The AGE inhibitor pyridoxamine
inhibits development of retinopathy in experimental diabetes.
Stitt A, Gardiner TA, Alderson NL,
Canning P, Frizzell N, Duffy N, Boyle C, Januszewski AS, Chachich M,
Baynes JW, Thorpe SR, Anderson NL.
Department of Ophthalmology, Institute of
Clinical Science, The Royal Victoria Hospital, Queen's University of
Belfast, Belfast, Northern Ireland. a.stitt@qub.ac.uk
Diabetes. 2002 Sep;51(9):2826-32
Abstract
We examined the ability of
pyridoxamine (PM), an inhibitor of formation of advanced glycation end
products (AGEs) and lipoxidation end products (ALEs), to protect against
diabetes-induced retinal vascular lesions. The effects of pyridoxamine
were compared with the antioxidants vitamin E (VE) and R-alpha-lipoic
acid (LA) in streptozotocin-induced diabetic rats. Animals were given
either PM (1 g/l drinking water), Vitamin E (2,000 IU/kg diet), or
R-alpha-lipoic acid (0.05%/kg diet). After 29 weeks of diabetes, retinas
were examined for pathogenic changes, alterations in extracellular
matrix (ECM) gene expression, and accumulation of the immunoreactive
AGE/ALE N( epsilon )-(carboxymethyl)lysine (CML). Acellular capillaries
were increased more than threefold, accompanied by significant
upregulation of laminin immunoreactivity in the retinal
microvasculature. Diabetes also increased mRNA expression for
fibronectin (2-fold), collagen IV (1.6-fold), and laminin beta chain
(2.6-fold) in untreated diabetic rats compared with nondiabetic rats.
Pyridoxamine treatment protected against capillary drop-out and limited
laminin protein upregulation and ECM mRNA expression and the increase in
CML in the retinal vasculature. Vitamin E and R-alpha-lipoic acid failed
to protect against retinal capillary closure and had inconsistent
effects on diabetes-related upregulation of ECM mRNAs. These results
indicate that the AGE/ALE inhibitor pyridoxamine protected
against a range of pathological changes in the diabetic retina and
may be useful for treating diabetic retinopathy.
