Cantarella Giuseppina, Bucolo Claudio, Di Benedetto Giulia, Pezzino Salvatore, Lempereur Laurence, Calvagna Rosa, Clementi Silvia, Pavone Piero, Fiore Lucia, Bernardini Renato
Department of Experimental and Clinical Pharmacology, University of Catania School of Medicine, Viale Andrea Doria 6, 95125 Catania, Italy.
Br J Ophthalmol. 2007 Oct;91(10):1382-4. doi: 10.1136/bjo.2007.118570. Epub 2007 May 23.
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 sigma 1 receptor agonists in these processes.
AB and the sigma 1 receptor agonist Pre-084 were injected intravitreally in the anaesthetised rat. In additional experiments, the sigma 1 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.
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 sigma(1) receptor agonist Pre-084.
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 sigma(1) receptor agonists could represent potential pharmacological tools for restraining AB related retinal damage.
基于β淀粉样蛋白（Aβ）对视网膜有毒性这一理论基础，我们在此评估了肿瘤坏死因子相关凋亡诱导配体（TRAIL），一种Aβ毒性及相关信号转导的介质，在大鼠模型中的作用。我们还试图证明σ1受体激动剂在这些过程中可能的保护作用。
将Aβ和σ1受体激动剂Pre-084玻璃体内注射到麻醉的大鼠体内。在额外的实验中，给予σ1受体拮抗剂BD1047以评估Pre-084作用的特异性。对视网膜进行蛋白质免疫印迹分析，以评估不同处理后视网膜中TRAIL及其受体的表达，以及Bax和磷酸化JNK的表达。测量乳酸脱氢酶（LDH）水平作为细胞毒性标志物。
所有TRAIL受体均在大鼠视网膜中表达。向大鼠眼玻璃体内注射Aβ可诱导TRAIL和促凋亡蛋白Bax的过表达，以及JNK的磷酸化。Aβ的所有这些作用均被σ1受体激动剂Pre-084预处理所消除。
TRAIL很可能是Aβ对视网膜产生作用的介质。鉴于它们对TRAIL表达具有特异性抑制作用，推测σ1受体激动剂可能是抑制Aβ相关视网膜损伤的潜在药理学工具，这似乎是合理的。
