过敏性结膜炎是导致眼部红肿(OR)的最常见原因。在这里,使用过敏性OR的动物模型,我们评估了局部阻断P物质(SP)治疗红眼的疗效。
在局部用组胺的豚鼠中诱导过敏性OR。使用特定的SP受体(神经激肽-1受体,NK1R)拮抗剂,L-703,606,通过局部应用在组胺滴注前10分钟或后10分钟。检查动物眼睛,并在OR诱导后长达60分钟拍摄一系列图像。使用定量眼部发红指数(ORI)分析发红的严重程度。在临床检查结束时,收集结膜组织进行结膜血管和浸润嗜酸性粒细胞和中性粒细胞的组织学检查.此外,在泪液中定量SP浓度,并在结膜组织中评估炎性细胞因子的表达水平。
局部应用组胺成功诱发红眼,观察期间ORI显著增加,峰值在10分钟,随着泪液中SP水平的显着增加。使用L-703,606的局部治疗,在使用组胺之前或在ORI峰值时,有效降低ORI,抑制结膜血管扩张,随着嗜酸性粒细胞和中性粒细胞浸润的减少,和炎症细胞因子在结膜中的表达,以及降低眼泪中的SP水平。
SP的局部阻断通过抑制血管扩张和过敏性炎症有效地预防和治疗与过敏相关的眼部发红。
Allergic conjunctivitis is the most common cause leading to ocular redness (OR). Herein, using an animal model of allergic OR, we evaluated the therapeutic efficacy of topical blockade of substance P (SP) in treating red eye.
Allergic OR was induced in guinea pigs with topical histamine. Ocular SP was blocked using a specific SP receptor (neurokinin-1 receptor, NK1R) antagonist, L-703,606, via topical application 10 min before or 10 min after histamine instillation. Animal eyes were examined and a series of images were taken for up to 60 min post-OR induction. The severity of redness was analyzed using the quantitative ocular redness index (ORI). At the end of clinical examination, conjunctival tissues were collected for histological examination of conjunctival blood vessels and infiltrating eosinophils and neutrophils. In addition, SP concentration was quantified in the tear fluid and expression levels of inflammatory cytokines were assessed in the conjunctival tissues.
Topical histamine application successfully induced red eye, evidenced by the significantly increased ORI during the observation period, with peak values at 10 min, along with significantly increased levels of SP in the tears. Topical treatment with L-703,606, either before histamine application or at the time of peak ORI, effectively reduced ORI and suppressed conjunctival blood vessel dilation, along with decreased eosinophil and neutrophil infiltration, and inflammatory cytokine expression in the conjunctiva, as well as reduced SP levels in the tears.
Topical blockade of SP effectively prevents and treats allergy-related ocular redness by suppressing blood vessel dilation and allergic inflammation.