Pyridoxamine
Protects Against Diabetic Retinopathy
Pyridoxamine,
an inhibitor of advanced glycation end products (AGEs), appears to
protect against pathological changes in the retinas of diabetic rats
and may be a new treatment for diabetic retinopathy.
"This
preclinical study is a demonstration of efficacy of pyridoxamine in
preventing aspects of diabetic retinopathy in an experimental animal
model," Dr. Alan Stitt from Royal Victoria Hospital, Belfast,
Northern Ireland, told Reuters Health.
Dr.
Stitt and colleagues compared the effects of pyridoxamine with the
antioxidants vitamin E and R-alpha-lipoic acid in streptozotocin-induced
diabetic rats, according to their report, published in the September
issue of Diabetes.
The
researchers gave the rats pyridoxamine 1g/L drinking water or 2,000 IU
of vitamin E per kilogram diet or 0.05% per kilogram diet of R-alpha-lipoic
acid.
"The
approach we used looked at physical death of retinal capillaries
during diabetes and some pathophysiological measures," Dr. Stitt
said. The investigators examined the retinas of the animals after 29
days, looking for pathogenic changes and alterations in extracellular
matrix gene expression and accumulation of immunoreactive
carboxymethyl lysine from AGE and lipoxidation end products.
Compared
with untreated rats, the pyridoxamine-treated animals were protected
from capillary death, limited laminin protein up-regulation,
extra-cellular matrix mRNA expression and an increase in carboxymethyl
lysine in the retinal vessels.
"Interestingly,
co-study of antioxidants did not have anywhere near the same effect in
these animals," Dr. Stitt said. Rats treated with vitamin E or
R-alpha-lipoic acid show no protection against retinal capillary
closure and showed inconsistent effects on diabetes-related
up-regulation of extracellular matrix mRNAs, the researchers found.
"This
study shows that AGEs probably play an important role in diabetic
retinopathy, although to be definitive about this there would need to
be more studies conducted," Dr. Stitt said.
"This
finding is important because diabetic retinopathy is a major cause of
blindness in developed countries and there are no real therapeutic
options for diabetic patients, beyond pan-retinal laser
photocoagulation, which is very destructive of healthy retina and is
only effective in the late stages," he added. "Further
development of this therapeutic approach, or closely related
strategies, have potential for preventing retinopathy in diabetic
patients."
BioStratum,
Inc., in Durham, North Carolina, is developing pyridoxamine as a drug
called Pyridorin, Dr. Stitt noted. Diabetes
2002;51:2826-2832.
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FACT
Type
2 diabetes can be predicted by increases in microalbuminura
( a measure of protein in the urine).
In addition, the association between increased protein in the
urine and rising blood-glucose levels was present even when
blood-glucose levels were below those used to diagnose diabetes.
Diabetes Care, June 2002
