June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Loss of Retinal Arteriole Smooth Muscle Cell Coverage: A Potential Consequence of Altered Caveolin-1 Dependent Metabolism
Author Affiliations & Notes
  • Jennifer Ballheim
    Ophthalmology/Dean McGee Eye Institute, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Atul Pranay
    Aging and Metabolism Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States
  • Albert Batushansky
    Aging and Metabolism Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States
  • Elizabeth Hargis
    Ophthalmology/Dean McGee Eye Institute, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Tim Griffin
    Aging and Metabolism Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States
  • Jami Gurley
    Ophthalmology/Dean McGee Eye Institute, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
    Physiology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Jennifer Ballheim None; Atul Pranay None; Albert Batushansky None; Elizabeth Hargis None; Tim Griffin None; Jami Gurley None
  • Footnotes
    Support  American Heart Association; Presbyterian Health Foundation; NIH P30EY021725; Research to Prevent Blindness, Inc.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1233. doi:
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      Jennifer Ballheim, Atul Pranay, Albert Batushansky, Elizabeth Hargis, Tim Griffin, Jami Gurley; Loss of Retinal Arteriole Smooth Muscle Cell Coverage: A Potential Consequence of Altered Caveolin-1 Dependent Metabolism. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1233.

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

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Abstract

Purpose : Retinal vessel dysfunction results in ocular diseases, including diabetic retinopathy (DR). Understanding the mechanism behind changes in vascular physiology will lead to novel treatments for early DR pathogenesis. A primary feature of early-stage DR in humans is retinal arteriole smooth muscle cell (SMC) loss, which is recapitulated in endothelial cell Caveolin-1 knockout (EC Cav1-KO) mice. Studies have established that Cav1 plays an important role in EC metabolism. However, the relationship among DR, EC-Cav1, and retinal metabolism as it relates to arteriole SMC loss remains unclear. The overarching goal of this study is to test the hypothesis that EC-Cav1 modulates metabolic pathways that impact SMC maintenance.

Methods : EC-specific Cav1 KO mice were generated via deletion of the Cav1 floxed gene using Tie2-specific Cre recombination. GC-MS metabolic profiling and multivariate data analysis were used to assess EC-Cav1 depletion effect on whole retinal metabolites. Bioluminescent determination of ATP was used to assess EC-Cav1 depletion effect on whole retinal energy status. Western Blot analysis was used to assess EC-Cav1 depletion effect on whole retinal metabolic protein expression levels.

Results : EC-Cav1 depletion reduced whole retinal glycolytic and amino acid levels, while ATP levels remained unchanged. Voltage-dependent anion channel 1 (VDAC-1) is known to be the primary means for metabolite diffusion across the mitochondrial membrane. EC-specific deletion of Cav1 reduced whole retinal VDAC-1 protein expression by 41% compared to wild-type mice (p ≤ 0.05, n = 3-5). Retinal mitochondrial proteins pyruvate dehydrogenase (PDH), 60-kDa heat shock protein (HSP60), and succinate dehydrogenase (SDHA) remained unchanged in EC-Cav1 KO mice.

Conclusions : Our results support that EC-Cav1 plays a major role in retinal tissue. Whole retinal metabolomic profile depletion suggests that EC-Cav1 has an extensive impact on retinal metabolic regulation. The reduction in VDAC-1 suggests that EC-Cav1 plays a role in mitochondrial function or number in retinal tissues. Future studies will focus on identifying specific EC-Cav1-dependent metabolic pathways that impact retinal vessel integrity, whole retinal tissue metabolism, and retinal vascular disease.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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