July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Clinically relevant timing of L-DOPA treatment in diabetic rats slows the progression of retinopathy
Author Affiliations & Notes
  • Kyle Chesler
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, Georgia, United States
  • Cara Motz
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, Georgia, United States
  • Rachael S Allen
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, Georgia, United States
    Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • P. Michael Iuvone
    Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia, United States
    Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia, United States
  • Machelle T Pardue
    Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
    Center for Visual and Neurocognitive Rehabilitation, Atlanta VA Healthcare System, Decatur, Georgia, United States
  • Footnotes
    Commercial Relationships   Kyle Chesler, None; Cara Motz, None; Rachael Allen, None; P. Michael Iuvone, None; Machelle Pardue, None
  • Footnotes
    Support  Dept of Veterans Affairs Rehab R&D Merit Award (RX002615) and VA Research Career Scientist Award (RX003134)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5972. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Kyle Chesler, Cara Motz, Rachael S Allen, P. Michael Iuvone, Machelle T Pardue; Clinically relevant timing of L-DOPA treatment in diabetic rats slows the progression of retinopathy. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5972.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Previous studies have demonstrated that daily L-DOPA treatment preserves retinal and visual function in diabetic (DM) rats. These studies started L-DOPA treatments at the onset of diabetes and therefore offer limited clinical translatability - it is more likely that drugs for diabetic retinopathy (DR) would be prescribed when retinal and visual deficits are detectable. Here, we investigate the efficacy of L-DOPA treatment to preserve visual, retinal, and vascular function in diabetic rats when treatment was started after the appearance of visual and retinal defects.

Methods : Hyperglycemia was induced in male pigmented Long Evans rats with streptozotocin (STZ;100 mg/kg; blood glucose >250 mg/dl). At 3 weeks post-STZ, rats showed retinal and visual deficits and began daily treatments. Rats were randomly assigned into four groups: Ctrl+Veh, Ctrl+L-DOPA, DM+L-DOPA and DM+Veh. L-DOPA treated rats were injected each morning with 10 mg/kg L-DOPA and 2.5 mg/kg carbidopa in a 1:10 DMSO-Saline vehicle. Spatial frequency thresholds using optomotor response and retinal function using dark and light-adapted electroretinograms were measured at pre-STZ baseline, 3, 6, and 10 weeks post-STZ. Retinal functional hyperemia was assessed using green flickering light (530 nm; 12 Hz) induced vasodilation at 6 and 10-weeks post-STZ.

Results : DM+L-DOPA rats showed preserved spatial frequency thresholds compared to DM+Veh rats after the onset of treatment. OP1 implicit times were delayed in DM+Veh rats and became progressively more delayed at 6 and 10-weeks post-STZ. DM+L-DOPA rats showed delayed OP1 implicit times at 3 weeks at the onset of treatment that worsened at 6-weeks, but trended towards recovery by 10-weeks. While there were no differences in flicker-induced vasodilation between DM+Veh versus Ctrl rats, DM+L-DOPA rats showed greater flicker induced arteriole vasodilation than all other groups at 6 and 10 weeks post-STZ.

Conclusions : L-DOPA treatments started at the first signs of dysfunction in STZ-induced diabetic rats protected from further spatial frequency declines, maintained retinal function, and enhanced neurovascular function. Taken together, these results complement previous findings that L-DOPA is protective against DR and suggest that starting L-DOPA treatment even after measurable vision loss may slow the progression of visual deficits.

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

 

×
×

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.

×