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Protective effects of the sigma agonist pre-084 in the rat retina
  1. Giuseppina Cantarella (gcantare{at}unict.it),
  2. Claudio Bucolo (bucocla{at}unict.it),
  3. Giulia Di Benedetto (giuliadibenedetto{at}libero.it),
  4. Salvatore Pezzino (salvatore.pezzino12{at}virgilio.it),
  5. Laurence Lempereur (lempereu{at}unict.it),
  6. Rosa Calvagna,
  7. Silvia Clementi,
  8. Piero Pavone (lpavone{at}unict.it),
  9. Lucia Fiore (fiore{at}unict.it),
  10. Renato Bernardini (bernardi{at}unict.it)
  1. University of Catania School of Medicine, Italy
  2. University of Catania School of Medicine, Italy
  3. University of Catania School of Medicine, Italy
  4. University of Catania School of Medicine, Italy
  5. University of Catania School of Medicine, Italy
  6. University of Catania School of Medicine, Italy
  7. University of Catania School of Medicine, Italy
  8. University of Catania School of Medicine, Italy
  9. University of Catania School of Medicine, Italy
  10. University of Catania School of Medicine, Italy

    Abstract

    Aim: With the rationale that amyloid-beta (AB) is toxic for the retina, we here assessed the role of TRAIL, a mediator of AB toxicity, and related signal transduction, in a rat model. We also attempted to demonstrate possible protective effects of σ1 receptor agonists in these processes.

    Methods: AB and the σ1 receptor agonist PRE-084 were injected intravitreally in the anesthesized rat. In additional experiments, the σ1 receptor antagonist BD1047 was administered to assess specificity of the effects of PRE-084. Western blot analysis was performed on retinas to evaluate the expression of TRAIL and TRAIL receptors in the retina, as well as of Bax and phosphorylated JNK following the different treatments. LDH levels were measured as a citotoxicity marker.

    Results: All TRAIL receptors were expressed in rat retinas. Intravitreal injection of AB in rat eyes induced over-expression of TRAIL and the proapoptotic protein Bax, as well as phosphorylation of JNK. All these effects of AB were abrogated by pre-treatment with the σ1 receptor agonist PRE-084.

    Conclusions: It is likely that TRAIL is a mediator of AB effects on the retina. In light of their specific inhibitory effects upon TRAIL expression, it is plausible to hypothesize that σ1 receptor agonists could represent potential pharmacological tools for restraining AB-related retinal damage.

    • cytokines
    • receptors
    • retinal protection

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