Targeting Neurovascular Interaction in Retinal Disorders

Fu, Zhongjie; Sun, Ye; Cakir, Bertan; Tomita, Yohei; Huang, Shuo; Wang, Zhongxiao; Liu, Chi-Hsiu; Cho, Steve S.; Britton, William; Kern, Timothy S.; Antonetti, David A.; Hellström, Ann

doi:10.3390/ijms21041503

Cited by 29 publications

(23 citation statements)

References 247 publications

(288 reference statements)

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“…The retina is the most energy-demanding tissue in the human body. A complex and organized retinal vascular network plays the critical role in delivering metabolites, which include oxygen, glucose, and lipid, to the eye [ 37 ]. Recently, a specific oxygen-binding protein is identified and named neuroglobin [ 38 , 39 ].…”

Section: Pathogenesis Of Ropmentioning

confidence: 99%

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Potential Effects of Nutraceuticals in Retinopathy of Prematurity

Tsang

Wolf

Pompoes

et al. 2021

Life

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Retinopathy of prematurity (ROP), the most common cause of childhood blindness, is a hypoxia-induced eye disease characterized by retinal neovascularization. In the normal retina, a well-organized vascular network provides oxygen and nutrients as energy sources to maintain a normal visual function; however, it is disrupted when pathological angiogenesis is induced in ROP patients. Under hypoxia, inadequate oxygen and energy supply lead to oxidative stress and stimulate neovasculature formation as well as affecting the function of photoreceptors. In order to meet the metabolic needs in the developing retina, protection against abnormal vascular formation is one way to manage ROP. Although current treatments provide beneficial effects in reducing the severity of ROP, these invasive therapies may also induce life-long consequences such as systemic structural and functional complications as well as neurodevelopment disruption in the developing infants. Nutritional supplements for the newborns are a novel concept for restoring energy supply by protecting the retinal vasculature and may lead to better ROP management. Nutraceuticals are provided in a non-invasive manner without the developmental side effects associated with current treatments. These nutraceuticals have been investigated through various in vitro and in vivo methods and are indicated to protect retinal vasculature. Here, we reviewed and discussed how the use of these nutraceuticals may be beneficial in ROP prevention and management.

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Section: Pathogenesis Of Ropmentioning

confidence: 99%

“…It can be converted to pyruvate as an energy source for oxidative phosphorylation. Lipid is another mitochondrial fuel for photoreceptors via fatty acid β-oxidation [ 37 ]. This process takes place in the mitochondria and peroxisome in mammals.…”

Section: Pathogenesis Of Ropmentioning

confidence: 99%

Potential Effects of Nutraceuticals in Retinopathy of Prematurity

Tsang

Wolf

Pompoes

et al. 2021

Life

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“…Gene deletion studies revealed Sema 4D contributes to diabetes induced vascular permeability and targeted antibodies against Sema 4D were additive with anti-VEGF antibodies in effectively reducing diabetes induced vascular permeability in animal models (Wu et al, 2020). Semaphorins act in guidance of the developing nervous system and these studies reveal a role in vascular function in the retina and a potential role in diabetic retinopathy (Fu et al, 2020).…”

Section: Introductionmentioning

confidence: 97%

The neuroscience of diabetic retinopathy

Antonetti

2021

Vis Neurosci

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Diabetic retinopathy remains a leading cause of blindness despite recent advance in therapies. Traditionally, this complication of diabetes was viewed predominantly as a microvascular disease but research has pointed to alterations in ganglion cells, glia, microglia, and photoreceptors as well, often occurring without obvious vascular damage. In neural tissue, the microvasculature and neural tissue form an intimate relationship with the neural tissue providing signaling cues for the vessels to form a distinct barrier that helps to maintain the proper neuronal environment for synaptic signaling. This relationship has been termed the neurovascular unit (NVU). Research is now focused on understanding the cellular and molecular basis of the neurovascular unit and how diabetes alters the normal cellular communications and disrupts the cellular environment contributing to loss of vision in diabetes.

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“…One such feature is the blood-retinal barrier (BRB), an analog of the blood-brain barrier (BBB) in the brain, which prevents the free access of blood, especially large molecular weight blood substances, to the delicate neural tissue. As part of the central nervous system (CNS), the retina forms a neurovascular unit (NVU) through the interaction of neurons, vascular cells, and glial cells (astrocytes and Müller) [ 1 ]. A retinal NVU is an anatomical structure to retain environmental homeostasis and a function unit to keep retinal cell function.…”

Section: Introductionmentioning

confidence: 99%

Pericyte-Endothelial Interactions in the Retinal Microvasculature

2020

IJMS

131

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Retinal microvasculature is crucial for the visual function of the neural retina. Pericytes and endothelial cells (ECs) are the two main cellular constituents in the retinal microvessels. Formation, maturation, and stabilization of the micro-vasculatures require pericyte-endothelial interactions, which are perturbed in many retinal vascular disorders, such as retinopathy of prematurity, retinal vein occlusion, and diabetic retinopathy. Understanding the cellular and molecular mechanisms of pericyte-endothelial interaction and perturbation can facilitate the design of therapeutic intervention for the prevention and treatment of retinal vascular disorders. Pericyte-endothelial interactions are indispensable for the integrity and functionality of retinal neurovascular unit (NVU), including vascular cells, retinal neurons, and glial cells. The essential autocrine and paracrine signaling pathways, such as Vascular endothelial growth factor (VEGF), Platelet-derived growth factor subunit B (PDGFB), Notch, Angipointein, Norrin, and Transforming growth factor-beta (TGF-β), have been well characterized for the regulation of pericyte-endothelial interactions in the neo-vessel formation processes (vasculogenesis and angiogenesis) during embryonic development. They also play a vital role in stabilizing and remodeling mature vasculature under pathological conditions. Awry signals, aberrant metabolisms, and pathological conditions, such as oxidative stress and inflammation, can disrupt the communication between pericytes and endothelial cells, thereby resulting in the breakdown of the blood-retinal barrier (BRB) and other microangiopathies. The emerging evidence supports extracellular exosomes’ roles in the (mis)communications between the two cell types. This review summarizes the essential knowledge and updates about new advancements in pericyte-EC interaction and communication, emphasizing the retinal microvasculature.

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Targeting Neurovascular Interaction in Retinal Disorders

Cited by 29 publications

References 247 publications

Potential Effects of Nutraceuticals in Retinopathy of Prematurity

Potential Effects of Nutraceuticals in Retinopathy of Prematurity

The neuroscience of diabetic retinopathy

Pericyte-Endothelial Interactions in the Retinal Microvasculature

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