Se. Wilson et al., HERPES-SIMPLEX VIRUS TYPE-1 INFECTION OF CORNEAL EPITHELIAL-CELLS INDUCES APOPTOSIS OF THE UNDERLYING KERATOCYTES, Experimental Eye Research, 64(5), 1997, pp. 775-779
The purpose of this study was to determine whether primary corneal inf
ection with Herpes simplex virus (HSV)-1 induces keratocyte apoptosis
in the rabbit. New Zealand white rabbit eyes were inoculated with HSV-
1 strain 17 Syn(+). Rabbits that developed slit lamp signs of epitheli
al infection were killed between 12 and 120 hr post infection. One cor
nea of each animal was fresh-frozen for TUNEL assay to detect DNA frag
mentation in situ. The other cornea was fixed for transmission electro
n microscopy (TEM). Mechanical scrape wounded rabbit corneas were incl
uded as positive controls, DNA fragmentation consistent with apoptosis
was detected in anterior keratocytes of corneas at 18, 24, and 48 hr
after primary infection with HSV-1 and 2 hr after an epithelial scrape
, but not in unwounded control corneas. Electron microscopic evidence
of keratocyte apoptosis that included chromatin condensation, chromati
n fragmentation and cellular blebbing with formation of membrane bound
cell fragments was detected in mechanical scrape wounded corneas and
infected rabbit corneas at 12, 18, 24, 48, and 120 hr after infection,
but not in unwounded control corneas. This study suggests that anteri
or stromal keratocyte apoptosis occurs following primary HSV-1 infecti
on of the corneal epithelium, Previous studies have demonstrated that
corneal epithelial scrape wounds induce apoptosis in the underlying ke
ratocyte cells. We hypothesize that soluble mediators released by epit
helial injury mediate anterior keratocyte apoptosis and that one of th
e physiologic functions of this epithelial-stromal apoptosis system is
to limit viral extension. (C) 1997 Academic Press Limited.