Neuroprotective effects of the cannabinoid agonist HU210 on retinal degeneration

Exp Eye Res. 2014 Mar;120:175-85. doi: 10.1016/j.exer.2014.01.019. Epub 2014 Feb 1.

Abstract

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.

Keywords: P23H; apoptosis; confocal microscopy; electroretinography; immunohistochemistry; neurodegeneration; retinitis pigmentosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cannabinoid Receptor Agonists / therapeutic use*
  • Cell Survival / drug effects
  • Disease Models, Animal*
  • Dronabinol / analogs & derivatives*
  • Dronabinol / therapeutic use
  • Electroretinography
  • Eye Proteins / metabolism
  • Microscopy, Confocal
  • Neuroprotective Agents / therapeutic use*
  • Night Vision
  • Photic Stimulation
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / pathology
  • Rats
  • Rats, Transgenic
  • Retina / drug effects*
  • Retina / metabolism
  • Retina / physiopathology
  • Retinal Bipolar Cells / drug effects
  • Retinal Bipolar Cells / metabolism
  • Retinal Bipolar Cells / pathology
  • Retinitis Pigmentosa / drug therapy*
  • Retinitis Pigmentosa / metabolism
  • Retinitis Pigmentosa / physiopathology

Substances

  • Biomarkers
  • Cannabinoid Receptor Agonists
  • Eye Proteins
  • Neuroprotective Agents
  • Dronabinol
  • HU 211