Common pathophysiology affecting diabetic retinopathy and Parkinson’s disease

Tian, Tian; Li, Zhaoming; Hong, Lü

doi:10.1016/j.mehy.2015.06.016

Cited by 16 publications

(10 citation statements)

References 24 publications

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“…MetS is a cluster of abnormalities that contribute to an increased risk of cardiovascular disease, type 2 diabetes mellitus, kidney disease, and overall mortality . Although diabetes is known to cause nerve damage such as retinopathy and peripheral neuropathy, little is understood about the relationship between MetS and the development of PD …”

Section: Physical Inactivity: Parkinson's Disease and Metabolic Syndromementioning

confidence: 99%

“…22,23 Although diabetes is known to cause nerve damage such as retinopathy and peripheral neuropathy, little is understood about the relationship between MetS and the development of PD. 27,72 Most studies have evaluated the risk of PD from a single component of MetS, rather than the sum of its parts. For example, increased body mass index and adiposity are associated with the risk of PD in a dose-dependent fashion in some 62,64,65 but not all studies.…”

Section: Physical Inactivity: Parkinson's Disease and Metabolic Syndromementioning

confidence: 99%

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The best medicine? The influence of physical activity and inactivity on Parkinson's disease

2016

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The incidence of Parkinson's disease (PD) is expected to increase as our population ages and will likely strain the projected capacity of our health care system. Despite being the most common movement disorder, there have been few noninvasive therapeutic advances for people with PD since the first levodopa clinical trial in 1961. The study of PD pathogenesis, combined with an appreciation for the biochemical mechanisms by which physical activity and exercise may impact physiology, has resulted in emerging hypotheses for new modifiable risk factors for PD. Physical activity and exercise as a means of preventing PD, or maintaining the functionality of people with PD, are a promising area of investigation. Conversely, physical inactivity is implicated in many disease states, some of which are also correlated with the development of PD, such as metabolic syndrome. The primary relationship between these diseases is likely rooted in heightened inflammation and oxidative stress at the cellular level. Physical activity and exercise as a means of attenuating inflammation have led to increased interest in related potential therapeutic targets for PD. Ultimately, these findings may translate into low‐cost, universally available therapies for PD disease modification or prevention. © 2016 International Parkinson and Movement Disorder Society

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Section: Physical Inactivity: Parkinson's Disease and Metabolic Syndromementioning

confidence: 99%

Section: Physical Inactivity: Parkinson's Disease and Metabolic Syndromementioning

confidence: 99%

The best medicine? The influence of physical activity and inactivity on Parkinson's disease

2016

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“… 5 , 6 It has previously been considered a microvascular disease, but recent evidence identifies retinal neurodegeneration as an early pathogenic event. 7–9 …”

Section: Introductionmentioning

confidence: 99%

Diabetic retinopathy as a potential marker of Parkinson’s disease: a register-based cohort study

Larsen

Thykjær

Pedersen

et al. 2021

Brain Communications

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Neurodegeneration is an early event in the pathogenesis of diabetic retinopathy, and an association between diabetic retinopathy and Parkinson’s disease has been proposed. In this nationwide register-based cohort study, we investigated the prevalence and incidence of Parkinson’s disease among patients screened for diabetic retinopathy in a Danish population-based cohort. Cases (n = 173 568) above 50 years of age with diabetes included in the Danish Registry of Diabetic Retinopathy between 2013 and 2018 were matched 1:5 by gender and birth year with a control population without diabetes (n = 843 781). At index date, the prevalence of Parkinson’s disease was compared between cases and controls. To assess the longitudinal relationship between diabetic retinopathy and Parkinson’s disease, a multivariable Cox proportional hazard model was estimated. The prevalence of Parkinson’s disease was 0.28% and 0.44% among cases and controls, respectively. While diabetic retinopathy was not associated with present (adjusted odds ratio 0.93, 95% confidence interval 0.72–1.21) or incident Parkinson’s disease (adjusted hazard ratio 0.77, 95% confidence interval 0.56–1.05), cases with diabetes were in general less likely to have or to develop Parkinson’s disease compared to controls without diabetes (adjusted odds ratio 0.79, 95% confidence interval 0.71–0.87 and adjusted hazard ratio 0.88, 95% confidence interval 0.78–1.00). In a national cohort of more than 1 million persons, patients with diabetes were 21% and 12% were less likely to have prevalent and develop incident Parkinson’s disease, respectively, compared to an age- and gender-matched control population without diabetes. We found no indication for diabetic retinopathy as an independent risk factor for incident Parkinson’s disease.

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“…When the retina is exposed to increased light levels dopamine is released by dopaminergic amacrine cells into the retinal space (Mills et al 2007; Perez-Fernandez et al 2019), where it mediates its effects in a paracrine manner by binding to D1, D2, and D4 receptors located on the various retinal neuronal subtypes (Cohen et al 1992; Derouiche and Asan 1999; Farshi et al 2016; Klitten et al 2008; Li et al 2013; Veruki and Wassle 1996). There is growing evidence that suggests this dopaminergic signaling is affected in early diabetes (Kim et al 2018; Lahouaoui et al 2016; Tian et al 2015; Vancura et al 2016), and could contribute to the changes in light adaptation that we observed. However, it is currently unknown whether this disruption is attributable to changes in downstream targets of dopamine, diminished release of dopamine by dopaminergic amacrine cells, or both.…”

Section: Introductionmentioning

confidence: 52%

Impaired light adaptation of ON-sustained ganglion cells in early diabetes is attributable to diminished dopamine D4 receptor sensitivity

Flood¹,

Wellington²,

Eggers³

2020

Preprint

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It has been known for some time that normal retinal signaling is disrupted early on in diabetes, before the onset of the vascular pathologies associated with diabetic retinopathy. There is growing evidence that levels of retinal dopamine, a neuromodulator that mediates light adaptation, may also be reduced in early diabetes. Previously, we have shown that after six weeks of diabetes in a mouse model, light adaptation is impaired at the level of ON-sustained (ON-s) ganglion cells. The purpose of this study was to determine whether changes in dopamine receptor sensitivity contribute to this dysfunction. Here we used single cell retinal patch-clamp recordings from the mouse retina to determine how activating dopamine type D4 receptors (D4Rs) changes the light-evoked and spontaneous excitatory inputs to ON-s ganglion cells, in both control and diabetic animals. We also used in-situ fluorescent hybridization to assess whether D4R expression was impacted by diabetes. We found that D4R activation had a smaller impact on light-evoked excitatory inputs to ON-s ganglion cells in diabetic retinas compared to controls. This impaired D4R signaling is not attributable to a decline in D4R expression, as we found increased D4R mRNA density in the outer plexiform layer in diabetic retinas. This suggests that the cellular machinery of dopaminergic signaling is itself disrupted in early diabetes and may be amenable to chronic dopamine supplementation therapy.

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Common pathophysiology affecting diabetic retinopathy and Parkinson’s disease

Cited by 16 publications

References 24 publications

The best medicine? The influence of physical activity and inactivity on Parkinson's disease

The best medicine? The influence of physical activity and inactivity on Parkinson's disease

Diabetic retinopathy as a potential marker of Parkinson’s disease: a register-based cohort study

Impaired light adaptation of ON-sustained ganglion cells in early diabetes is attributable to diminished dopamine D4 receptor sensitivity

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