Neuroprotective effects of the cannabinoid agonist HU210 on retinal degeneration.
Cannabinoids have been demonstrated to exert neuroprotective effects on different types of neuronal insults. Here we have addressed the therapeutic potential of the synthetic cannabinoid HU210 on photoreceptor degeneration, synaptic connectivity and functional activity of the retina in the transgenic P23H rat, an animal model for autosomal dominant retinitis pigmentosa (RP). In P23H rats administered with HU210 (100 μg/kg, i.p.) from P24 to P90, ERG recordings showed an amelioration of vision loss, as compared to vehicle-administered animals. Under scotopic conditions, the maximum a-wave amplitudes recorded at P60 and P90 were higher in HU210-treated animals, as compared to the values obtained in untreated animals. The scotopic b-waves were significantly higher in treated animals than in untreated rats at P30, P60 and P90. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. HU210-treated animals had 40% more photoreceptors than untreated animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were also preserved in HU210-treated P23H rats. These results indicate that HU210 preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in P23H rats. These data suggest that cannabinoids are potentially useful to delay retinal degeneration in RP patients.
Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Pedro
P
Lax
Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Gema
G
Esquiva
Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain.
Cesare
C
Altavilla
Department of Physiology, Genetics and Microbiology, University of Alicante, Alicante, Spain; Institute Ramón Margalef, University of Alicante, Alicante, Spain. Electronic address: cuenca@ua.es.
Nicolás
N
Cuenca
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D063386:Cannabinoid Receptor Agonists / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004596:Electroretinography; D005136:Eye Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D055254:Night Vision; D010775:Photic Stimulation; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D055647:Rats, Transgenic; D012160:Retina / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D051245:Retinal Bipolar Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D015415:Biomarkers; D063386:Cannabinoid Receptor Agonists; D005136:Eye Proteins; D018696:Neuroprotective Agents; D013759:Dronabinol; C062018:HU 211
P23H; apoptosis; confocal microscopy; electroretinography; immunohistochemistry; neurodegeneration; retinitis pigmentosa