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Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Ophthalmology
  • diabetes
  • retina
  • dopamine
  • retinopathy
  • neuroprotection
  • VASCULAR-PERMEABILITY
  • PARKINSONS-DISEASE
  • VISUAL DYSFUNCTION
  • MODEL
  • LEVODOPA
  • DEFICITS
  • ELECTRORETINOGRAM
  • THERAPY
  • DELAYS
  • STRIATUM

Initiation of L-DOPA Treatment After Detection of Diabetes-Induced Retinal Dysfunction Reverses Retinopathy and Provides Neuroprotection in Rats

Tools:

Journal Title:

TRANSLATIONAL VISION SCIENCE & TECHNOLOGY

Volume:

Volume 10, Number 4

Publisher:

, Pages 8-8

Type of Work:

Article

Abstract:

Purpose: L-DOPA treatment initiated at the start of hyperglycemia preserves retinal and visual function in diabetic rats. Here, we investigated a more clinically relevant treatment strategy in which retinal and visual dysfunction designated the beginning of the therapeutic window for L-DOPA treatment. Methods: Spatial frequency thresholds using optomotor response and oscillatory potential (OP) delays using electroretinograms were compared at baseline, 3, 6, and 10 weeks after streptozotocin (STZ) between diabetic and control rats. L-DOPA/carbidopa treatment (DOPA) or vehicle was delivered orally 5 days per week beginning at 3 weeks after STZ, when significant retinal and visual deficits were measured. At 10 weeks after STZ, retinas were collected to measure L-DOPA, dopamine, and 3,4-dihydroxyphenylacetic acid (DOPAC) levels using high-performance liquid chromatography. Results: Spatial frequency thresholds decreased at 6 weeks in diabetic vehicle rats (28%), whereas diabetic DOPA rats had stable thresholds (<1%) that maintained to 10 weeks, creating significantly higher thresholds compared with diabetic vehicle rats (P < 0.0001). OP2 implicit times in response to dim, rod-driven stimuli were decreased in diabetic compared with control rats (3 weeks, P < 0.0001; 10 weeks, P < 0.01). With L-DOPA treatment, OP2 implicit times recovered in diabetic rats to be indistinguishable from control rats by 10 weeks after STZ. Rats treated with L-DOPA showed significantly increased retinal L-DOPA (P < 0.001) and dopamine levels (P < 0.05). Conclusions: L-DOPA treatment started after the detection of retinal and visual dysfunction showed protective effects in diabetic rats. Translational Relevance: Early retinal functional deficits induced by diabetes can be used to identify an earlier therapeutic window for L-DOPA treatment which protects from further vision loss and restores retinal function.
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