Dyslipidemia in retinal metabolic disorders

Fu, Zhongjie; Chen, Chuck T.; Cagnone, Gaël; Heckel, Émilie; Sun, Ye; Cakir, Bertan; Tomita, Yohei; Huang, Shuo; Li, Qian; Britton, William; Cho, Steve S.; Kern, Timothy S.; Hellström, Ann; Joyal, Jean‐Sébastien

doi:10.15252/emmm.201910473

Cited by 60 publications

(71 citation statements)

References 190 publications

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“…Thus early functional changes to the retina in diabetes include characteristic changes in the electroretinogram ( 103 ) as well as defects in autoregulation of vascular blood flow ( 104 ) which may be detectable before clinically visible signs of retinopathy appear. In addition, there are direct neurodegenerative changes to glial cells ( 105 , 106 ) and to photoreceptors ( 107 , 108 ). Recent reviews of diabetic retinopathy faithfully document the many pro-inflammatory changes which occur in the retina, involving nitric oxide (NO), cyclo-oxygenase ( 109 ), leukotrienes, vascular endothelial growth factor (VEGF) and more but do not highlight the fact that one of the central pro-inflammatory mediators is glucose at high concentration ( 110 ).…”

Section: Primary and Secondary Features Of Diabetic Retinopathymentioning

confidence: 99%

The Role of Inflammation in Diabetic Retinopathy

2020

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Inflammation is central to pathogenic processes in diabetes mellitus and the metabolic syndrome and particularly implicates innate immunity in the development of complications. Inflammation is a primary event in Type 1 diabetes where infectious (viral) and/or autoimmune processes initiate disease; in contrast, chronic inflammation is typical in Type 2 diabetes and is considered a sequel to increasing insulin resistance and disturbed glucose metabolism. Diabetic retinopathy (DR) is perceived as a vascular and neurodegenerative disease which occurs after some years of poorly controlled diabetes. However, many of the clinical features of DR are late events and reflect the nature of the retinal architecture and its cellular composition. Retinal microvascular disease is, in fact, an early event pathogenetically, induced by low grade, persistent leukocyte activation which causes repeated episodes of capillary occlusion and, progressive, attritional retinal ischemia. The later, overt clinical signs of DR are a consequence of the retinal ischemia. Metabolic dysregulation involving both lipid and glucose metabolism may lead to leukocyte activation. On a molecular level, we have shown that macrophage-restricted protein tyrosine phosphatase 1B (PTP1B) is a key regulator of inflammation in the metabolic syndrome involving insulin resistance and it is possible that PTP1B dysregulation may underlie retinal microvascular disease. We have also shown that adherent CCR5 + CD11b + monocyte macrophages appear to be selectively involved in retinal microvascular occlusion. In this review, we discuss the relationship between early leukocyte activation and the later features of DR, common pathogenetic processes between diabetic microvascular disease and other vascular retinopathies, the mechanisms whereby leukocyte activation is induced in hyperglycemia and dyslipidemia, the signaling mechanisms involved in diabetic microvascular disease, and possible interventions which may prevent these retinopathies. We also address a possible role for adaptive immunity in DR. Although significant improvements in treatment of DR have been made with intravitreal anti-VEGF therapy, a sizeable proportion of patients, particularly with sight-threatening macular edema, fail to respond. Alternative therapies targeting inflammatory processes may offer an advantage.

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Section: Primary and Secondary Features Of Diabetic Retinopathymentioning

confidence: 99%

The Role of Inflammation in Diabetic Retinopathy

2020

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“…(A) Structure of eye, cornea, and retina. Retina structure was adapted from (Fu et al, 2019). (B) Schematic representation on the stepwise generation of organoids.…”

Section: Retina Modelsmentioning

confidence: 99%

Organoids and Microphysiological Systems: New Tools for Ophthalmic Drug Discovery

Bai

Wang

2020

Front. Pharmacol.

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Organoids are adept at preserving the inherent complexity of a given cellular environment and when integrated with engineered micro-physiological systems (MPS) present distinct advantages for simulating a precisely controlled geometrical, physical, and biochemical micro-environment. This then allows for real-time monitoring of cell-cell interactions. As a result, the two aforementioned technologies hold significant promise and potential in studying ocular physiology and diseases by replicating specific eye tissue microstructures in vitro. This miniaturized review begins with defining the science behind organoids/MPS and subsequently introducing methods for generating organoids and engineering MPS. Furthermore, we will discuss the current state of organoids and MPS models in retina, cornea surrogates, and other ocular tissue, in regards to physiological/disease conditions. Finally, future prospective on organoid/MPS will be covered here. Organoids and MPS technologies closely recapture the in vivo microenvironment and thusly will continue to provide new understandings in organ functions and novel approaches to drug development.

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“…All of the inhibitors have a similar function -they mainly inhibit the formation of new retinal blood vessels by inactivating VEGF (Avery et al, 2014;Fu et al, 2016). However, it is important to note that ablation surgery may cause damage to the retina, and anti-VEGF treatments may inhibit the growth of normal vessels and neurons (Fu et al, 2019). It is crucial to find new ways to treat retinal NV.…”

Section: Targeting Neuroinflammation In Neovascular Retinal Diseasesmentioning

confidence: 99%

Targeting Neuroinflammation in Neovascular Retinal Diseases

2020

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Retinal blood vessels provide the necessary energy, nutrients and oxygen in order to support visual function and remove harmful particles from blood, thus acting to protect neuronal cells. The homeostasis of the retinal vessels is important for the maintenance of retinal visual function. Neovascularization is the most common cause of blindness in patients with retinopathy. Previous studies have shown that inflammatory mediators are known key regulators in retinopathy, but their causal link has been elusive. Although inflammation is often thought to arise from inflammatory cells like macrophages, neutrophils, and resident microglia, retinal neurons have also been reported to contribute to inflammation, through inflammatory signals, which mediate blood vessel growth. Therefore, it is important to explore the detailed mechanisms of neuroinflammation's effects on retinal neovascularization. This review looks to summarize current research on the relationship between retinal angiogenesis and neuroinflammation in retinopathy, as well as the potential effects of neuroinflammation on retinal neovascularization in different animal models.

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Dyslipidemia in retinal metabolic disorders

Cited by 60 publications

References 190 publications

The Role of Inflammation in Diabetic Retinopathy

The Role of Inflammation in Diabetic Retinopathy

Organoids and Microphysiological Systems: New Tools for Ophthalmic Drug Discovery

Targeting Neuroinflammation in Neovascular Retinal Diseases

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