Proliferative retinopathies: Angiogenesis that blinds

Sapieha, Przemysław; Hamel, David; Shao, Zhuo; Rivera, José Carlos; Zaniolo, Karine; Joyal, Jean Sébastien; Chemtob, Sylvain

doi:10.1016/j.biocel.2009.10.006

Cited by 119 publications

(114 citation statements)

References 60 publications

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“…All cells were terminally differentiated and prepared as described previously. 6 Approximately 10 6 cells were seeded before exposure to 2.0% O 2 levels. Supernatant was collected at the appropriate time points, centrifuged to remove debris, filtered with 0.2-m filters (Millipore), and distributed for proliferation assays (see "Cell proliferation assay").…”

Section: Preparation Of Conditioned Medium From Hypoxic Rgc-5mentioning

confidence: 99%

“…6 After blood vessel degeneration, neurons are metabolically starved and undergo several adaptive cellular changes to counter the ischemic state of the tissue. 3,6 If adequate vascular supply is not reinstated in time to salvage deprived neurons, it is conceivable that these severely hypoxic cells may mount a repulsive front in an attempt to shunt metabolic resources away from the perishing ischemic tissue toward less affected regions of the retina. In the process, excessive production of VEGF 7 induces exaggerated neovascularization at the periphery of the ischemic and repulsive zones into the pre-retinal region (normally devoid of vasculature), because reestablishing a vascular network to neurons that are unsalvageable would be wasteful.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 Throughout the vaso-obliterative phase of retinopathy, the local retinal environment is hostile to both vasculature and neurons. 6 After blood vessel degeneration, neurons are metabolically starved and undergo several adaptive cellular changes to counter the ischemic state of the tissue. 3,6 If adequate vascular supply is not reinstated in time to salvage deprived neurons, it is conceivable that these severely hypoxic cells may mount a repulsive front in an attempt to shunt metabolic resources away from the perishing ischemic tissue toward less affected regions of the retina.…”

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Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A

Joyal

Sitaras

Binet

et al. 2011

Blood

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The failure of blood vessels to revascularize ischemic neural tissue represents a significant challenge for vascular biology. Examples include proliferative retinopathies (PRs) such as retinopathy of prematurity and proliferative diabetic retinopathy, which are the leading causes of blindness in children and working-age adults. PRs are characterized by initial microvascular degeneration, followed by a compensatory albeit pathologic hypervascularization mounted by the hypoxic retina attempting to reinstate metabolic equilibrium. Paradoxically, this secondary revascularization fails to grow into the most ischemic regions of the retina. Instead, the new vessels are misdirected toward the vitreous, suggesting that vasorepulsive forces operate in the avascular hypoxic retina. In the present study, we demonstrate that the neuronal guidance cue semaphorin 3A (Sema3A) IntroductionProliferative retinopathies (PRs) are traditionally perceived as disorders limited to the microvasculature because of the characteristic profuse and deregulated growth of retinal vessels. 1 The mechanisms by which neovessels grow toward the vitreous and fail to revascularize ischemic zones are thought to result from high concentrations of proangiogenic factors such as VEGF in the vitreous of PR patients. However, if such an explanation were sufficient, retinal glial cells (astrocytes and Müller cells) 2 and neurons 3 that produce vast amounts of growth factors under hypoxic conditions should retain vessels on the retinal surface and ensure revascularization of the retina proper. It is, therefore, compelling to hypothesize the presence of a vasorepulsive force originating from the significantly hypoxic avascular retina that repels neovessels away from the vaso-obliterated retina and grows toward the vitreous.Neurovascular cross-talk shapes vascular development but has received limited attention in the pathology setting. In PRs, evidence points to an early decline in the function of ischemic regions of the neural retina, as shown by multifocal electroretinogram (mfERG). 4,5 Throughout the vaso-obliterative phase of retinopathy, the local retinal environment is hostile to both vasculature and neurons. 6 After blood vessel degeneration, neurons are metabolically starved and undergo several adaptive cellular changes to counter the ischemic state of the tissue. 3,6 If adequate vascular supply is not reinstated in time to salvage deprived neurons, it is conceivable that these severely hypoxic cells may mount a repulsive front in an attempt to shunt metabolic resources away from the perishing ischemic tissue toward less affected regions of the retina. In the process, excessive production of VEGF 7 induces exaggerated neovascularization at the periphery of the ischemic and repulsive zones into the pre-retinal region (normally devoid of vasculature), because reestablishing a vascular network to neurons that are unsalvageable would be wasteful.Given their established role in influencing endothelial cell (EC) behavior, classic neuronal guidance cues may ...

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Section: Preparation Of Conditioned Medium From Hypoxic Rgc-5mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A

Joyal

Sitaras

Binet

et al. 2011

Blood

Self Cite

163

199

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“…It is characterized by the development of sprouts from retinal vessels which in most cases penetrate the inner limiting membrane growing into the vitreous humor and leading to retinal detachment and blindness [14]. Retinal neovascularization is observed in ischemic retinopathies such as proliferative diabetic retinopathy, retinopathy of prematurity, central vein occlusion and branch retinal vein occlusion [15]. …”

Section: Ischemic Retinamentioning

confidence: 99%

The Neuropeptide Systems and their Potential Role in the Treatment of Mammalian Retinal Ischemia: A Developing Story

Cervia¹,

Casini²

2013

Current Neuropharmacology

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The multiplicity of peptidergic receptors and of the transduction pathways they activate offers the possibility of important advances in the development of specific drugs for clinical treatment of central nervous system disorders. Among them, retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Ischemia is a primary cause of neuronal death, and it can be considered as a sort of final common pathway in retinal diseases leading to irreversible morphological damage and vision loss. Neuropeptides and their receptors are widely expressed in mammalian retinas, where they exert multifaceted functions both during development and in the mature animal. In particular, in recent years somatostatin and pituitary adenylate cyclase activating peptide have been reported to be highly protective against retinal cell death caused by ischemia, while data on opioid peptides, angiotensin II, and other peptides have also been published. This review provides a rationale for harnessing the peptidergic receptors as a potential target against retinal neuronal damages which occur during ischemic retinopathies.

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“…In ROP, retinal neovascularization (RNV) plays a central role and may lead to blindness (1,3). The first phase of ROP is mainly characterized by delayed vascular growth, and the second phase is mainly present as RNV (4,5). The survival of lowbirth-weight infants is increasing due to the development of neonatal care.…”

Section: Introductionmentioning

confidence: 99%

Exogenous erythropoietin aggravates retinal neovascularizationin a murine model of proliferative retinopathy

Yang¹,

Zhang²,

He³

et al. 2017

Turk J Med Sci

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About 10-16 mouse pups were used per group, and both eyes were removed for experimental Background/aim: Erythropoietin (EPO) has been proven recently to be a critical mediator in retinal neovascularization (RNV). Previous studies have indicated that the use of recombinant human EPO (rEPO) is a high risk factor in the development of retinopathy of prematurity. In this study, we aimed to investigate the effect of rEPO administration on RNV and its underlying mechanism in a mouse model of oxygen-induced retinopathy (OIR). Materials and methods:A murine model of OIR was used to generate RNV. After daily intraperitoneal injection of rEPO from postnatal day 12 (P12), mice were euthanized at P17. Whole-mount retina staining was used to indicate the nonperfused area and neovascularization tufts. Preretinal neovascular cells were calculated through hematoxylin and eosin staining. The expression levels of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were detected via western blot analysis. Results:We found that injection of rEPO promoted the severity of RNV. The areas of neovascular tufts and preretinal neovascular cells were increased after administration of rEPO. When mice were injected with rEPO, a dose-dependent upregulation in VEGF and iNOS was observed. Conclusion:The study indicates the proangiogenic role of EPO, suggesting that rEPO contributes to the pathogenesis of RNV.

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Proliferative retinopathies: Angiogenesis that blinds

Cited by 119 publications

References 60 publications

Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A

Ischemic neurons prevent vascular regeneration of neural tissue by secreting semaphorin 3A

The Neuropeptide Systems and their Potential Role in the Treatment of Mammalian Retinal Ischemia: A Developing Story

Exogenous erythropoietin aggravates retinal neovascularizationin a murine model of proliferative retinopathy

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