The role of iron in retinal degeneration during bacterial infection

项目总结 当细菌侵入眼睛时，所造成的损害是迅速的和不可逆转的。这种类型的感染称为 眼内炎，是眼内手术最严重的并发症。患者的预后在很大程度上取决于 关于细菌的致病性、对抗生素的敏感性以及炎症的程度。这些 因素可能会影响进展到最坏的情况，在这种情况下，感染的眼睛必须完全 已删除。即使在较轻微的情况下，一些永久性的视力丧失也是常见的。因此，有必要 对于一种针对导致视力丧失的两个因素的治疗：细菌生长和神经毒性炎症。全 细菌的生存和繁殖需要铁。在感染期间，它们必须从宿主组织中获得铁。在……里面 作为回应，宿主细胞将进口铁以保护其免受细菌的侵袭，从而引发对铁获取的竞争。 然而，免疫细胞内的铁积累会促进炎症。在不同的动物模型中 对于感染和疾病，铁络合物既有抗菌作用，又有抗炎作用。我初步的体外实验 数据表明，铁螯合作用抑制了玻璃体(眼睛内的液体)中的细菌生长，而急性 铁的螯合作用对视网膜无毒。目标1将在这些结果的基础上展开，以确定 铁络合剂预防小鼠眼内炎。我将检查细菌生长的程度 随着时间的推移，视网膜结构被抑制，视网膜结构被保存。尽管减少细菌会自然地减少 发炎，铁螯合的直接抗炎作用还不清楚。因此，目标2将 研究铁蓄积和视网膜炎症之间的联系。利用小鼠眼内炎 模型，我将检测视网膜巨噬细胞/小胶质细胞内的铁水平，以及铁螯合剂的程度 减少视网膜炎症。这一结果将决定铁络合物的抗炎潜力。 治疗眼内炎。这项建议的总体目标是防止由细菌引起的视力丧失 感染。

PROJECT SUMMARY When bacteria invade the eye, the resulting damage is rapid and irreversible. This type of infection, called endophthalmitis, is the most severe complication of intraocular surgery. Patient outcome is heavily dependent on the pathogenicity of the bacteria, its susceptibility to antibiotics, and the extent of inflammation. These factors can influence progression to the worst-case scenario, where the infected eye must be completely removed. Even in milder cases, some amount of permanent vision loss is common. Therefore, there is need for a treatment which targets both contributors to vision loss: bacterial growth and neurotoxic inflammation. All bacteria require iron for survival and proliferation. During infection, they must obtain iron from host tissues. In response, host cells will import iron to shield it from bacteria, initiating a competition for iron acquisition. However, iron accumulation within immune cells can promote inflammation. In animal models of diverse infections and diseases, iron chelation is both anti-bacterial and anti-inflammatory. My preliminary ex vivo data suggests that iron chelation inhibits bacterial growth in vitreous (fluid from within the eye), and that acute iron chelation is nontoxic to the retina. Aim 1 will expand on these results to determine the effectiveness of an iron chelator at preventing endophthalmitis in mice. I will examine the extent to which bacterial growth is inhibited and retinal structure is preserved over time. Although reducing bacteria would naturally reduce inflammation, the direct anti-inflammatory contribution of iron chelation would be unclear. Therefore, Aim 2 will investigate the link between iron accumulation and retinal inflammation. Using the murine endophthalmitis model, I will examine iron levels within retinal macrophages/microglia, and to what extent an iron chelator reduces retinal inflammation. The result will determine the anti-inflammatory potential of iron chelation treatment for endophthalmitis. The overall goal of this proposal is to prevent vision loss caused by bacterial infection.