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Potential roles of (endo)cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection

By July 23, 2013No Comments

Volume 173, 2008, Pages 451–464
Glaucoma: An Open Window to Neurodegeneration and Neuroprotection

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Potential roles of (endo)cannabinoids in the treatment of glaucoma: from intraocular pressure control to neuroprotection

  • 1 Ophthalmological Unit, Department of Biopathology and Diagnostic Imaging, University of Rome “Tor Vergata,” Rome, Italy
  • 2 Experimental Neuropharmacology Center, “Mondino-Tor Vergata,” Fondazione C. Mondino-IRCCS, Rome, Italy
  • 3 Department of Experimental Medicine and Biochemical Sciences, University of Rome “Tor Vergata,” Rome, Italy
  • 4 Department of Pharmacobiological Sciences, University Magna Graecia, Catanzaro, Italy
  • 5 Department of Pharmacobiology, University of Calabria and UCHAD, Arcavacata di Rende (Cosenza) Italy
  • 6 Department of Biomedical Sciences, University of Teramo, Teramo, Italy
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Recent evidence shows that the endocannabinoid system is involved in the pathogenesis of numerous neurodegenerative diseases of the central nervous system. Pharmacologic modulation of cannabinoid receptors or the enzymes involved in the synthesis, transport, or breakdown of endogenous cannabinoids has proved to be a valid alternative to conventional treatment of these diseases. In this review, we will examine recent findings that demonstrate the involvement of the endocannabinoid system in glaucoma, a major neurodegenerative disease of the eye that is a frequent cause of blindness. Experimental findings indicate that the endocannabinoid system contributes to the control of intraocular pressure (IOP), by modulating both production and drainage of aqueous humor. There is also a growing body of evidence of the involvement of this system in mechanisms leading to the death of retinal ganglion cells, which is the end result of glaucoma. Molecules capable of interfering with the ocular endocannabinoid system could offer valid alternatives to the treatment of this disease, based not only on the reduction of IOP but also on neuroprotection.


  • cannabinoids;
  • intraocular pressure;
  • glaucoma;
  • neuroprotection;
  • retinal ganglion cells

Figures and tables from this article:

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Fig. 1. Activity of FAAH, NAPE-PLD, and AMT, and endogenous levels of AEA, in the retina of rats subjected to high IOP-induced ischemia for 45 min followed by 12 h reperfusion. Sham operated animals were exposed to the same surgical procedure without ischemia/reperfusion (100%=161±20 pmol/min per mg protein, for FAAH; 39±5 pmol/min per mg protein, for NAPE-PLD; 34±5 pmol/min per mg protein, for AMT; 20±4 pmol per mg protein, for AEA). The activity of FAAH and that of AMT was assayed also in the presence of specific blockers, i.e. 10 nM URB597 and 5 μM OMDM1, respectively. Data were expressed as mean±S.D. (n=3) and were analyzed by the Mann–Whitney U test. *Denotesp<0.01 versus sham (adapted with permission from Nucci et al., 2007b).
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Fig. 2. Effect of high IOP on Thy-1 expression in normal and treated retinas. Real Time-PCR value. Bars in the graph represent the relative percent expression of Thy1 mRNA in treated retinas, compared with control ischemic retinas (Ctrl). Each bar represents the average of data obtained from a pool of five animals, assayed in triplicate. Treatment with URB597 (URB+Is), an inhibitor of FAAH activity, or with MetAEA (Met+Is), a stable analog of anandamide, highly prevented the decrease in retinal Thy-1 levels typically induced by 45 min ischemia followed by 24 h reperfusion (Is). Interestingly, pretreatment with the CB1R antagonist, SR141716 (3 mg/kg i.p.; SR1+Met+Is) or with the selective TRPV1 antagonist, capsazepine (10 mg/kg, i.p.; Cap+Met+Is) minimized the neuroprotective effect of MetAEA. Below the label lane of the graph are reported the relative numerical values, expressed as mean, and ±S.E.M. values. Data were also analyzed by the Student’s t test. *denotes p<0.05 versus Is, **p<0.05 versus Met+Is (adapted with permission fromNucci et al., 2007b).
Table 1. Neuroprotective effect of drugs that modulate the endocannabinoid system
Note: High IOP-induced ischemia for 45 min was followed by 24 h reperfusion. For neuroprotection studies, animals were pretreated with the following compounds: the FAAH inhibitor URB597 (0.3 mg/kg), the AEA stable analog MetAEA (5 μl, 1 mM), the CB1R antagonist SR141716 (3 mg/kg), or the TRPV1 antagonist capsazepine (10 mg/kg). Cell counting was performed in the ganglion cell layer of ischemic/reperfused and sham-operated rat retinas stained with haematoxylin and eosin. The number of cells in the RGC layer was counted in six areas of retinal sections (n=5 per eye) under light microscopy. Data were expressed as mean±S.E.M. per area and were analyzed by the Student’s t test.*p<0.01 versus sham-operated; §p<0.01 versus ischemia/reperfusion; #p<0.01 versus MetAEA (adapted with permission from Nucci et al., 2007b).
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