A Novel Approach to Restore Sight after Corneal Chemical Injury

角膜化学损伤后恢复视力的新方法

基本信息

批准号：
10330580
负责人：
Haydee E.P. Bazan
金额：
$ 17.82万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-02-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10330580
关键词：
Alkalies Anti-Inflammatory Agents Arachidonic Acids Area Blindness Burn injury Cell Transplantation Cells Characteristics Chemical Burns Chemical Injury Chemicals Clinical Clinical Research Combined Modality Therapy Cornea Corneal Injury Corneal Stroma Corneal Ulcer Data Disease Emergency Situation Endothelium Epidermal Growth Factor Epithelial Experimental Models Extracellular Matrix Eye Eye Injuries Fibroblasts Flow Cytometry Future General Population Immunofluorescence Immunologic Infiltration Inflammation Inflammatory Inflammatory Response Injury Keratoplasty Laboratories Mesenchymal Stem Cells Metabolic Myofibroblast Necrosis Outcome Perforation Property Rattus Recurrence Reporting Research Stromal Cells T-Lymphocyte Testing Therapeutic Uses Time Tissues Transplantation Ulcer Visual Visual impairment Work base burn model cell stroma corneal burn corneal epithelium corneal repair cytokine improved in vivo innovation limbal lipid mediator lipoxin A4 macrophage melting neovascularization neutrophil novel novel strategies ocular surface preservation prevent protective effect reconstitution repaired sex sight restoration treatment response treatment strategy wound wound healing

项目摘要

Abstract Chemical burns to the eye are potentially blinding ocular injuries and constitute an ocular emergency requiring immediate assessment and initiation of treatment. They also constitute between 7-10% of the eye injuries in the general population. Out of all chemical injuries, alkali injuries are the most common and the most deleterious. Recurrent epithelial erosions, severe stromal inflammation, neovascularization, corneal ulceration and perforation are all prevalent complications of alkali burns. Currently, there is no successful treatment for severe damage to the cornea or to maintain corneal transparency. This proposal builds upon our previous findings that the lipid mediator, lipoxin A4 (LxA4), stimulates epithelial and endothelial wound healing, is involved in the reparative action of epidermal growth factor, and inhibits the inflammatory response stimulated after corneal injury. In addition, after severe alkali burn, there is a shortage of repair fibroblasts in ulcerated corneas, which is needed to synthesize components of the extracellular matrix (ECM) and to repair the stroma. The organizing hypothesis of the proposed research is that controlling the intense inflammatory response with LxA4 and reconstituting the ECM by stromal cell transplantation in a severe alkali burn model will avoid ulceration and neovascularization, thereby improving the visual outcome after severe ocular chemical injuries. We will test this hypothesis by pursuing two specific aims. In Specific Aim 1, we will use a severe rat alkali burn model (both sexes) to assess the action of LxA4 in in vivo clinical parameters and in inflammatory cytokines and conversion of macrophages type 1 (M1) to M2 by flow cytometry and immunofluorescence. In Specific Aim 2, we will investigate the anti-inflammatory action of the limbal stromal cells and combine treatment with LxA4 defined in Specific Aim 1 with cell transplantation of repair fibroblasts in the rat alkali burn model. We will determine clinical scores, presence of inflammatory cells, and ECM components after an early (3 days) and late (5 days) cell transplantation. The proposed studies, if successful, will target new approaches to investigate a novel treatment to control intense inflammation, to preserve the globe, and possibly, to restore transparency.

抽象的眼睛的化学烧伤可能会造成致盲性眼损伤，并构成眼部紧急情况，需要立即评估并开始治疗。它们还占眼睛损伤的 7-10% 一般人群。在所有化学伤害中，碱伤害是最常见和最有害的。复发性上皮糜烂、严重间质炎症、新生血管、角膜溃疡和穿孔是碱烧伤的常见并发症。目前，对于重症患者尚无成功的治疗方法损害角膜或保持角膜透明度。该提案建立在我们之前的发现之上：脂质介质脂氧素 A4 (LxA4) 可刺激上皮和内皮伤口愈合，参与表皮生长因子的修复作用，抑制角膜后刺激的炎症反应受伤。另外，严重碱烧伤后，溃疡角膜内修复成纤维细胞缺乏，合成细胞外基质（ECM）成分和修复基质所需的。组织者拟议研究的假设是用 LxA4 控制强烈的炎症反应在严重碱烧伤模型中通过基质细胞移植重建 ECM 将避免溃疡和新生血管形成，从而改善严重眼部化学物质后的视力结果受伤。我们将通过追求两个具体目标来检验这一假设。在具体目标 1 中，我们将使用一只严重的老鼠碱烧伤模型（男女）评估 LxA4 在体内临床参数和炎症中的作用通过流式细胞术和免疫荧光检测细胞因子以及 1 型巨噬细胞 (M1) 向 M2 的转化。在具体目标2，我们将研究角膜缘基质细胞的抗炎作用并结合治疗特定目标 1 中定义的 LxA4 在大鼠碱烧伤模型中进行修复成纤维细胞的细胞移植。我们将在早期（3 天）和晚期（5天）细胞移植。拟议的研究如果成功，将针对新的方法进行研究一种控制强烈炎症、保护地球并可能恢复透明度的新疗法。