Department of Ophthalmology, Visual & Anatomical Sciences, Kresge Eye Institute, Wayne State University School of Medicine, 4717 St. Antoine, Detroit, MI 48201, USA.
Department of Ophthalmology, Visual & Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Int Immunopharmacol. 2023 May;118:109953. doi: 10.1016/j.intimp.2023.109953. Epub 2023 Apr 3.
Microbial keratitis is a rapidly progressing, visually debilitating infection of the cornea that can lead to corneal scarring, endophthalmitis, and perforation. Corneal opacification or scarring, a complication of keratitis, is among the leading causes of legal blindness worldwide, second to cataracts.Pseudomonas aeruginosaandStaphylococcus aureusare the two bacteria most commonly associated with this type of infection. Risk factors include patients who are immunocompromised, those who have undergone refractive corneal surgery, and those with prior penetrating keratoplasty, as well as extended wear contact lens users. Current treatment of microbial keratitis primarily addresses the pathogen using antibiotics. Bacterial clearance is of utmost importance yet does not guarantee good visual outcome. Clinicians are often left to rely upon the eye's innate ability to heal itself, as there are limited options beyond antibiotics and corticosteroids for treating patients with corneal infection. Beyond antibiotics, agents in use, such as lubricating ointments, artificial tears, and anti-inflammatory drops, do not fully accommodate clinical needs and have many potential harmful complications. To this end, treatments are needed that both regulate the inflammatory response and promote corneal wound healing to resolve visual disturbances and improve quality of life. Thymosin beta 4 is a small, naturally occurring 43-amino-acid protein that promotes wound healing and reduces corneal inflammation and is currently in Phase 3 human clinical trials for dry eye disease. Our previous work has shown that topical Tβ4 as an adjunct to ciprofloxacin treatment reduces inflammatory mediators and inflammatory cell infiltrates (neutrophils/PMN and macrophages) while enhancing bacterial killing and wound healing pathway activation in an experimental model ofP. aeruginosa-induced keratitis. Adjunctive thymosin beta 4 treatment holds novel therapeutic potential to regulate and, optimally, resolve disease pathogenesis in the cornea and perhaps other infectious and immune-based inflammatory disease. We plan to establish the importance of thymosin beta 4 as a therapeutic agent in conjunction with antibiotics with high impact for immediate clinical development.
微生物角膜炎是一种迅速发展、严重影响视力的角膜感染，可导致角膜瘢痕、眼内炎和穿孔。角膜炎的并发症之一角膜混浊或瘢痕是全球导致法定失明的主要原因之一，仅次于白内障。绿脓假单胞菌和金黄色葡萄球菌是与这种类型感染最相关的两种细菌。风险因素包括免疫功能低下的患者、接受屈光性角膜手术的患者以及有穿透性角膜移植术史的患者，以及长期佩戴隐形眼镜的患者。目前微生物角膜炎的主要治疗方法是使用抗生素治疗病原体。细菌清除至关重要，但不能保证良好的视觉效果。临床医生往往只能依靠眼睛自身的愈合能力，因为除了抗生素和皮质类固醇之外，治疗角膜感染的患者的选择有限。除了抗生素之外，目前正在使用的药物，如润滑软膏、人工泪液和抗炎滴剂，都不能完全满足临床需求，而且存在许多潜在的有害并发症。为此，需要既能调节炎症反应，又能促进角膜伤口愈合的治疗方法，以解决视力障碍并提高生活质量。胸腺素β 4 是一种小的、天然存在的 43 个氨基酸的蛋白质，可促进伤口愈合，减少角膜炎症，目前正在进行治疗干眼症的 3 期人体临床试验。我们之前的工作表明，局部使用 Tβ4 作为环丙沙星治疗的辅助药物可减少炎症介质和炎症细胞浸润（中性粒细胞/PMN 和巨噬细胞），同时增强实验性绿脓假单胞菌诱导的角膜炎模型中的细菌杀伤和伤口愈合途径激活。辅助胸腺素β 4 治疗具有调节疾病发病机制的新的治疗潜力，并且在角膜和其他感染性和免疫性炎症性疾病中可能具有最佳的解决疾病发病机制的潜力。我们计划确定胸腺素β 4 作为与抗生素联合使用的治疗药物的重要性，这对立即进行临床开发具有重要意义。
