June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
VEGF as a direct regulator of photoreceptor function and a major contributing factor for altering photoreceptor function in diabetes and hypoxia
Author Affiliations & Notes
  • Yun-Zheng Le
    Medicine, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma, United States
  • Jianyan Hu
    Medicine, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma, United States
    Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
  • Meili Zhu
    Medicine, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma, United States
  • Dai Li
    Medicine, University of Oklahoma Health Sciences Center, Oklahoma city, Oklahoma, United States
    School of Optometry, Hubei University of Science and Technology, Xianning, China
  • Qiang Wu
    Ophthalmology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
  • Footnotes
    Commercial Relationships   Yun-Zheng Le None; Jianyan Hu None; Meili Zhu None; Dai Li None; Qiang Wu None
  • Footnotes
    Support  NIH grants R01EY26970, R01EY20900, P30EY021725, P30GM122744, grants from Re-search to Prevent Blindness, Oklahoma Center for the Advancement of Science and Technology (HR20-065), Oklahoma Center for Adult Stem Cell Research (a program of TSET), Presbyterian Health Foundation, grants 81070738 and 81300775 from National Natural Science Foundation of China, and endowed endowments Chair Funds from Choctaw Nation and Mr. Harold Hamm
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4111 – F0348. doi:
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      Yun-Zheng Le, Jianyan Hu, Meili Zhu, Dai Li, Qiang Wu; VEGF as a direct regulator of photoreceptor function and a major contributing factor for altering photoreceptor function in diabetes and hypoxia. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4111 – F0348.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Vascular endothelial growth factor (VEGF or VEGF-A), a major therapeutic target for blood-retina barrier breakdown (BRB) in diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD), has been shown to act as a direct functional regulator for peripheral and central nervous system (CNS) neurons. The purpose of this study was to determine whether VEGF is a direct regulator of photoreceptor function and its potential role in altering vision during the progression of DR, AMD, and other hypoxic retinal BRB diseases.

Methods : For this study, we developed a procedure to measure the direct effect of VEGF on photoreceptor function with electroretinography (ERG). Overnight dark-adapted wild-type (WT) mice were injected with recombinant VEGF (rVEGF) intravitreally under long-wavelength illumination. Retinal function in these mice was examined with scotopic and photopic electroretinography ERG immediately after intravitreal rVEGF delivery. Diabetes- or hypoxia-induced alteration of photoreceptor function was examined with Akita diabetic mice or hypoxic mice immediately after injected with rVEGF or vehicle.

Results : In dark-adapted WT mice, 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. However, the effect of rVEGF on the alteration of ERG amplitudes was nullified in 5-mo-old Akita diabetic mice in which a higher level of VEGF was present in photoreceptors. A similar result was also observed in 1.5 mo-old hypoxic mice generated by placing the animals with 7% oxygen for 5 days.

Conclusions : Our results suggest that VEGF is a direct functional regulator for photoreceptors and a contributing factor to the loss of photoreceptor function in diabetes and hypoxia (retinal environment in AMD). As VEGF is a major therapeutic target for BRB breakdown in DR, AMD, and other hypoxic retinal BRB diseases, our work provides the mechanistic insights for the therapeutic effects on visual acuity and for the care of anti-VEGF drug treated patients.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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