Recurrent herpes simplex after corneal transplantation in rats.
OBJECTIVE
To ascertain the effect of trauma from surgery and rejection on the incidence and timing of recurrent herpes simplex virus (HSV) disease after corneal transplantation. To locate virus antigen and identify cells of the immune system infiltrating corneas with recurrent disease.


METHODS
PVG rats were inoculated on the cornea with HSV-1 McKrae. Recurrent disease was induced either by ultraviolet (UV)-irradiation of the cornea or by corneal transplantation. After corneal transplantation, animals shedding virus in the tear film were killed on days 1 to 4 of shedding. Eyes were fixed, embedded, sectioned, and stained for virus antigens, infiltrating cells, major histocompatibility complex class II, and adhesion molecule molecule expression.


RESULTS
In the first 15 days after corneal transplantation, 8 of 91 rats shed virus, and between days 16 and 30, an additional 3 of 60 rats shed virus (12% of total rats, comparable to the percent that shed after UV irradiation). Shedding sometimes was accompanied by punctate epithelial lesions in the recipient cornea and stromal opacity. The rejection process itself did not induce or exacerbate recurrent disease. In all corneas examined from eyes that shed virus, antigen was found in several locations at the graft-host junction, sometimes in the absence of clinical signs of disease, and frequently it extended through the stroma to the endothelium. Granulocytes were the main infiltrating cell in areas of virus antigen.


CONCLUSIONS
Corneal transplantation trauma is a stimulus to recurrent disease of similar potency to UV irradiation. The graft-host junction is an area in which virus spreads easily and can reach the endothelium readily. In humans, the incidence of recurrent disease at this location may be greater than has been recognized.
Nicholls
S M
SM
Department of Ophthalmology, School of Medical Sciences, Bristol, United Kingdom.
Shimeld
C
C
Easty
D L
DL
Hill
T J
TJ
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D003315:Cornea / Q000737:chemistry / Q000473:pathology / Q000821:virology; D016039:Corneal Transplantation / Q000009:adverse effects*; D005260:Female; D006084:Graft Rejection / Q000209:etiology / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000302:isolation & purification / Q000502:physiology; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007124:Immunoenzyme Techniques; D016849:Keratitis, Herpetic / Q000209:etiology* / Q000473:pathology / Q000821:virology; D051381:Rats; D011917:Rats, Inbred Lew; D012008:Recurrence; D013047:Specific Pathogen-Free Organisms; D014466:Ultraviolet Rays; D014775:Virus Activation; D017201:Virus Shedding
D000956:Antigens, Viral; D015815:Cell Adhesion Molecules; D000949:Histocompatibility Antigens Class II