June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Caveolin-1 deficiency accelerates age-related loss of contractile smooth muscle cells on retinal arteries
Author Affiliations & Notes
  • Alaina Reagan
    Ophthalmology/Neuroscience, OU Health Science Center, Oklahoma City, Oklahoma, United States
    Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Sijalu Paudel
    Biology, Cameron University, Lawton, Oklahoma, United States
  • Michael H Elliott
    Ophthalmology/Neuroscience, OU Health Science Center, Oklahoma City, Oklahoma, United States
    Dean McGee Eye Institute, Oklahoma City, Oklahoma, United States
  • Footnotes
    Commercial Relationships   Alaina Reagan, None; Sijalu Paudel, None; Michael Elliott, None
  • Footnotes
    Support  NIH R01EY019494, NIH core grant EY021725, NIH training grant T32-EY023202 and an unrestricted grant from Research to Prevent Blindness, Inc.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 4055. doi:
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    • Get Citation

      Alaina Reagan, Sijalu Paudel, Michael H Elliott; Caveolin-1 deficiency accelerates age-related loss of contractile smooth muscle cells on retinal arteries. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4055.

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

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Abstract

Purpose : In vivo measurements of healthy aged human subjects have shown significant heterogeneity in retinal arterial diameter as a function of length but a cellular/molecular mechanism for these observations has not been identified. Caveolin-1 (Cav-1) regulates myogenic tone in part through inhibition of endothelial nitric oxide synthase and we have previously shown that Cav-1 deficiency affects retinal vessel caliber. In this study, we provide evidence that healthy aging in wildtype mice results in segmental loss of contractile smooth muscle cells (SMCs) and correlated arteriolar diameter changes and that this phenotype occurs at an earlier age in Cav-1 KO mice.

Methods : Retinal whole mounts were prepared from young (6-7 months old) and old (24-27 months old) C57Bl6/j and Cav-1 KO mice, immunostained for vascular markers: CD31 (endothelium); alpha smooth muscle actin (αSMA; vascular SMCs); Cav-1, endothelium and mural cells) and/or NG2 (mural cells) and imaged by confocal microscopy. Contractile SMC coverage was analyzed using ImageJ software. In vivo imaging was performed on young and old transgenic mice expressing GFP under the aSMA promotor using Micron IV funduscopy.

Results : αSMA expression/coverage is significantly reduced (p<0.01; one-way ANOVA) in retinal arterioles from aged mice and show generalized increases in arteriolar diameters. Aged wildtype mice had significantly increased segmental loss, or gaps, of αSMA immunoreactivity that was usually associated with focal increases in arteriolar diameter compared to regions with αSMA coverage (number of gaps/area; p<0.001; one-way ANOVA.) The same age-related phenotype was observed at a younger age in Cav-1 KO compared to age-matched wildtype mice. αSMA coverage (p<0.001) and number of gaps/area (p<0.05) were significantly decreased and increased in the Cav-1 KO, respectively.

Conclusions : These data suggest that reduced expression of SMC contractile proteins in retinal arterioles is part of the normal aging process. Segmental loss of SMCs and focal increases in vessel diameters are consistent with functional studies showing microirregularities in arterial contractile responsiveness in aged human subjects. Cav-1 may control SMC phenotype/survival in retinal vessels. Declines in Cav-1 expression with age could contribute to alterations in retinal blood flow associated with aging.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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