June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Metabolic impacts of cigarette smoke on the retina of complement-compromised mice
Author Affiliations & Notes
  • Felix R Vazquez-Chona
    Ophthalmology, Univ of Utah, Salt Lake City, Utah, United States
  • Alexandra Butler
    Ophthalmology, Univ of Utah, Salt Lake City, Utah, United States
  • Emilie McKinnon
    Medical University of South Carolina, Charleston, South Carolina, United States
  • Baerbel Rohrer
    Medical University of South Carolina, Charleston, South Carolina, United States
  • Bryan W Jones
    Ophthalmology, Univ of Utah, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Felix Vazquez-Chona, None; Alexandra Butler, None; Emilie McKinnon, None; Baerbel Rohrer, None; Bryan Jones, None
  • Footnotes
    Support  NIH EY02576, NIH EY015128, NIH EY014800 Vision Core, Research to Prevent Blindness, Thome Foundation Bank of America, NSF 0941717
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 2282. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Felix R Vazquez-Chona, Alexandra Butler, Emilie McKinnon, Baerbel Rohrer, Bryan W Jones; Metabolic impacts of cigarette smoke on the retina of complement-compromised mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2282.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : The interaction between metabolism and the immune system is hypothesized as playing a central role in the pathology of neural diseases including Age-Related Macular Degeneration (AMD). We investigated the effects of cigarette-smoke exposure (CSE) on metabolism of retinal cells in wild-type (wt) mice, and mice deficient for the alternative pathway (complement factor B, CfB) or common terminal pathway (complement component 3, C3).

Methods : Mice were exposed to CSE or room filtered-air (controls) for 6 h/d, 5 d/wk for 6 months. We visualized the metabolism of retinal cells using Computational Molecular Phenotyping (CMP). Retinal cell classification and metabolic adaptation were interrogated using arginine (R), aspartate (D), GABA (γ), glutamate (E), glycine (G), glutathione (J), glutamine (Q), taurine (τ), glutamine synthetase (GS), and cellular retinaldehyde binding protein (CRALBP). Electron microscope mosaics were instrumental in phenotyping metabolic profiles.

Results : CSE C3-/- animals show more severe degenerative indices than CSE WT: retinal pigment epithelium (RPE) exhibited a decreased basalateral infolding area and increased vacuolization; photoreceptors show increased mitochondrial swelling and pyknosis; Müller glia displayed hypertrophy; and the amacrine layer was affected by increased vacuolization. The CfB-/- retina was more resilient to the negative effects of CSE when compared to the WT retina. At the metabolic level, RPE and inner segments of CSE CfB-/- mice displayed modest changes. In contrast, changes in CSE C3-/- and WT retina were dramatic: RPE exhibited decreased CRALBP and elevated R-E-J-τ-γ levels; inner segments showed increased R-D-E-G-J-Q-τ-γ-CRALBP; and Müller glia were found to have decreased levels along the R-D-E-G-J-Q-τ-γ-GS-CRALBP axis.

Conclusions : Increased GABA levels in RPE and photoreceptors are consistent with Müller glia dysfunction. Our metabolic profiling suggests that RPE and Müller glia are vulnerable to CSE-induced oxidative stress. We also find that the potential complement activation status of the retina-RPE-choroid unit highly influences the metabolic response of retinal cells to CSE. As complete blockade of the complement system in the C3-/- model has a more dramatic impact on metabolism of RPE, Müller glia, and photoreceptors than observed in the CfB-/- model, it can be proposed that downstream signaling of the complement system is required for retina health.

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×