2001
Ocular Microbiology and Immunology Group, Abstract 17
OMIG
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Reduction of Corneal Allorejection Mediated
by Alpha-Melanocyte Stimulating Hormone Treatment
P. Hamrah, Z. Haskova, Q. Zhang, A.W. Taylor, B. Ksander and R.
Dana
Schepens Eye Research Institute, Department of Ophthalmology, Harvard
Medical School, Boston MA
Purpose: To determine the possible role of a-MSH on orthotopic corneal
allograft survival and the mechanisms by which it may influence
graft outcome.
Methods: Orthotopic corneal allograft
transplantation was performed with different strains of mice. Recipients
either received a sham injection or were treated with 1.2 µg
subconjunctival injections of a-MSH twice weekly. Grafts were followed
for 70 days and graft inflammation/opacification was compared between
the two groups in a masked fashion. Additionally, graft infiltration
was determined in both groups at days 7 and 14. Allospecific delayed
type hypersensitivity (DTH) was compared among the groups 3 weeks
post transplantation. Additionally, ocular gene expression of select
inflammatory cytokines was evaluated at different time points by
the ribonuclease protection assay.
Results: Corneal allografts in
a-MSH-treated recipients showed an increase in graft survival as
compared to untreated hosts. Over 70% of allografts in a-MSH treated
hosts survived at 70 days, compared to less than 50% in the untreated
group. Graft infiltration by mononuclear and polymorphonuclear (PMN)
cells was significantly decreased in a-MSH treated mice compared
to untreated hosts (P<0.05). Moreover, DTH results and cytokine
expression (including Interferon-g and Interleukin-2) were significantly
reduced in a-MSH treated mice as compared to untreated recipients.
Conclusion: We provide for the
first time, in vivo evidence that treatment with the neuropeptide
a-MSH reduces allorejection of corneal transplants.
This study was
supported in part by Alcon Laboratories, INC.
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