de Gracia Pablo, Gallego Beatriz I, Rojas Blanca, Ramírez Ana I, de Hoz Rosa, Salazar Juan J, Triviño Alberto, Ramírez José M
Department of Neurobiology, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States of America.
Instituto de Investigaciones Oftalmológicas Ramón Castroviejo, Universidad Complutense de Madrid, Madrid, Spain.
PLoS One. 2015 Nov 18;10(11):e0143278. doi: 10.1371/journal.pone.0143278. eCollection 2015.
Proliferation of microglial cells has been considered a sign of glial activation and a hallmark of ongoing neurodegenerative diseases. Microglia activation is analyzed in animal models of different eye diseases. Numerous retinal samples are required for each of these studies to obtain relevant data of statistical significance. Because manual quantification of microglial cells is time consuming, the aim of this study was develop an algorithm for automatic identification of retinal microglia. Two groups of adult male Swiss mice were used: age-matched controls (naïve, n = 6) and mice subjected to unilateral laser-induced ocular hypertension (lasered; n = 9). In the latter group, both hypertensive eyes and contralateral untreated retinas were analyzed. Retinal whole mounts were immunostained with anti Iba-1 for detecting microglial cell populations. A new algorithm was developed in MATLAB for microglial quantification; it enabled the quantification of microglial cells in the inner and outer plexiform layers and evaluates the area of the retina occupied by Iba-1+ microglia in the nerve fiber-ganglion cell layer. The automatic method was applied to a set of 6,000 images. To validate the algorithm, mouse retinas were evaluated both manually and computationally; the program correctly assessed the number of cells (Pearson correlation R = 0.94 and R = 0.98 for the inner and outer plexiform layers respectively). Statistically significant differences in glial cell number were found between naïve, lasered eyes and contralateral eyes (P<0.05, naïve versus contralateral eyes; P<0.001, naïve versus lasered eyes and contralateral versus lasered eyes). The algorithm developed is a reliable and fast tool that can evaluate the number of microglial cells in naïve mouse retinas and in retinas exhibiting proliferation. The implementation of this new automatic method can enable faster quantification of microglial cells in retinal pathologies.
小胶质细胞的增殖被认为是胶质细胞激活的标志以及进行性神经退行性疾病的一个特征。在不同眼部疾病的动物模型中分析小胶质细胞激活情况。为了获得具有统计学意义的相关数据,每项此类研究都需要大量视网膜样本。由于手动定量小胶质细胞耗时费力,本研究的目的是开发一种用于自动识别视网膜小胶质细胞的算法。使用了两组成年雄性瑞士小鼠:年龄匹配的对照组(未处理,n = 6)和单侧激光诱导性高眼压小鼠(激光处理组;n = 9)。在后一组中,对高血压眼和对侧未处理的视网膜都进行了分析。用抗Iba-1对视网膜全层进行免疫染色以检测小胶质细胞群体。在MATLAB中开发了一种用于小胶质细胞定量的新算法;它能够对内外丛状层中的小胶质细胞进行定量,并评估神经纤维-神经节细胞层中Iba-1+小胶质细胞占据的视网膜面积。将该自动方法应用于一组6000张图像。为了验证该算法,对小鼠视网膜进行了手动和计算机评估;该程序正确评估了细胞数量(内外丛状层的皮尔逊相关系数R分别为0.94和0.98)。在未处理组、激光处理眼和对侧眼之间发现胶质细胞数量存在统计学显著差异(未处理组与对侧眼相比,P<0.05;未处理组与激光处理眼以及对侧眼与激光处理眼相比,P<0.001)。所开发的算法是一种可靠且快速的工具,可用于评估未处理小鼠视网膜以及呈现增殖的视网膜中的小胶质细胞数量。这种新自动方法的应用能够在视网膜病变中更快地定量小胶质细胞。