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Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto; Effect Of Low Dose Advanced Glycation End-products On Neurite Regeneration In Adult Rat Retinas And Regenerative Effects Of Nt-4 In Advanced Glycation End-products Exposed Retinas. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3481.
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© ARVO (1962-2015); The Authors (2016-present)
To determine the effect of low dose advanced glycation end-products (AGE) on neurite regeneration in isolated rat retinas and the regenerative effect of neurotrophin-4 (NT-4) in AGE exposed retinas.
All of the procedures were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Retinal explants of 4 adult SD rats were studied. The explants were three-dimensionally cultured in collagen gel and were incubated either in; 1) serum free control culture media, 2) 10 μg/ml glucose-AGE-BSA media, 3) 10 μg/ml glycolaldehyde-AGE-BSA media, 4) 10 μg/ml glyceraldehyde-AGE-BSA media, 5) 10 μg/ml glucose-AGE-BSA+100ng/ml NT-4 media, 6) 10 μg/ml glycolaldehyde-AGE-BSA+100ng/ml NT-4 media, or 7) 10 μg/ml glyceraldehyde-AGE-BSA+100 ng/ml NT-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted under a phase-contrast microscope. ANOVA with Scheffe’s F test was performed to determine whether the number of neuritis were significantly different among the different culture conditions.
In retinas incubated with glucose-AGE-BSA, glycolaldehyde-AGE-BSA, and glyceraldehyde-AGE-BSA, the number of regenerating neurites was significantly fewer than in retinas without AGE (68.56±4.68/mm2 vs. 30.81±4.50/mm2; P=0.0033, 68.56±4.68/mm2 vs. 31.25±5.71/mm2; P=0.0044, 68.56±4.68/mm2 vs. 31.75±3.68/mm2; P=0.0238). In AGE exposed retinas supplemented with NT-4, the numbers of regenerating neuritis were significantly higher than in glucose-AGE-BSA without NT-4 (210.00±26.25/mm2 vs. 30.81±4.50/mm2; P<0.0001), in glycolaldehyde-AGE-BSA without NT-4 (193.75±24.06/mm2 vs. 31.25±5.71/mm2; P<0.0001), and in glyceraldehyde-AGE-BSA without NT-4 (168.75±10.56/mm2 vs. 31.75±3.68/mm2; P<0.0001).
Low dose of AGE impedes neurite regeneration in adult rat retinas. This is important in relation to the pathogenesis of several retinal diseases that form and accumulate AGE such as diabetic retinopathy and other age-related neuronal diseases. NT-4 significantly enhances neurite regeneration in retinas exposed to AGE.
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