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Protective effects of the sigma agonist Pre-084 in the rat retina
  1. Giuseppina Cantarella1,
  2. Claudio Bucolo1,2,
  3. Giulia Di Benedetto1,
  4. Salvatore Pezzino1,
  5. Laurence Lempereur1,
  6. Rosa Calvagna1,
  7. Silvia Clementi1,
  8. Piero Pavone1,
  9. Lucia Fiore1,
  10. Renato Bernardini1
  1. 1
    Department of Experimental and Clinical Pharmacology, University of Catania School of Medicine, 95125 Catania, Italy
  2. 2
    Ocular Pharmacology Centre, University of Catania School of Medicine, 95125 Catania, Italy
  1. Renato Bernardini, Department of Experimental and Clinical Pharmacology, University of Catania School of Medicine, Viale Andrea Doria 6, 95125 Catania, Italy; bernardi{at}unict.it

Abstract

Aim: With the rationale that amyloid beta (AB) is toxic to 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 anaesthetised 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. Lactic dehydrogenase (LDH) levels were measured as a cytotoxicity marker.

Results: All TRAIL receptors were expressed in rat retinas. Intravitreal injection of AB in rat eyes induced overexpression of TRAIL and the proapoptotic protein Bax, as well as phosphorylation of JNK. All these effects of AB were abrogated by pretreatment 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 hypothesise that σ1 receptor agonists could represent potential pharmacological tools for restraining AB related retinal damage.

  • cytokines
  • receptors
  • retinal protection

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Footnotes

  • Abbreviations:
    AB

    amyloid beta

    ECL

    enhanced chemiluminescence

    JNK

    Jun-N terminal kinase

    LDH

    lactic dehydrogenase

    TRAIL

    tumour necrosis factor related apoptosis inducing ligand

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