July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Daily low dose L-DOPA treatment delays the onset of retinal function deficits and improves retinal vascular function in STZ-induced diabetic rats
Author Affiliations & Notes
  • Kyle Christopher Chesler
    Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
  • Cara Motz
    Center for Visual and Neurocognitive Rehabilitation, Veterans Affairs Medical Center , Atlanta, Georgia, United States
  • Rachael S Allen
    Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
    Center for Visual and Neurocognitive Rehabilitation, Veterans Affairs Medical Center , Atlanta, Georgia, United States
  • P. Michael Iuvone
    Department of Ophthalmology, Emory University, Atlanta, Georgia, United States
  • Machelle T Pardue
    Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States
    Center for Visual and Neurocognitive Rehabilitation, Veterans Affairs Medical Center , Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Kyle Chesler, None; Cara Motz, None; Rachael Allen, None; P. Michael Iuvone, None; Machelle Pardue, None
  • Footnotes
    Support  This work was supported by the National Institutes of Health (NIH Grants P30 EY006360 and R01 EY004864 to P.M.I.); the Department of Veterans Affairs (Rehabilitation R&D Service Merit Award (I01RX2615) and Research Career Scientist Award (C9257) to M.T.P.); Research to Prevent Blindness (Departmental Award)”
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3580. doi:
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      Kyle Christopher Chesler, Cara Motz, Rachael S Allen, P. Michael Iuvone, Machelle T Pardue; Daily low dose L-DOPA treatment delays the onset of retinal function deficits and improves retinal vascular function in STZ-induced diabetic rats. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3580.

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

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Abstract

Purpose : Previous studies on STZ-induced diabetic rats have demonstrated that deficiencies in retinal dopamine levels contribute to retinal and visual deficits. Daily L-DOPA treatment (10 mg/kg) ameliorated dopamine deficiencies in the retina and preserved retinal and visual function. Here, we investigate the effectiveness of low dose L-DOPA (5 mg/kg) treatment coupled with a peripheral decarboxylase inhibitor (carbidopa) to preserve retinal function and prevent retinal functional hyperemia defects in STZ-induced diabetic rats.

Methods : Hyperglycemia was induced in pigmented Long Evans rats with streptozotocin (STZ;100 mg/kg; blood glucose >250 mg/dl). Rats were randomly assigned into four groups: Ctrl+Veh (n=4), Ctrl+L-DOPA (n=4), DM+L-DOPA (n=6) and DM+Veh (n=7). L-DOPA animals were injected daily each morning with 5 mg/kg L-DOPA and 1.5 mg/kg carbidopa in a 1:10 DMSO-Saline vehicle. Dark and light-adapted electroretinograms were recorded at 4 and 8-weeks post-STZ. Green flickering light-induced (530 nm; 12 Hz) vasodilation was measured through scanning laser ophthalmoscopy to assess retinal functional hyperemia (FH). Ctrl+L-DOPA and Ctrl+Veh groups were found to be statistically indistinguishable from one another, and therefore combined.

Results : DM+Veh rats showed significantly delayed OP implicit times from dim (p=0.019) and bright flash responses (p=0.011) compared to DM+L-DOPA animals at 4 weeks. DM+L-DOPA rats had significantly greater flicker induced arteriole vasodilation than both DM+Veh and control animals (p=0.031 and p=0.004, respectively) at 8 weeks. There were no significant differences in flicker induced vasodilatation in DM+Veh versus Ctrl rats.

Conclusions : Daily low dose L-DOPA with carbidopa treatment delayed the onset of retinal deficits for both rod- and cone-mediated responses. DM+L-DOPA treated animals showed greater flicker induced arteriole vasodilation than Ctrl and DM+Veh animals, suggesting that L-DOPA may directly alter retinal vasculature function. Overall, these results suggest that treatment with low dose L-DOPA coupled with carbidopa may provide benefit to retinal neuronal and vascular function during the early stages of diabetic retinopathy.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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