The neurovascular unit in retinopathy and neurodegenerative diseases

by Dane Sevenster

The prevalence of diabetes mellitus is on the rise globally, with Africa having an estimated increase of cases from 19 million to 47 million by 2045. Africa also has one of the highest percentages of undiagnosed cases with estimates that 60% of people are unaware they are living with diabetes. These predictions show the possible rise in economic and social costs facing Africa and the world as diabetes further grows into an epidemic.  

The increase in diabetes will in turn lead to a rise in one of the most common cause of blindness, diabetic retinopathy, especially in the population who are unaware of their condition and allow the disease to progress. Diabetic Retinopathy (DR) is one of the most common complications of diabetes and requires further investigation of the components and mechanisms that lead to early progression of the disease.  One such area that has received more attention has led to a great change in the understanding of the disease.  

The shift was in the focus on retinopathy as a solely microvascular disease into a combined neurodegenerative and microvascular disease. The review article of mention discusses the role of microvascular abnormalities and neurodegeneration in the pathogenesis of diabetic retinopathy, dementia and possibly other neurodegenerative diseases. The term neurovascular unit (NVU) arises often, which refers to the functional coupling and interdependency of neurons, glia and the highly specialized vasculature in the central nervous system (CNS). This NVU occurs within the retina of the eye and brain, forming a core component of the blood brain barrier to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. These cells maintain an intimate connection and are often the first to respond to inflammatory effects such as cell damage or pathogen invasion, sending subsequent signals to nearby cells that could disrupt the fine balance between pro- and anti-inflammatory pathways.  

Evidence shows that neurodegeneration via this NVU and its inflammatory response is an early event in the pathogenesis of diabetic retinopathy and other neurodegenerative diseases that could be linked to the development of microvascular abnormalities. The review states that the study of the underlying mechanisms leading to early disruption of the NVU, and later neurodegeneration is essential for the development of new therapeutic strategies. The below figure summarizes the potential mechanisms linking retinal neurodegeneration and early microvascular impairment, highlighting that impaired cell signaling within the neurovascular unit as a critical stage of early pathogenesis.   

What reveals the greatest evidence of the implications of the neurovascular unit and its future study is the idea that brain neurodegeneration as seen in Alzheimer’s may simultaneously occur with retinal neurodegeneration. Seeing as how many pathways such as insulin signalling impairment, low-grade inflammation, the accumulation of advanced glycation end-products (AGEs) and an increase in oxidative stress are replicated within both Alzheimer’s disease and retinopathy. This calls for investigation into the interdependence of these NVU components within the brain and retina, the relative contribution of each component, as well as the specifics of phenotypic or morphological changes that occur in the different cell types of the NVU to better explain the early progression of diabetic retinopathy, neurovascular and neurodegenerative diseases and hopefully provide insight into better therapies.  

The scope of research into these diseases has changed and grown over the years and the insights that can be gained from the NVU are promising, especially in the field of development of vaso- and neuroprotection therapies. 

References

  • Simó, R., Stitt, A. W. and Gardner, T. W. (2018) Neurodegeneration in diabetic retinopathy: does it really matter?, Diabetologia, Diabetologia, 61(9), pp. 1902–1912, [online] Available from: https://dx.doi.org/10.1007/s00125-018-4692-1. 
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