July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Reduced Retinal Arteriole Smooth Muscle Coverage with Age: A Potential Caveolin-1 Dependent Mechanism of Altered Retinal Metabolism
Author Affiliations & Notes
  • Jami Gurley
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Alaina Reagan
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Nick Standifer
    University of Oklahoma, Norman, Oklahoma, United States
  • Michael Stout
    Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Michael H Elliott
    Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Jami Gurley, None; Alaina Reagan, None; Nick Standifer, None; Michael Stout, None; Michael Elliott, None
  • Footnotes
    Support  OCAST HF018-008; R01 EY019494; P30 EY021725; Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 1632. doi:
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      Jami Gurley, Alaina Reagan, Nick Standifer, Michael Stout, Michael H Elliott; Reduced Retinal Arteriole Smooth Muscle Coverage with Age: A Potential Caveolin-1 Dependent Mechanism of Altered Retinal Metabolism. Invest. Ophthalmol. Vis. Sci. 2019;60(9):1632.

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

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Abstract

Purpose : Aging leads to changes in retinal vascular structure and physiology and is associated with development of ocular pathologies (e.g., age-related macular degeneration, diabetic retinopathy, and glaucoma). Changes in retinal vascular structure and function are not well understood, but include a reduction in smooth muscle cell (SMC) coverage of retinal vascular endothelium. We have also observed this phenotype in Caveolin-1 knockout (Cav1-KO) mice. The purpose of this study was to investigate whether the SMC coverage phenotype observed in Cav1-KO and aged mice is due to endothelial cell (EC)- and/or smooth muscle cell (SMC)-specific Cav1 depletion, and to examine potential physiological mechanisms responsible for SMC loss that occurs with aging and retinal disease.

Methods : EC- and SMC-specific Cav1 KO mice were generated via deletion of the Cav1 floxed gene using either Tie2- or SM22-specific Cre recombination. Vascular SMCs were identified via confocal laser scanning microscopy of superficial arteriole SMC-specific (α-smooth muscle actin) staining of whole retinal flatmounts. SMC vessel coverage area and number of SMC “gaps” were determined by ImageJ analysis (Reagan et al. 2018). Retinas were co-stained with EC-specific CD31 and Cav1 antibodies. We also assessed SMC coverage in HFD-fed and leptin-deficient (Ob/Ob) mice.

Results : EC-specific Cav1 deletion resulted in an increased number of SMC “gaps” (p<0.001), but did not significantly affect total SMC area when compared to wildtype controls. There was no change observed in young SMC-Cav1 KO, suggesting that EC-Cav1 (but not SMC-Cav1) is responsible for SMC loss. HFD provided late in life did not exacerbate age-associated SMC loss (1-Way ANOVA, young vs. old p<0.001; old vs. old/HFD n.s.). However, Ob/Ob mice showed reduced SMC coverage (p=0.004), suggesting metabolic changes that occur with age may contribute to loss of coverage.

Conclusions : Our data suggest that both EC-specific Cav1 expression and leptin signaling support smooth muscle coverage and that loss of SMC coverage may result from metabolic alterations that occur with age. Future studies will assess the effect HFD (in young mice) on retinal SMC coverage. Additionally, we will investigate the potential involvement of Cav1 on age-dependent SMC retinal arteriole coverage.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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