Advanced glycation end products can induce glial reaction and neuronal degeneration in retinal explants.
OBJECTIVE
Neuronal degeneration has been reported to occur in diabetic retinopathy before the onset of detectable microvascular abnormalities. To investigate whether advanced glycation end products (AGE) could be directly responsible for retinal neurodegeneration, retinal explants were incubated with glycated bovine serum albumin (BSA).


METHODS
Retinal explants obtained from non-diabetic adult rats were incubated 4 days with or without 200 mug/ml glycated BSA. Neural apoptosis was quantified by terminal dUTP nick end labelling (TUNEL) binding and immunostaining with anti-cleaved caspase-3 antibody. Expression of glial fibrillary acidic protein (GFAP) was localised by immunofluorescence.


RESULTS
TUNEL and cleaved caspase-3 positive cells increased significantly by 2.2-fold and 2.5-fold in retinal explants incubated in glycated BSA (p<0.05), respectively. The ganglion cell layer was the most sensitive retinal layer to the glycated BSA. Neuronal degeneration was confirmed by the increased GFAP labelling in Müller glial cells from retinal explants treated with glycated BSA.


CONCLUSIONS
These results suggest that AGE could induce retinal neurodegeneration in the absence of blood perfusion. Cells in the ganglion cell layer appeared to be the most sensitive as in diabetic retinopathy and its animal models. AGE toxicity could therefore contribute to the early pathological mechanisms of diabetic retinopathy.
Lecleire-Collet
A
A
INSERM-U592, Laboratory of Retinal Cellular and Molecular Physiopathology, Bâtiment Kourilsky, 184 rue du Faubourg Saint-Antoine, 75571 Paris cedex 12, France.
Tessier
L H
LH
Massin
P
P
Forster
V
V
Brasseur
G
G
Sahel
J A
JA
Picaud
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003930:Diabetic Retinopathy / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D020287:In Situ Nick-End Labeling; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D046509:Tissue Culture Techniques
D017127:Glycation End Products, Advanced