VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function

Vascular endothelial growth factor (VEGF) is a major therapeutic target for blood–retina barrier (BRB) breakdown in diabetic retinopathy (DR), age-related macular degeneration (AMD), and other hypoxic retinal vascular disorders. To determine whether VEGF is a direct regulator of retinal neuronal fun...

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Main Authors: Jianyan Hu, Meili Zhu, Dai Li, Qiang Wu, Yun-Zheng Le
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/11/7/988
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author Jianyan Hu
Meili Zhu
Dai Li
Qiang Wu
Yun-Zheng Le
author_facet Jianyan Hu
Meili Zhu
Dai Li
Qiang Wu
Yun-Zheng Le
author_sort Jianyan Hu
collection DOAJ
description Vascular endothelial growth factor (VEGF) is a major therapeutic target for blood–retina barrier (BRB) breakdown in diabetic retinopathy (DR), age-related macular degeneration (AMD), and other hypoxic retinal vascular disorders. To determine whether VEGF is a direct regulator of retinal neuronal function and its potential role in altering vision during the progression of DR, we examined the immediate impact of recombinant VEGF (rVEGF) on photoreceptor function with electroretinography in C57BL6 background wild-type (WT) and Akita spontaneous diabetic mice. Shortly after intravitreal injections, rVEGF caused a significant reduction of scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes in a dose-dependent manner in dark-adapted 1.5-mo-old WT mice. Compared with WT controls, 5-mo-old Akita spontaneous diabetic mice demonstrated a significant reduction in scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes. However, the effect of rVEGF altered photoreceptor function in WT controls was diminished in 5-mo-old Akita spontaneous diabetic mice. In conclusion, our results suggest that VEGF is a direct functional regulator of photoreceptors and VEGF up-regulation in DR is a contributing factor to diabetes-induced alteration of photoreceptor function. This information is critical to the understanding of the therapeutic effect and to the care of anti-VEGF drug-treated patients for BRB breakdown in DR, AMD, and other hypoxic retinal vascular disorders.
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spelling doaj.art-1425c73c96f84ad482a3bcf8f9d9bcf42023-11-22T03:18:20ZengMDPI AGBiomolecules2218-273X2021-07-0111798810.3390/biom11070988VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor FunctionJianyan Hu0Meili Zhu1Dai Li2Qiang Wu3Yun-Zheng Le4Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USASection of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USASection of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USADepartment of Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, ChinaSection of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAVascular endothelial growth factor (VEGF) is a major therapeutic target for blood–retina barrier (BRB) breakdown in diabetic retinopathy (DR), age-related macular degeneration (AMD), and other hypoxic retinal vascular disorders. To determine whether VEGF is a direct regulator of retinal neuronal function and its potential role in altering vision during the progression of DR, we examined the immediate impact of recombinant VEGF (rVEGF) on photoreceptor function with electroretinography in C57BL6 background wild-type (WT) and Akita spontaneous diabetic mice. Shortly after intravitreal injections, rVEGF caused a significant reduction of scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes in a dose-dependent manner in dark-adapted 1.5-mo-old WT mice. Compared with WT controls, 5-mo-old Akita spontaneous diabetic mice demonstrated a significant reduction in scotopic ERG a-wave and b-wave amplitudes and photopic ERG b-wave amplitudes. However, the effect of rVEGF altered photoreceptor function in WT controls was diminished in 5-mo-old Akita spontaneous diabetic mice. In conclusion, our results suggest that VEGF is a direct functional regulator of photoreceptors and VEGF up-regulation in DR is a contributing factor to diabetes-induced alteration of photoreceptor function. This information is critical to the understanding of the therapeutic effect and to the care of anti-VEGF drug-treated patients for BRB breakdown in DR, AMD, and other hypoxic retinal vascular disorders.https://www.mdpi.com/2218-273X/11/7/988VEGFphotoreceptorsneuronal functionERGdiabetic retinopathy
spellingShingle Jianyan Hu
Meili Zhu
Dai Li
Qiang Wu
Yun-Zheng Le
VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function
Biomolecules
VEGF
photoreceptors
neuronal function
ERG
diabetic retinopathy
title VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function
title_full VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function
title_fullStr VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function
title_full_unstemmed VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function
title_short VEGF as a Direct Functional Regulator of Photoreceptors and Contributing Factor to Diabetes-Induced Alteration of Photoreceptor Function
title_sort vegf as a direct functional regulator of photoreceptors and contributing factor to diabetes induced alteration of photoreceptor function
topic VEGF
photoreceptors
neuronal function
ERG
diabetic retinopathy
url https://www.mdpi.com/2218-273X/11/7/988
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