Article Text
Abstract
Background/aims: 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 μg/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.
Conclusion: 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.
- AGE, advanced glycation end products
- BSA, bovine serum albumin
- DAPI, diamidino-phenyl-indole
- DR, diabetic retinopathy
- GCL, ganglion cell layer
- GFAP, glial fibrillary acidic protein
- GLAST, l-glutamate/l-aspartate transporter antibody
- INL, inner nuclear layer
- ONL, outer nuclear layer
- OPL, outer plexiform layer
- RAGE, AGE receptor
- RPE, retinal pigment epithelium
- TUNEL, terminal dUTP nick end labelling
- VEGF, vascular endothelium growth factor
- advanced glycation end products
- diabetic retinopathy
- glial reaction
- neuronal apoptosis
- rat
- AGE, advanced glycation end products
- BSA, bovine serum albumin
- DAPI, diamidino-phenyl-indole
- DR, diabetic retinopathy
- GCL, ganglion cell layer
- GFAP, glial fibrillary acidic protein
- GLAST, l-glutamate/l-aspartate transporter antibody
- INL, inner nuclear layer
- ONL, outer nuclear layer
- OPL, outer plexiform layer
- RAGE, AGE receptor
- RPE, retinal pigment epithelium
- TUNEL, terminal dUTP nick end labelling
- VEGF, vascular endothelium growth factor
- advanced glycation end products
- diabetic retinopathy
- glial reaction
- neuronal apoptosis
- rat
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- AGE, advanced glycation end products
- BSA, bovine serum albumin
- DAPI, diamidino-phenyl-indole
- DR, diabetic retinopathy
- GCL, ganglion cell layer
- GFAP, glial fibrillary acidic protein
- GLAST, l-glutamate/l-aspartate transporter antibody
- INL, inner nuclear layer
- ONL, outer nuclear layer
- OPL, outer plexiform layer
- RAGE, AGE receptor
- RPE, retinal pigment epithelium
- TUNEL, terminal dUTP nick end labelling
- VEGF, vascular endothelium growth factor
- advanced glycation end products
- diabetic retinopathy
- glial reaction
- neuronal apoptosis
- rat
- AGE, advanced glycation end products
- BSA, bovine serum albumin
- DAPI, diamidino-phenyl-indole
- DR, diabetic retinopathy
- GCL, ganglion cell layer
- GFAP, glial fibrillary acidic protein
- GLAST, l-glutamate/l-aspartate transporter antibody
- INL, inner nuclear layer
- ONL, outer nuclear layer
- OPL, outer plexiform layer
- RAGE, AGE receptor
- RPE, retinal pigment epithelium
- TUNEL, terminal dUTP nick end labelling
- VEGF, vascular endothelium growth factor
- advanced glycation end products
- diabetic retinopathy
- glial reaction
- neuronal apoptosis
- rat