Weaver Cailey, Cyr Brianna, de Rivero Vaccari Juan Carlos, de Rivero Vaccari Juan Pablo
Department of Neurological Surgery and The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA.
DRV Ventures, LLC. Miami, FL, USA.
Transl Vis Sci Technol. 2020 Dec 17;9(13):27. doi: 10.1167/tvst.9.13.27. eCollection 2020 Dec.
Age-related macular degeneration (AMD) can result in severe vision loss and blurriness in the older population. The early and intermediate stages of AMD typically start without noticeable symptoms and can only be detected with a comprehensive eye exam. Because of the quiet onset of the disease, it is necessary to identify potential biomarkers to aid in the diagnosis, staging, and association with disease onset. Inflammasome signaling proteins are prominent biomarkers in the central nervous system, and the inflammasome has been shown to play a role in the innate inflammatory response in aging and AMD.
Serum from healthy controls and AMD patients were analyzed for the protein levels of Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), interleukin (IL)-18 and C-reactive protein (CRP) to determine cutoff points, positive and negative predictive values, and receiver operator characteristic curves, as well as univariate and multivariate linear and logistic regression models.
ASC, IL-18, and CRP were elevated in the serum of AMD patients when compared to healthy controls. The area under the curve (AUC) for ASC was 0.98 with a cutoff point of 365.6 pg/mL, whereas IL-18 had an AUC of 0.73 and a cutoff point of 242.4 pg/mL, and the AUC for CRP was 0.67 with a cutoff point of 8,684,152 pg/mL. Levels of IL-18 had a statistically significant linear correlation with that of ASC with an adjusted of 0.1906, indicating that 19% of IL-18 could be explained by ASC protein levels in serum. Moreover, a logistic regression model for the diagnosis of AMD consists of ASC and having a diagnosis of hypertension, indicating that these two factors (elevated levels of ASC and a diagnosis of hypertension [HTN]) are associated with the diagnosis of AMD.
ASC, IL-18, and CRP are elevated in patients with AMD, and the protein levels of IL-18 are partially the result of ASC protein expression. Moreover, elevated protein levels of ASC in serum and a diagnosis of HTN increase the odds of patients having a diagnosis of AMD.
Biomarkers of AMD may be used to monitor disease risk, response to treatment and disease progression.
年龄相关性黄斑变性（AMD）可导致老年人群严重视力丧失和视物模糊。AMD的早期和中期通常在没有明显症状的情况下开始，只能通过全面的眼科检查才能检测到。由于该疾病发病隐匿，因此有必要识别潜在的生物标志物，以辅助诊断、分期以及与疾病发病的关联研究。炎性小体信号蛋白是中枢神经系统中的重要生物标志物，并且已证明炎性小体在衰老和AMD的先天性炎症反应中起作用。
分析健康对照者和AMD患者血清中含半胱天冬酶募集结构域的凋亡相关斑点样蛋白（ASC）、白细胞介素（IL）-18和C反应蛋白（CRP）的蛋白水平，以确定临界值、阳性和阴性预测值、受试者工作特征曲线，以及单变量和多变量线性及逻辑回归模型。
与健康对照者相比，AMD患者血清中的ASC、IL-18和CRP升高。ASC的曲线下面积（AUC）为0.98，临界值为365.6 pg/mL，而IL-18的AUC为0.73，临界值为242.4 pg/mL，CRP的AUC为0.67，临界值为8,684,152 pg/mL。IL-18水平与ASC水平具有统计学意义的线性相关性，校正后的 为0.1906，表明血清中IL-18的19%可由ASC蛋白水平解释。此外，用于诊断AMD的逻辑回归模型包括ASC和患有高血压，表明这两个因素（ASC水平升高和高血压[HTN]诊断）与AMD诊断相关。
AMD患者的ASC、IL-18和CRP升高，IL-18的蛋白水平部分是ASC蛋白表达的结果。此外，血清中ASC蛋白水平升高和HTN诊断增加了患者被诊断为AMD的几率。
AMD的生物标志物可用于监测疾病风险、治疗反应和疾病进展。
