Outer Retinal Oxidative Stress Measured In Vivo Using QUEnch-assiSTed (QUEST) OCT

Invest Ophthalmol Vis Sci. 2019 Apr 1;60(5):1566-1570. doi: 10.1167/iovs.18-26164.

Abstract

Purpose: To test the hypothesis that oxidative stress in the outer retina (OR = distance from external limiting membrane to the retinal pigment epithelium-choroid boundary) can be detected by using antioxidants (AOs) to correct an impaired light-evoked response as measured by optical coherence tomography (OCT).

Methods: C57BL/6J mice were maintained in the dark for ∼20 hours and studied by OCT before and after 1 hour of light exposure. OR thickness in dark or light was measured, and the light-dark difference (i.e., the photoresponse) was calculated. Subgroups of mice were given either saline or d-cis-diltiazem (an inducer of transient and nondamaging OR oxidative stress) ± methylene blue (24 hours before examination) and α-lipoic acid (1 hour before examination); one group was kept only in the dark and given only AOs.

Results: In uninjected or saline-injected control mice, the OR showed a similar and reproducible light-induced expansion; dark-adapted mice given AOs did not increase dark-adapted OR thickness. The d-cis-diltiazem-treated mice had no photoresponse (P > 0.05). The d-cis-diltiazem-treated mice given AOs corrected (P < 0.05) the suppressed OR photoresponse, indicating the presence of oxidative stress.

Conclusions: QUEnch-assiSTed (QUEST) OCT reproduced results from previous gold standard assays, showing that oxidative stress impairs the OR photoresponse and that d-cis-diltiazem produces OR oxidative stress. We envision future applications of QUEST OCT in a range of oxidative stress-based retinopathies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants
  • Bruch Membrane / pathology*
  • Calcium Channel Blockers / pharmacology
  • Dark Adaptation
  • Diltiazem / pharmacology
  • Light / adverse effects
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress* / physiology
  • Photic Stimulation
  • Radiation Injuries, Experimental / diagnostic imaging*
  • Radiation Injuries, Experimental / physiopathology
  • Retina / drug effects
  • Retina / physiopathology
  • Retina / radiation effects*
  • Retinal Degeneration / diagnostic imaging*
  • Retinal Degeneration / physiopathology
  • Retinal Pigment Epithelium / pathology*
  • Tomography, Optical Coherence

Substances

  • Antioxidants
  • Calcium Channel Blockers
  • Diltiazem