Oxygen-induced retinopathy in mice with retinal photoreceptor cell degeneration

Zhang, Qian; Zhang, Zuoming

doi:10.1016/j.lfs.2014.02.023

Cited by 9 publications

(13 citation statements)

References 24 publications

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“…Vascular permeability in mice was assessed by the albumin extravasation assay method as described by others and us previously with slight modifications [ 24 , 47 – 49 ]. Briefly, at the end of the study, mice were anesthetized with isoflurane and received tail vein injection of FITC-BSA (100 mg/kg, Sigma-Aldrich).…”

Section: Methodsmentioning

confidence: 99%

Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2Akita mouse

et al. 2018

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BackgroundEarly-stage diabetic retinopathy (DR) is characterized by neurovascular defects. In this study, we hypothesized that human adipose-derived stem cells (ASCs) positive for the pericyte marker CD140b, or their secreted paracrine factors, therapeutically rescue early-stage DR features in an Ins2Akita mouse model.MethodsIns2Akita mice at 24 weeks of age received intravitreal injections of CD140b-positive ASCs (1000 cells/1 μL) or 20× conditioned media from cytokine-primed ASCs (ASC-CM, 1 μL). Age-matched wildtype mice that received saline served as controls. Visual function experiments and histological analyses were performed 3 weeks post intravitreal injection. Biochemical and molecular analyses assessed the ASC-CM composition and its biological effects.ResultsThree weeks post-injection, Ins2Akita mice that received ASCs had ameliorated decreased b-wave amplitudes and vascular leakage but failed to improve visual acuity, whereas Ins2Akita mice that received ASC-CM demonstrated amelioration of all aforementioned visual deficits. The ASC-CM group demonstrated partial amelioration of retinal GFAP immunoreactivity and DR-related gene expression but the ASC group did not. While Ins2Akita mice that received ASCs exhibited occasional (1 in 8) hemorrhagic retinas, mice that received ASC-CM had no adverse complications. In vitro, ASC-CM protected against TNFα-induced retinal endothelial permeability as measured by transendothelial electrical resistance. Biochemical and molecular analyses demonstrated several anti-inflammatory proteins including TSG-6 being highly expressed in cytokine-primed ASC-CM.ConclusionsASCs or their secreted factors mitigate retinal complications of diabetes in the Ins2Akita model. Further investigation is warranted to determine whether ASCs or their secreted factors are safe and effective therapeutic modalities long-term as current locally delivered therapies fail to effectively mitigate the progression of early-stage DR. Nonetheless, our study sheds new light on the therapeutic mechanisms of adult stem cells, with implications for assessing relative risks/benefits of experimental regenerative therapies for vision loss.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1059-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2Akita mouse

et al. 2018

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“…The rd10 mouse model is characterized by a hyperoxic environment due to the low oxygen consumption by the outer retina in which photoreceptors are mostly degenerated [ 28 , 29 ]. High oxygen tension almost halves the levels of the oxygen sensitive transcription factor HIF-1 [ 5 , 6 ] that we hypothesized to influence BAR2 levels in the retina.…”

Section: Resultsmentioning

confidence: 99%

Novel Insights into Beta 2 Adrenergic Receptor Function in the rd10 Model of Retinitis Pigmentosa

Cammalleri

Monte

Amato

et al. 2020

Cells

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Background: In retinitis pigmentosa (RP), inherited rod death is followed by cone loss and blindness. Why cones die is still a matter of consideration. Here, we investigate the pathogenic role of the sympathetic transmission in the rd10 mouse model of RP. Methods: Retinal levels of beta adrenergic receptor (BAR) 2 and norepinephrine (NE) were measured. After administration of the BAR1/2 blocker propranolol or the hypoxia-inducible factor (HIF)-1 activator dimethyloxalylglycine (DMOG), retinal levels of HIF-1α, BAR2 or proteins involved in BAR2 desensitization were also measured. In DMOG treated mice, expression and localization of BAR2, inflammatory markers and cone arrestin were determined. Finally, rd10 mice were subjected to electroretinogram (ERG) analysis to assess rod and cone function. Results: In the rd10 retina, BAR2 overexpression and NE accumulation were found, with BAR2 immunoreactivity localized to Müller cells. BAR2 overexpression was likely due to desensitization defects. Upregulated levels of BAR2 were drastically reduced by propranolol that also restored desensitization defects. Due to the low level of HIF-1 consequent to the hyperoxic environment in the rd10 retina, we hypothesized a link between HIF-1 and BAR2. HIF-1α stabilization with DMOG resulted in i. increased HIF-1α accumulation, ii. decreased BAR2 levels, iii. restored desensitization processes, iv. reduced expression of inflammatory markers and v. increased cone survival without improved retinal function. Conclusions: Our results support a pathogenic role of the sympathetic system in RP that might help to understand why rd10 mice show a positive response to BAR blockers.

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“…It has been postulated that oxygen demands of the photoreceptors cause the development of the vascular abnormalities that are characteristic of ROP [10,11]. In photoreceptor-degenerating mice exposed to oxygen in oxygen-induced retinopathy (OIR, modeling ROP), there are fewer preretinal vascular endothelial cell nuclei and reduced retinal VEGF expression level versus wild type (WT) OIR controls [12]. Therefore, understanding the roles of photoreceptor metabolic needs and factors involved in regulating retinal vascular responses is critical for disease prevention and treatment.…”

Section: Factors Influence Retinal Neurovascular Interactionmentioning

confidence: 99%

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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Oxygen-induced retinopathy in mice with retinal photoreceptor cell degeneration

Cited by 9 publications

References 24 publications

Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2Akita mouse

Adipose stem cells and their paracrine factors are therapeutic for early retinal complications of diabetes in the Ins2Akita mouse

Novel Insights into Beta 2 Adrenergic Receptor Function in the rd10 Model of Retinitis Pigmentosa

Targeting Neurovascular Interaction in Retinal Disorders

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