Syed Husnain, Safa Rukhsana, Chidlow Glyn, Osborne Neville N
Nuffield Laboratory of Ophthalmology, Oxford University, Walton Street, Oxford OX2 6AW, UK.
Neurochem Int. 2006 Jun;48(8):708-17. doi: 10.1016/j.neuint.2005.12.007. Epub 2006 Feb 7.
Endothelins exert pathological effects in the eye and much interest centres on their role in causing retinal neuronal death in ischemic diseases like glaucoma. In the present study the influence of the non-selective endothelin antagonist, sulfisoxazole on raised intraocular pressure-induced ischemia to the rat retina was investigated. Moreover, in vitro studies on primary rat retinal cultures were undertaken to see whether sulfisoxazole is able to blunt the toxic effect of lipopolysaccharide (LPS) to retinal neurones. In order to determine whether sulfisoxazole provides protection to the retina the a- and b-wave amplitudes of the electroretinogram (ERG), the localisation of retinal choline acetyltransferase (ChAT), nitric oxide synthase (nNOS) and Thy-1 and the retinal mRNA levels of Thy-1 and FGF-2 were deduced in retinas subjected to ischemia in the absence or presence of sulfisoxazole. The results showed that the ischemia-induced changes to the a- and b-wave amplitudes of the ERG and changes associated with the localisation of ChAT, nNOS and Thy-1 to be significantly blunted by sulfisoxazole. However, while the ischemia-induced changes to Thy-1 and FGF-2 mRNAs were reduced by sulfisoxazole, the reduction was non-significant. The in vitro studies provided support for the protective effect of sulfisoxazole. Here, it was clearly shown that sulfisoxazole attenuated the elevation of nitric oxide (deduced by measuring nitrite) and the reduction in numbers of GABA-containing neurones caused by LPS. The present study provides evidence for the first time that endothelin antagonist can protect the retina from ischemic-like insults as occurs in glaucoma.
内皮素在眼部发挥病理作用，许多研究聚焦于其在青光眼等缺血性疾病中导致视网膜神经元死亡的作用。在本研究中，研究了非选择性内皮素拮抗剂磺胺异恶唑对大鼠视网膜高眼压诱导缺血的影响。此外，对原代大鼠视网膜培养物进行了体外研究，以观察磺胺异恶唑是否能够减弱脂多糖（LPS）对视网膜神经元的毒性作用。为了确定磺胺异恶唑是否能保护视网膜，在存在或不存在磺胺异恶唑的情况下，对缺血视网膜的视网膜电图（ERG）的a波和b波振幅、视网膜胆碱乙酰转移酶（ChAT）、一氧化氮合酶（nNOS）和Thy-1的定位以及Thy-1和FGF-2的视网膜mRNA水平进行了推断。结果表明，磺胺异恶唑可显著减弱缺血诱导的ERG的a波和b波振幅变化以及与ChAT、nNOS和Thy-1定位相关的变化。然而，虽然磺胺异恶唑可减少缺血诱导的Thy-1和FGF-2 mRNA变化，但这种减少并不显著。体外研究为磺胺异恶唑的保护作用提供了支持。在此，清楚地表明磺胺异恶唑可减弱LPS引起的一氧化氮升高（通过测量亚硝酸盐推断）和含GABA神经元数量的减少。本研究首次提供证据表明内皮素拮抗剂可保护视网膜免受青光眼等缺血样损伤。
