Inhibition of retinal neovascularization by a PEDF-derived nonapeptide in newborn mice subjected to oxygen-induced ischemic retinopathy

Zaitoun, Ismail; Wang, Shoujian; Darjatmoko, Soesiawati R.; Suscha, Andrew; Song, Yanning; Sorenson, Christine M.; Shifrin, Victor; Albert, Daniel M.; Melgar-Asensio, Ignacio; Kandela, Irawati; Henkin, Jack

doi:10.1016/j.exer.2020.108030

Cited by 11 publications

(7 citation statements)

References 47 publications

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“…However, and in contrast to our study performed in rats, Sheibani et al [21] have found that bevacizumab, the anti-human VEGF drug, did not reduce the avascular area nor the neovascularization in their murine OIR model. Stemming from the aforementioned comparison, although mice and rats both belong to rodent, murine and rat VEGF depicts different response to bevacizumab which challenge the nding from Yu et al [44] in which they emphasized that bevacizumab has poor a nity to murine VEGF.…”

Section: Discussioncontrasting

confidence: 99%

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Reduction of pathological retinal neovascularization, vessel obliteration and artery tortuosity by PEDF protein-based therapeutic in an oxygen-induced ischemic retinopathy rat model

Zhao,

Tschulakow,

Karthikeyan

et al. 2024

Preprint

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Retinopathy of prematurity (ROP) is a worldwide severe disease which can lead to visual impairment or even blindness. It is characterized by obliteration of retinal vessels, presence of tortuous vessels and pathological neovascularization in the retina. The current treatments, cryotherapy, laser ablation or intravitreal injection of anti-VEGF produce limited effect and ineluctable complications. There is therefore still a high medical need for alternative, efficient and safer therapies. Pigment epithelium-derived factor (PEDF), a potent angiogenesis inhibitor, appears late in gestation and its lack may contribute to ROP. Using an ex vivo model of ischemia and an in vivo model of choroidal neovascularization, we recently discovered that PEDF protein inhibited pathological neovascularization by protecting the endothelial cells which subsequently enhanced the survival of neural retinal cells and photoreceptors respectively. Here we examined the effect of PEDF protein alone or in combination with anti-VEGF drugs and compared their efficacy after a single intravitreal injection in an oxygen-induced ischemic retinopathy (OIR) rat model. PEDF protein alone or in combination with anti-VEGFs significantly suppressed the pathological neovascularization and reduced vessel obliteration compared to anti-VEGF drugs alone demonstrating that the treatment inhibited pathological neovascularization but not physiological angiogenesis. Importantly, PEDF protein-based therapeutics significantly reduced the artery tortuosity indicating an improvement of the retinal vasculature’s quality. No functional or histological side-effects were found in rat eyes after intravitreal protein injection even at high dose. Thus, the use of PEDF protein alone or combined with anti-VEGF is beneficial, and is a promising therapeutic for ROP.

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Section: Discussioncontrasting

confidence: 99%

“…Pigment epithelium-derived factor (PEDF) is a promising candidate for the treatment of ROP because it appears late in gestation and it has been suggested that its absence may contribute to ROP upon transition from high-to-ambient oxygen environment or with intermittent hypoxia [21]. PEDF is naturally expressed in eye tissues [22].…”

Section: Introductionmentioning

confidence: 99%

Reduction of pathological retinal neovascularization, vessel obliteration and artery tortuosity by PEDF protein-based therapeutic in an oxygen-induced ischemic retinopathy rat model

Zhao,

Tschulakow,

Karthikeyan

et al. 2024

Preprint

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“…The function and mechanism of PEDF action in fundus diseases mediated through other receptors have not been fully studied. Recent studies, however, have shown that in animal models of retinal NV (an OIR model and a laser-induced CNV model), both the PEDF 34mer and PEDF polypeptide 336 (PEDF 336) exhibit high affinity for LR (176). In a CNV model, PEDF 34mer spot treatment significantly inhibited the formation of CNV through its interaction with LR.…”

Section: Therapeutic Roles Of Pedf and Its Receptors In Ocular Fundus...mentioning

confidence: 99%

“…In a CNV model, PEDF 34mer spot treatment significantly inhibited the formation of CNV through its interaction with LR. In the OIR model, PEDF 336 bound LR with high affinity and inhibited retinal NV (176). In choroidal and retinal endothelial cells, VEGF induced LR expression, which can be inhibited by PEDF 336 (177).…”

Section: Therapeutic Roles Of Pedf and Its Receptors In Ocular Fundus...mentioning

confidence: 99%

“…In the OIR model, PEDF 336 bound LR with high affinity and inhibited retinal NV ( 176 ). In choroidal and retinal endothelial cells, VEGF induced LR expression, which can be inhibited by PEDF 336 ( 177 ). In addition, although the roles and mechanisms of PEDF and PLXDC in the eye have rarely been reported, considering that PEDF-activated PLXDC1 protected rat RGCs and that the combination of PEDF and PLXDC2 induced apoptosis of endothelial cells ( 41 ), these two membrane receptors may be important to PEDF effects on fundus diseases.…”

Section: Therapeutic Roles Of Pedf and Its Receptors In Ocular Fundus...mentioning

confidence: 99%

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Receptors that bind to PEDF and their therapeutic roles in retinal diseases

Chen

et al. 2023

Front. Endocrinol.

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Retinal neovascular, neurodegenerative, and inflammatory diseases represented by diabetic retinopathy are the main types of blinding eye disorders that continually cause the increased burden worldwide. Pigment epithelium-derived factor (PEDF) is an endogenous factor with multiple effects including neurotrophic activity, anti-angiogenesis, anti-tumorigenesis, and anti-inflammatory activity. PEDF activity depends on the interaction with the proteins on the cell surface. At present, seven independent receptors, including adipose triglyceride lipase, laminin receptor, lipoprotein receptor-related protein, plexin domain-containing 1, plexin domain-containing 2, F1-ATP synthase, and vascular endothelial growth factor receptor 2, have been demonstrated and confirmed to be high affinity receptors for PEDF. Understanding the interactions between PEDF and PEDF receptors, their roles in normal cellular metabolism and the response the initiate in disease will be accommodating for elucidating the ways in which inflammation, angiogenesis, and neurodegeneration exacerbate disease pathology. In this review, we firstly introduce PEDF receptors comprehensively, focusing particularly on their expression pattern, ligands, related diseases, and signal transduction pathways, respectively. We also discuss the interactive ways of PEDF and receptors to expand the prospective understanding of PEDF receptors in the diagnosis and treatment of retinal diseases.

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Pigment Epithelium Derived Factor in Ocular Vascular Development, Neovascularization and Function

Sorenson,

Song,

Sheibani

2024

Reference Module in Neuroscience and Biobehavioral Psychology

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Inhibition of retinal neovascularization by a PEDF-derived nonapeptide in newborn mice subjected to oxygen-induced ischemic retinopathy

Cited by 11 publications

References 47 publications

Reduction of pathological retinal neovascularization, vessel obliteration and artery tortuosity by PEDF protein-based therapeutic in an oxygen-induced ischemic retinopathy rat model

Reduction of pathological retinal neovascularization, vessel obliteration and artery tortuosity by PEDF protein-based therapeutic in an oxygen-induced ischemic retinopathy rat model

Receptors that bind to PEDF and their therapeutic roles in retinal diseases

Pigment Epithelium Derived Factor in Ocular Vascular Development, Neovascularization and Function

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