Insulin like growth factor-1 works synergistically with dopamine to attenuate diabetic retinopathy by downregulating vascular endothelial growth factor - 20/04/22
, Seema Sen b , Tapas Chandra Nag c , Madhumita P. Ghosh a, ⁎ Abstract |
Aim |
Levels of Insulin-like growth factor-1 (IGF-1), a proangiogenic growth factor is elevated and dopamine downregulated in proliferative diabetic retinopathy (PDR). This study aims to investigate whether IGF-1 with dopamine can together modulate vascular endothelial growth factor (VEGF) to prevent proliferative diabetic retinopathy while also attenuating angiogenic effects of IGF-1.
Methods |
Effect of combination of levodopa L-Dopa with IGF-1 was tested on normal retinal pigment epithelium cells (ARPE-19) and human umbilical vein endothelial cells (HUVEC), followed by tube formation. Invivo analysis of anti-angiogenic potential assessed by chick chorioallantoic membrane (CAM) assay. Diabetes induction in wistar rats at two time points, 12 and 16 weeks, treated with L-Dopa+IGF-1 and analysed for morphological variations, serum and tissue dopamine levels, gene expression by real-time PCR and western blot assay.
Results |
L-Dopa+IGF-1 on ARPE-19 cells caused no toxicity and worked synergistically. Reduced number of vessels observed. Significant improvement in inner retina thickness (*p < 0.05) was observed when L-Dopa was given alone and/or with IGF-1. Dopamine levels improved significantly in both serum and tissue (*p < 0.05). Levels of VEGF and IGF-1 receptors reduced significantly in 12 weeks. Western studies suggest that L-Dopa+IGF-1 modulates its effects via Akt/ERK dependent pathway.
Conclusion |
First ever report on synergistic effect of L-Dopa+IGF-1 in a rat model of diabetic retinopathy. Even though the effect of L-Dopa in combination with IGF-1 is comparable to levels of L-Dopa alone, this study presents an interesting finding of neuroprotective function of IGF-1, which has been studied in disease models of Parkinson’s but not diabetes.
Il testo completo di questo articolo è disponibile in PDF.Graphical Abstract |
Highlights |
• | Dopamine levels decreased with progression of diabetic retinopathy. |
• | Intravitreal IGF-1 with L-Dopa improved dopamine levels in tissue significantly. |
• | DrD2 upregulation and VEGFR downregulation implies protective function of L-Dopa+IGF-1. |
• | ERK/Akt pathway is the underlying mechanism behind anti-angiogenic activity of L-Dopa+IGF-1. |
• | Apparent reduction in number of vessels as analysed by CAM assay. |
Keywords : Diabetic retinopathy, Dopamine, Insulin-like growth factor-1, Vascular dysfunction, Vascular endothelial growth factor, CAM assay
Mappa
Vol 149
Articolo 112868- maggio 2022 Ritorno al numero
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