Neutrophils Protect the Retina of the Injected Eye from Infection after Anterior Chamber Inoculation of HSV-1 in BALB/c Mice

• Published in: Investigative ophthalmology & visual science Vol. 49; no. 9; pp. 4018 - 4025
• Main Authors: Zheng, Mei, Fields, Mark A, Liu, Yi, Cathcart, Heather, Richter, Elizabeth, Atherton, Sally S
• Format: Journal Article
• Language: English
• Published: Rockville, MD ARVO 01.09.2008; Association for Research in Vision and Ophtalmology
• Subjects: Animals; Anterior Chamber - virology; Biological and medical sciences; Eye and associated structures. Visual pathways and centers. Vision; Female; Fundamental and applied biological sciences. Psychology; Herpes Simplex - prevention & control; Herpesvirus 1, Human - pathogenicity; Herpesvirus 1, Human - physiology; Medical sciences; Mice; Mice, Inbred BALB C; Neutrophils - physiology; Ophthalmology; Retina - physiology; Retinal Diseases - prevention & control; Retinal Diseases - virology; Vertebrates: nervous system and sense organs; Virus Replication; Herpesviridae; Alphaherpesvirinae; Rodentia; Ocular infection; Retina; Virus; Vertebrata; Inoculation; Mammalia; Mouse; Animal; Human herpesvirus 1; Anterior chamber; Neutrophil; Ophthalmology; Protection
• ISSN: 0146-0404; 1552-5783; 1552-5783
• DOI: 10.1167/iovs.08-1914

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.