# Dopamine treatments for diabetic retinopathy

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2020 · —

## Abstract

Diabetic retinopathy (DR) is already the leading cause of blindness in working age adults, and the
incidence of DR is predicted to double in the US by 2050 (NIH National Eye Institute data). With the prevalence
of diabetes in veterans significantly higher than the civilian population, it is imperative that we develop new and
more effective treatments for vision loss caused by DR. In the last funding cycle, we identified a novel
neuroprotective agent for early stage DR: dopamine. Our research confirmed a dopamine deficiency in retinas
of diabetic rodents and showed that treatment with the dopamine precursor, L-DOPA, protects against early
functional deficits in DR. The purpose of this proposal is to fill key knowledge gaps about dopamine treatment
for DR that are necessary to translate dopamine therapies to the clinic, including whether L-DOPA alters late
stage vascular deficits, the efficacy of long-term dopamine receptor agonist treatment, and the lowest
beneficial dose.
 Dopamine is an important neuromodulator in the retina that plays key roles in circadian rhythms, retinal
sensitivity under different lighting conditions, and visual function. In addition, loss of dopamine stimulates
angiogenesis. Thus, dopamine deficits caused by hyperglycemia may contribute to both neuronal and vascular
deficits in DR. Our preliminary results show that L-DOPA treatment in early stages of DR in rodents preserved
visual acuity and contrast sensitivity as measured by optokinetic tracking (OKT) and retinal function recorded
using electroretinography (ERG). However, the clinical impact of improving neuronal aspects of diabetic eye
disease is unknown. Most aspects of vision loss attributed to diabetes are related to vascular pathology
through either leakage and/or abnormal proliferation. Thus, it is critical to determine if dopaminergic treatment
also affects the vascular pathology through direct or indirect processes. In Aim 1, we will establish the role of
dopamine deficiency in neuronal and vascular pathology in DR by testing the hypothesis that L-DOPA
treatments will slow or halt early and late stage deficits in DR by protecting both retinal neurons and
vasculature.
 Dopamine diffuses through the retina by volume transmission and binds to dopamine receptors in
multiple cells types in the eye. Our preliminary data in diabetic mice show that acute treatment with dopamine
D1 and D4 receptor agonists can selectively restore visual acuity and contrast sensitivity, respectively. These
results suggest potential contributions of specific dopamine receptors to early visual dysfunction. In addition, a
D2 receptor agonist, bromocriptine, is already FDA approved for type 2 diabetes, but its role in DR has not
been directly studied. In Aim 2, we will elucidate the contribution of specific dopamine receptors on neuronal
and vascular dysfunction in DR by testing the hypothesis that dopamine receptors selectively modulate
neurons or vascular function such that dopamine receptor...

## Key facts

- **NIH application ID:** 9872906
- **Project number:** 5I01RX002615-03
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Machelle T. Pardue
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872906

## Citation

> US National Institutes of Health, RePORTER application 9872906, Dopamine treatments for diabetic retinopathy (5I01RX002615-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9872906. Licensed CC0.

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