Zheng Mei, Fields Mark A, Liu Yi, Cathcart Heather, Richter Elizabeth, Atherton Sally S
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia, USA.
Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4018-25. doi: 10.1167/iovs.08-1914. Epub 2008 May 16.
To determine whether infiltrating polymorphonuclear leukocytes PMNs play a role in preventing early direct anterior-to-posterior spread of herpes simplex virus (HSV)-1 and/or in preventing the spread of HSV-1 from the brain back to the retina of the injected eye after anterior chamber (AC) inoculation.
BALB/c mice were treated with monoclonal antibody RB6-8C5 (Gr-1) against PMNs or control IgG and inoculated with HSV-1.
In Gr-1-treated mice, PMNs were depleted in the peripheral blood and in the HSV-1-infected eye. More virus (2-3 logs) was recovered from the inoculated eye of Gr-1 antibody-treated mice than from control mice. Immunohistochemistry revealed disseminated virus-infected cells in the junction between the anterior and the posterior segment and also in the posterior segment of the HSV-1-inoculated eye in Gr-1-treated mice. In control IgG-treated mice, virus-infected cells were observed only within the AC. More virus (3 logs) was recovered from the contralateral suprachiasmatic nucleus (SCN), and increased virus staining was observed in the ipsilateral optic nerve of Gr-1-treated mice compared with control mice. In Gr-1-treated mice, the central retina was virus-infected in a patchy fashion beginning on day 7 post infection (pi), and the infection progressed to involve the entire retina.
Since both direct anterior-to-posterior spread of virus and spread via the optic nerve occurred in PMN-depleted mice, these results suggest that PMNs play an important role both in limiting intraocular spread of virus in the injected eye and in controlling spread of the virus from the brain into the optic nerve and retina of the injected eye.
确定浸润的多形核白细胞（PMN）是否在预防单纯疱疹病毒1型（HSV-1）早期从前向后直接扩散以及/或者在预防前房（AC）接种后HSV-1从脑向注射眼视网膜逆向扩散中发挥作用。
用抗PMN的单克隆抗体RB6-8C5（Gr-1）或对照IgG处理BALB/c小鼠，然后接种HSV-1。
在接受Gr-1处理的小鼠中，外周血和感染HSV-1的眼中PMN减少。与对照小鼠相比，从接受Gr-1抗体处理的小鼠接种眼中回收的病毒更多（2 - 3个对数）。免疫组织化学显示，在接受Gr-1处理的小鼠中，HSV-1接种眼的前后段交界处以及后段有散在的病毒感染细胞。在接受对照IgG处理的小鼠中，仅在前房内观察到病毒感染细胞。与对照小鼠相比，接受Gr-1处理的小鼠对侧视交叉上核（SCN）中回收的病毒更多（3个对数），且同侧视神经中病毒染色增加。在接受Gr-1处理的小鼠中，感染后第7天开始中央视网膜出现散在的病毒感染，感染逐渐发展至累及整个视网膜。
由于在PMN缺失的小鼠中既发生了病毒从前向后的直接扩散，也发生了通过视神经的扩散，这些结果表明PMN在限制注射眼内病毒的眼内扩散以及控制病毒从脑向注射眼的视神经和视网膜扩散中均发挥重要作用。
