Retinal pigment epithelium-secretome: A diabetic retinopathy perspective

Murugeswari, Ponnalagu; Subramani, Murali; Jayadev, Chaitra; Shetty, Rohit; Das, Debashish

doi:10.1016/j.cyto.2017.02.013

Cited by 95 publications

(70 citation statements)

References 109 publications

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“…The retinal pigment epithelium (RPE) is known to secrete a large range of neurotrophic factors important in the survival of neurons . In this study, we assessed the effects of high glucose and hypoxia, both of which are critical for the development of DR, on key factors that may be secreted by the RPE.…”

Section: Introductionmentioning

confidence: 99%

“…9 The retinal pigment epithelium (RPE) is known to secrete a large range of neurotrophic factors important in the survival of neurons. 10 In this study, we assessed the effects of high glucose and hypoxia, both of which are critical for the development of DR, on key factors that may be secreted by the RPE. Brain-derived neurotrophic factor (BDNF) and pigment epithelium-derived factor (PEDF) were selected due to their impact on RGC and photoreceptor survival.…”

Section: Introductionmentioning

confidence: 99%

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Effects of VEGF inhibitors on human retinal pigment epithelium under high glucose and hypoxia

Bahrami

Shen

Zhu

et al. 2019

Clinical Exper Ophthalmology

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Background Retinal pigment epithelium (RPE) is known to secrete factors important for retinal homeostasis. How this secretome changes in diabetic eyes treated with anti‐vascular endothelial growth factor (VEGF) inhibitors is unclear. Methods Diabetic conditions were simulated in vitro using ARPE‐19 cell‐line culture, with high glucose (25 mM) culture media, and hypoxia was chemically induced using cobalt chloride. Stress was assessed using cell viability assays as well as Western blots and enzyme‐linked immunosorbent assay (ELISA) for production of HIF‐1a and VEGF‐A. Production of neurotrophic factors was quantified once conditions were established using ELISA under stress with and without the addition of VEGF inhibitors. Changes were analysed with one‐way ANOVA. Results Hypoxia downregulated pigment epithelium‐derived factor (PEDF) expression. The addition of bevacizumab, ranibizumab and aflibercept in normoxic conditions all led to a significant downregulation of PEDF. Glucose concentration had no effect on secretion of PEDF. Brain‐derived neurotrophic factor (BDNF) secretion was downregulated in high glucose and was upregulated in hypoxia. Placental growth factor (PlGF) secretion by ARPE‐19 was undetectable by ELISA. Conclusions We found that hypoxia, high glucose or VEGF inhibitors affected secretion of neurotrophic factors. This variation under different conditions may influence neuron and photoreceptor survival in the diabetic state and VEGF inhibitor treated eyes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of VEGF inhibitors on human retinal pigment epithelium under high glucose and hypoxia

Bahrami

Shen

Zhu

et al. 2019

Clinical Exper Ophthalmology

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“…Excess of glucose interferes with plasma tumour necrosis alpha (TNFα) and interleukin 6 (IL6) and VEGF plasma levels, and reduced retinal oxygen levels stimulate the release of macrophages, chemokines and microglial growth factors, as well as the expression of angiogenic factors [87][88][89][90]. In DR, RPE cells also release inflammatory cytokines, chemokines and angiogenic factors (e.g., IL6, IL8, MCP-1, TGFβ and VEGF), which are mainly responsible for the development of the disease [91]. Monocyte chemoattractant protein-1 (MCP-1) influences retinal leukocyte infiltration as well as VEGF manifestation [92,93].…”

Section: Diabetic Retinopathy Angiogenesis and Anti-angiogenic Therapymentioning

confidence: 99%

Diabetic Retinopathy and Ocular Melanoma: How Far We Are?

et al. 2020

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Diabetic retinopathy causes vascular damage to retinal neurons, presenting characteristics of chronic inflammation. The development of new therapies capable of combating vision loss involves knowledge of inflammatory retinal changes. Studies in animal models and patients with diabetes have shown a high expression of the inflammatory molecules that are involved in the progression of diabetic retinopathy. Uveal melanoma is an eye tumour that remains highly deadly, because despite the correct treatment, it still causes metastasis in about 50% of patients. This type of tumour has the ability to produce and store melanin, which may result in resistance to therapy. Over time there has been development of new therapies for this disease, such as radiotherapy and surgical resection. In this review, we discuss diabetic retinopathy and ocular melanoma, their relationship with angiogenesis and the current anti-angiogenic therapies for their treatment.

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“…Among them, retinal pigment epithelium of the outer blood‐retinal barrier is one of the most vulnerable cellular components. The apoptosis of the retinal pigment epithelial cells, often induced by events such as imbalance in growth factor recreation, breakdown of active transport and metabolic processing, elevated productions of caspase proteins and reactive oxygen species, contributes to major pathological conditions in patients with diabetic retinopathy . However, although retinal pigment epithelium (RPE) seems to be playing crucial role in diabetic retinopathy, the underlying genetic network and molecular mechanisms of RPE diabetic apoptosis or injury remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA IGF2AS regulates high‐glucose induced apoptosis in human retinal pigment epithelial cells

Luo

Chen

et al. 2019

IUBMB Life

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High‐glucose‐induced retinal tissue impairment is the major pathological phenotype of diabetic retinopathy. In an in vitro diabetic apoptosis cell model, we evaluated the function of long noncoding RNA, insulin growth factor 2 antisense (IGF2‐AS) in high‐glucose‐injured human retinal pigment epithelial cells. A human retinal pigment epithelial cell line, ARPE‐19 was incubated with high‐glucose in vitro to induce apoptosis. SiRNA‐mediated IGF2‐AS downregulation was conducted in ARPE‐19 cells to evaluate its effect on high‐glucose induced apoptosis, assessed by a TUNEL assay. qRT‐PCR and western blot assays were applied to examine the functional effect of IGF2‐AS on IGF2/AKT/Casp‐9 expressions in glucose‐injured ARPE‐19 cells. ART was further knocked down, specifically in IGF2‐AS‐downregualted ARPE‐19 cells, to investigate its functional involvement in IGF2‐AS‐inhibition‐mediated apoptotic protection in glucose‐injured ARPE‐19 cells. High‐glucose induced apoptosis in ARPE‐19 cells, and upregulated IGF‐2AS in a dose‐dependent manner. SiRNA‐mediated IGF2‐AS downregulation ameliorated apoptosis, upregulated IGF2/AKT and decreased Casp‐9, in high‐glucose‐treated ARPE‐19 cells. AKT knockdown was shown to dramatically reverse the preventive effect of IGF2‐AS‐downregulation on high‐glucose‐induced apoptosis in ARPE‐19 cells. Moreover, it was demonstrated that AKT knockdown directly upregulated Casp‐9 in IGF2‐AS‐downregulated and high‐glucose‐treated ARPE‐19 cells. We demonstrated that inhibiting IGF2‐AS, possibly also through activation of AKT signaling pathway, has a protective function in high‐glucose‐induced apoptosis in human retinal pigment epithelial cells in diabetic retinopathy.

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Retinal pigment epithelium-secretome: A diabetic retinopathy perspective

Cited by 95 publications

References 109 publications

Effects of VEGF inhibitors on human retinal pigment epithelium under high glucose and hypoxia

Effects of VEGF inhibitors on human retinal pigment epithelium under high glucose and hypoxia

Diabetic Retinopathy and Ocular Melanoma: How Far We Are?

Long noncoding RNA IGF2AS regulates high‐glucose induced apoptosis in human retinal pigment epithelial cells

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