Mo Bin, Liu Wu, Yang Lin, Jiao Jian
Tongren Eye Center, Capital University of Medical Sciences, Beijing, China.
Zhonghua Yan Ke Za Zhi. 2007 Jan;43(1):49-54.
To determine whether nuclear transcription factor-kappaB (NF-kappaB) could modulate the expression of platelet-derived growth factor (PDGF) in rat retina induced by interleukin-1beta (IL-1beta) and studied the mechanism of inflammation-associated retinal diseases such as intraocular inflammation and proliferative vitreoretinopathy (PVR).
One hundred and twenty eight Sprague-Dawley rats were divided into A, B, C and D groups, the right eyes were served as experimental eyes, and the left eyes as normal controls. Animals received 2 intravitreal injections at 1 hour interval, which included BSS and BSS (group A); BSS and IL-1beta (group B); pyrrolidine dithiocarbamate (PDTC) and BSS (group C); PDTC and IL-1beta (group D). PDTC was one of special inhibitors of NF-kappaB activation. The Rat eyes were examined by slit-lamp before intravitreal injection, 4 and 24 hours after the injection. Degree of intraocular inflammation was graded using a scoring system. Rats were sacrificed 4 and 24 hours after the injection, the expressions of NF-kappaB and PDGF were detected by immunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR).
Four hours after the injection, eyes in group B, as compared with group D, showed more severe intraocular inflammatory signs such as photophobia, iris hyperemia, miosis, large amount of fibrin exudates and posterior synechia of iris. Histopathologic examination showed numerous inflammatory cells within the retinal parenchyma, vitreous and ciliary body. Positive cells of NF-kappaB and PDGF in group D, which could be observed within inner nuclear layer and ganglion cell layer, were obviously less than that in group B. The expression of PDGF mRNA was less in group D compared with group B (P < 0.05), however the expression of PDGF-A mRNA was significantly higher than PDGF-B in group B and group D (P < 0.05). Twenty four hours after the injection, intraocular inflammation alleviated gradually, the expression of PDGF and NF-kappaB decreased obviously.
These results suggest that NF-kappaB modulates the expression of PDGF in rat retina induced by IL-1beta. Upregulation of PDGF may play an important role in the occurrence of intraocular inflammation and the different isoform of PDGF may have different impact on various ocular diseases.
确定核转录因子-κB（NF-κB）是否能调节白细胞介素-1β（IL-1β）诱导的大鼠视网膜中血小板衍生生长因子（PDGF）的表达，并研究眼内炎症和增殖性玻璃体视网膜病变（PVR）等炎症相关视网膜疾病的发病机制。
将128只Sprague-Dawley大鼠分为A、B、C和D组，右眼作为实验眼，左眼作为正常对照。动物每隔1小时接受2次玻璃体腔内注射，分别为平衡盐溶液（BSS）和BSS（A组）；BSS和IL-1β（B组）；吡咯烷二硫代氨基甲酸盐（PDTC）和BSS（C组）；PDTC和IL-1β（D组）。PDTC是NF-κB激活的特异性抑制剂之一。在玻璃体腔内注射前、注射后4小时和24小时，用裂隙灯检查大鼠眼睛。使用评分系统对眼内炎症程度进行分级。在注射后4小时和24小时处死大鼠，通过免疫组织化学和逆转录聚合酶链反应（RT-PCR）检测NF-κB和PDGF的表达。
注射后4小时，与D组相比，B组眼睛出现更严重的眼内炎症体征，如畏光、虹膜充血、瞳孔缩小、大量纤维蛋白渗出和虹膜后粘连。组织病理学检查显示视网膜实质、玻璃体和睫状体中有大量炎症细胞。在D组的内核层和神经节细胞层内可观察到的NF-κB和PDGF阳性细胞明显少于B组。与B组相比，D组中PDGF mRNA的表达较少（P<0.05），然而在B组和D组中，PDGF-A mRNA的表达明显高于PDGF-B（P<0.05）。注射后24小时，眼内炎症逐渐减轻，PDGF和NF-κB的表达明显降低。
这些结果表明，NF-κB调节IL-1β诱导的大鼠视网膜中PDGF的表达。PDGF的上调可能在眼内炎症的发生中起重要作用，并且PDGF的不同异构体可能对各种眼部疾病有不同影响。
