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Aldose reductase inhibitor counteracts the enhanced expression of matrix metalloproteinase-10 and improves corneal wound healing in galactose-fed rats.
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We
investigated
the
effect
of
an
aldose
reductase
inhibitor
(
ARI
)
and
the
role
of
matrix
metalloproteinase
(
MMP
)
-
10
on
recovery
after
corneal
epithelium
removal
in
a
rat
diabetic
keratopathy
model
.
Three
-
week
-old
Sprague-
Dawley
rats
were
fed
the
following
diets
for
6
weeks
:
normal
MF
chow
(
MF
)
,
50
%
galactose
(
Gal
)
,
and
50
%
Gal
containing
0
.
01
%
ARI
(
Gal
+
ARI
)
.
The
corneal
epithelium
was
removed
using
n-heptanol
,
and
the
area
of
epithelial
defects
was
photographed
and
measured
every
24
h
.
Real-time
reverse
transcriptase
PCR
,
western
blotting
,
and
immunohistochemistry
were
used
to
determine
the
expression
profile
of
MMP-
10
and
integrin
α
3
.
Compared
to
the
MF
control
group
,
the
amount
of
galactitol
in
the
Gal
group
increased
approximately
200
-
fold
,
which
was
reduced
to
sevenfold
by
ARI
treatment
.
The
area
of
corneal
erosion
in
the
Gal
group
was
significantly
larger
than
in
the
MF
group
at
72
h
and
thereafter
(
p
<
0
.
01
,
unpaired
t
test
)
.
The
expression
level
of
MMP-
10
was
enhanced
at
both
the
protein
and
mRNA
levels
by
exposure
to
a
high
concentration
of
Gal
,
while
integrin
α
3
expression
decreased
at
the
protein
level
but
remained
unchanged
at
the
mRNA
level
.
Delayed
epithelial
wound
healing
and
alterations
in
the
expression
levels
of
MMP-
10
and
integrin
α
3
were
normalized
by
ARI
.
The
corneal
erosion
closure
rate
was
significantly
decreased
with
topical
recombinant
MMP-
10
.
These
studies
confirm
that
the
increased
expression
of
MMP-
10
induced
by
Gal
feeding
is
counteracted
by
ARI
treatment
and
suggest
a
role
of
MMP-
10
in
modulating
corneal
epithelial
wound
healing
.
