thesis
Human herpes simplex virus keratitis: the pathogenesis revisted
- Publication date
- 20 June 2002
- Publisher
- The aim of this thesis is to elucidate pathogenic
mechanisms of different forms of
human HSV keratitis. HSV infection of the
corneal epithelium causes a classical dendritic
shaped lesion. Many studies could explain the
development and growth in dendritic keratitis,
but none of these found the anatomical substrate
for the linear branching pattern. The
most obvious explanation would be, that the
shape of dendritic ulcers corresponds with the
anatomical pattern of innervating nerves of
the cornea. In chapter 2 a relationship between
the shape of dendritic ulcers in infectious
epithelial keratitis and the subbasal nerve
plexus of the corneal epithelium is postulated.
Recurrence of HSV keratitis is a common
complication after PKP for corneal opacities
resulting from HSV infection. After PKP,
for reasons unrelated to HSV keratitis, epithelial
defects may still be caused by HSV. In
chapter 3 the incidence of newly acquired HSV
keratitis after PKP is determined and possible
contributing factors are assessed. Several possibilities
as to the origin of the infecting HSV
exist. These include reactivation oflatent virus
in the trigeminal ganglion, horizontal spread,
or transmission through the donor cornea. To
test the assumption of graft-to-host transmission
of HSV by PKP, surplus corneal material
was examined for the presence of HSV DNA. Because the amount of viral DNA available
could be very limited, a new method independent
of viral culture, was developed to
allow distinction between different virus
strains. The newly developed technique was
used to test our hypothesis that graft-to-host
transmission of HSV is possible. This new
method was used to determine the incidence
of HSV-1 superinfection in patients with
recurrent HSV keratitis.
Although HSK has been studied
extensively in the mouse model, it is not clear
what triggers the immune response and to
what extent the mouse data correlate with findings
in human keratitis. The most logical idea,
that virus-derived proteins are the eliciting factor
for the immune response, has been ruled
out in the experimental HSK mouse model.
Alternative sources of the keratogenic antigens,
like auto-antigens, have been suggested.
Data on the pathogenesis of human HSK are
limited. Therefore, in chapter 4 the antigenspecificity
of corneal T cells in HSK patients
was investigated. Besides this, corneas of
patients with HSK were examined for the
presence of corneal antigen reactive T cells
(auto-reactive T cells).
Chapter 5 provides a concise summary
of the data generated in the framework of this
thesis, and concludes with an overall discussion
of the data and their possible impact on
current ophthalmologic practice.