Photoreceptor glucose metabolism determines normal retinal vascular growth

Fu, Zhongjie; Löfqvist, Chatarina; Liegl, Raffael; Wang, Zhongxiao; Sun, Ye; Gong, Yan; Liu, Chi Hsiu; Meng, Steven; Burnim, Samuel; Arellano, Ivana; Chouinard, My T.; Duran, Rubi; Poblete, Alexander; Cho, Steve S.; Akula, James D.; Kinter, Michael; Ley, David; Pupp, Ingrid Hansen; Talukdar, Saswata; Hellström, Ann; Smith, Lois E H

doi:10.15252/emmm.201707966

Cited by 49 publications

(103 citation statements)

References 66 publications

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“…Low α-ketoglutarate levels (as well as low oxygen levels) stabilize HIF-1α protein and increase the production of VEGF-A, which in turn induces pathological vessel formation [34]. In the neonatal mouse model of hyperglycemia-associated retinopathy, decreased photoreceptor glucose metabolism causes a reduction in the photoreceptor platelet-derived growth factor beta expression, thereby delaying normal retinal vascular development [40]. Ketone bodies, mainly beta hydroxybutyrate and acetoacetate, are alternative energy sources in the fasting state [41].…”

Section: Energy Shortage Drives Retinal Neovascularizationmentioning

confidence: 99%

“…The depletion of AdipoR1, which is a major adiponectin receptor gene, causes a shortage of essential ω-3 very-long-chain polyunsaturated fatty acids in the retina and in turn photoreceptor degeneration in mice [186,187]. Modulating photoreceptor metabolism with adiponectin administration protects against retinal dysfunction and improves retinal vascular development in mice modeling early ROP [40]. The adiponectin pathway inhibits neovascularization in a number of animal models of proliferative retinopathy [183,[188][189][190] and endothelial cell tube formation in vitro [191].…”

Section: Hormonal Modulationmentioning

confidence: 99%

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Targeting Neurovascular Interaction in Retinal Disorders

Sun

Cakir

et al. 2020

IJMS

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The tightly structured neural retina has a unique vascular network comprised of three interconnected plexuses in the inner retina (and choroid for outer retina), which provide oxygen and nutrients to neurons to maintain normal function. Clinical and experimental evidence suggests that neuronal metabolic needs control both normal retinal vascular development and pathological aberrant vascular growth. Particularly, photoreceptors, with the highest density of mitochondria in the body, regulate retinal vascular development by modulating angiogenic and inflammatory factors. Photoreceptor metabolic dysfunction, oxidative stress, and inflammation may cause adaptive but ultimately pathological retinal vascular responses, leading to blindness. Here we focus on the factors involved in neurovascular interactions, which are potential therapeutic targets to decrease energy demand and/or to increase energy production for neovascular retinal disorders.

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Section: Energy Shortage Drives Retinal Neovascularizationmentioning

confidence: 99%

Section: Hormonal Modulationmentioning

confidence: 99%

Targeting Neurovascular Interaction in Retinal Disorders

Sun

Cakir

et al. 2020

IJMS

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“…Dietary modulation of the lipid supply can positively influence diseases with pathological neovascularization such as ROP, AMD, and DR in patients and in animal models of retinopathy (Gong et al , ). Photoreceptor energy demands drive vessel growth (Sapieha, ; Joyal et al , , ; Fu et al , ), while photoreceptor‐derived oxidative stress and inflammation lead to retinal vascular damage or regression (Kern & Berkowitz, ; Sun et al , ). Retinal disorders such as ROP, DR, AMD, RP, and Zellweger spectrum disorder (ZSSD) are associated with disturbances in photoreceptor activity, which may further affect the blood supply and induce pathological vascular remodeling during disease progression.…”

Section: Dyslipidemia In Neurovascular Retinopathiesmentioning

confidence: 99%

“…This observation is supported by rodent studies. In mice, hyperglycemia (a key risk factor for ROP) triggers photoreceptor metabolic alterations and delays retinal vascular development (Fu et al , ). In rats, early photoreceptor dysfunction also predicts subsequent neovascularization (Akula et al , ).…”

Section: Dyslipidemia In Neurovascular Retinopathiesmentioning

confidence: 99%

Dyslipidemia in retinal metabolic disorders

Chen

Cagnone

et al. 2019

EMBO Mol Med

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The light‐sensitive photoreceptors in the retina are extremely metabolically demanding and have the highest density of mitochondria of any cell in the body. Both physiological and pathological retinal vascular growth and regression are controlled by photoreceptor energy demands. It is critical to understand the energy demands of photoreceptors and fuel sources supplying them to understand neurovascular diseases. Retinas are very rich in lipids, which are continuously recycled as lipid‐rich photoreceptor outer segments are shed and reformed and dietary intake of lipids modulates retinal lipid composition. Lipids (as well as glucose) are fuel substrates for photoreceptor mitochondria. Dyslipidemia contributes to the development and progression of retinal dysfunction in many eye diseases. Here, we review photoreceptor energy demands with a focus on lipid metabolism in retinal neurovascular disorders.

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“…Az emberi szervezetben az anyagcsere-folyamatok a proximalis tubulusokban és a fotoreceptorokban zajlanak a leggyorsabban, a hyperglykaemia pedig ezeken a területeken gátolja a mitokondriális oxidatív folyamatokat [46,47]. Adatok vannak arra vonatkozóan, hogy a hyperglykaemia a vese strukturális fejlődését is befolyásolja [48].…”

Section: áBraunclassified

Az extrém alacsony születési súlyú koraszülöttek hyperglykaemiájának korai és késői szövődményei

et al. 2019

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Introduction: During recent decades, the perinatal mortality of extremely low-birth weight infants has decreased. An important task is to recognize complications of prematurity. Aim: We made an attempt to explore the relationship between complications of prematurity and neonatal hyperglycemia. Method: From 1 January 2014 to 31 December 2017, 188 infants with birth weight below 1000 g were admitted. For each infant, the frequencies of hyperglycemia (blood glucose >8.5 mmol/l), retinopathy of prematurity, intraventricular hemorrhage, and bronchopulmonary dysplasia were determined. Animal studies were performed in Sprague Dawley rats. Hyperglycemia was achieved by intraperitoneal injection of streptozotocin (100 mg/kg). On the 7th day of life, aorta sections were prepared and stained with hematoxylin eosin. Wall thickness was measured using QCapture Pro 7 image analysis software. Results: The mean ± SD gestational age and birth weight were 27.1 ± 2.2 weeks and 814.9 ± 151.9 g; 33 infants (17.5%) died. Hyperglycemia was confirmed in 62 cases (32.9%), and insulin treatment was given to 43 infants (22.8%). The gestational age and birth weight of the hyperglycemic infants were significantly lower (p<0.001), the incidence of severe retinopathy (p = 0.012) and the mortality of insulin-treated patients were higher (p = 0.02) than in normoglycemic infants. Among survivors (n = 155), we found by logistic regression analysis that hyperglycemia was a risk factor for severe retinopathy (p<0.001). In the rat model, neonatal hyperglycemia caused significant thickening of the aortic wall. Conclusion: Our studies indicate that hyperglycemia is common in extremely low birth-weight infants. Monitoring of these infants for retinopathy of prematurity, kidney dysfunction, and hypertension is recommended. Orv Hetil. 2019; 160(32): 1270–1278.

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Photoreceptor glucose metabolism determines normal retinal vascular growth

Cited by 49 publications

References 66 publications

Targeting Neurovascular Interaction in Retinal Disorders

Targeting Neurovascular Interaction in Retinal Disorders

Dyslipidemia in retinal metabolic disorders

Az extrém alacsony születési súlyú koraszülöttek hyperglykaemiájának korai és késői szövődményei

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