,212-2 and were not observed with other CB 1 agonists, including CP55,940 and methanandamide. CP55940 produced PTX-sensitive increases in [Ca 2 þ ] i at concentrations Z15 mM, and PTX-sensitive increases in ERK1/2 phosphorylation. Conclusions and implications: This study demonstrates that endogenous CB 1 couples to both G q/11 and G i/o in hTM cells in an agonist-dependent manner. Cannabinoid activation of multiple CB 1 signalling pathways in TM tissue could lead to differential changes in aqueous humour outflow and IOP.

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Section: Discussionmentioning

confidence: 98%

Agonist‐dependent cannabinoid receptor signalling in human trabecular meshwork cells

McIntosh

Hudson

Yegorova

et al. 2007

British J Pharmacology

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“…Although, several studies have shown that topical administration of cannabinoids reduces IOP (Pate et al, 1995;Laine et al, 2001;Chien et al, 2003) by modulating both production and drainage of aqueous humor (Chien et al, 2003;Njie et al, 2006) a number of studies reported that cannabinoids exert neuroprotective effects in the eye against glutamate-induced excitotoxicity (Jarvinen et al, 2002;Crandall et al, 2007;Nucci et al, 2007bNucci et al, , 2008Duncan et al, 2011), with potential implications for the treatment of glaucoma. (Tomida et al, 2004;Yazulla, 2008).…”

Section: Cannabinoidsmentioning

confidence: 99%

“…Interestingly, some studies suggested that inhibition of glutamate release represents a key mechanism involved in neuroprotection mediated by the cannabinoid system (Braida et al, 2000;Sinor et al, 2000;Marsicano et al, 2003;Gobira et al, 2015;Lin et al, 2015). In 2007, our group using an animal model of acute glaucoma reported that inhibition of fatty acid amide hydrolase (FAAH) or administration of metanandamide, a stable analogue of anandamide, minimize RGC loss caused by ischemia/reperfusion and that MK801, a noncompetitive NMDA receptors antagonist, controls anandamide degradation through FAAH (Nucci et al, 2007b). Accordingly, it is likely that excitotoxic stimuli may affect the metabolism of endocannabinoids in the mammalian retina.…”

Section: Cannabinoidsmentioning

confidence: 99%

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

Nucci

Russo

Martucci

et al. 2016

European Journal of Pharmacology

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a b s t r a c tGlaucoma is a disease where retinal ganglion cells (RGC) are specifically affected though a number of evidences endorse the hypothesis that glaucoma is a neuro-degenerative disorder of the central nervous system and suggest a possible connection between glaucomatous damage and cerebrovascular alterations. The mechanisms underlying RGC loss are not yet fully known but alterations of the autophagy machinery have been recently proposed as a potential contributing factor as for Alzheimer's disease.Here we review the current literature on new strategies for neuroprotection in glaucoma, focusing on pharmacologic strategies to minimize RGC damage.

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“…Although the retina has no sensory innervations, substance P (SP)-and calcitonin gene-related peptide (CGRP)-containing amacrine and ganglion cells have been observed in the retina in various species including humans (49-51). Furthermore, several experimental studies have suggested that these neuropeptides are involved in various retinal diseases (52)(53)(54). Previously, an increase in SP and CGRP immunoreactivity was observed in the retina after electric stimulation of the trigeminal ganglion (55).…”

Section: Introductionmentioning

confidence: 99%

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis

Bianchi

Scarinci

Ripandelli

et al. 2012

International Journal of Molecular Medicine

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Abstract. Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

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Involvement of the Endocannabinoid System in Retinal Damage after High Intraocular Pressure–Induced Ischemia in Rats

Abstract: 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.

Cited by 112 publications

References 61 publications

Agonist‐dependent cannabinoid receptor signalling in human trabecular meshwork cells

Agonist‐dependent cannabinoid receptor signalling in human trabecular meshwork cells

New strategies for neuroprotection in glaucoma, a disease that affects the central nervous system

Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis

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