Antiangiogenic effects and transcriptional regulation of pigment epithelium-derived factor in diabetic retinopathy

Wang, Binhui; Atherton, Philip J.; Patel, Rekha; Manning, Gillian; Donnelly, Richard

doi:10.1016/j.mvr.2010.02.012

Cited by 21 publications

(18 citation statements)

References 33 publications

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“…Although several authors found that patients with diabetes had depressed level of PEDF, controversy remains. 40 Increased levels of PEDF in diabetic rats were demonstrated by some authors in accordance with our results. 42 It may be argued that PEDF could be increased secondarily to protect the retina in response to diabetic impairment.…”

Section: Discussionsupporting

confidence: 93%

“…With chronic, ongoing damage, PEDF depletion may be a possibility. 8,9,40 In our study, rapamycin might have lowered PEDF levels through mTOR-dependent mechanisms. It has been claimed that PEDF secretion is negatively regulated by glucose, insulin (via mTOR-dependent pathway), and VEGF.…”

Section: Discussionmentioning

confidence: 48%

“…8,9,38 PEDF is a glycoprotein that was first identified from fetal human retinal pigment epithelial cell culture. 40,41 It is widely expressed throughout the body, especially in the nervous system and the retina. It has a very potent angiogenesis inhibiting action, in addition to prosurvival and antioxidant features.…”

Section: Discussionmentioning

confidence: 99%

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Rapamycin inhibits oxidative and angiogenic mediators in diabetic retinopathy

Özdemir

Kılınç

Ergün

et al. 2014

Canadian Journal of Ophthalmology

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 48%

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Rapamycin inhibits oxidative and angiogenic mediators in diabetic retinopathy

Özdemir

Kılınç

Ergün

et al. 2014

Canadian Journal of Ophthalmology

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“…We detected higher levels of PEDF in the diabetic group as compared with the control animals. Although several authors found that hyperglycemia depressed the level of PEDF in cell cultures, 30 controversy still exists. Elevated levels of PEDF in diabetic rats were demonstrated by some authors in accordance with our results.…”

Section: Pg/mg-protmentioning

confidence: 99%

Melatonin prevents retinal oxidative stress and vascular changes in diabetic rats

Özdemir

Ergün

Bakarış

et al. 2014

Eye

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Purpose To evaluate the role of melatonin, an antioxidant agent, in diabetic oxidative stress and vascular damage. Methods Diabetes was induced in 21 male Wistar rats by intraperitoneal (IP) administration of streptozotocin and then the rats were equally and randomly allocated to diabetic, melatonin, and vehicle groups. Seven healthy normal rats with similar features comprised the control group as the fourth group. All animals were followed for 12 weeks. The melatonin group received IP melatonin daily and the vehicle group received 2.5% ethanol IP at the last month. At the end of 12 weeks, the rats were killed and retinas were harvested. The retinas were investigated for the existence of hypoxiainducible factor 1-a (HIF-1a), vascular endothelial growth factor A (VEGF-A), and pigment epithelium-derived factor (PEDF) by ELISA. Retinal oxidative stress is quantitated by measuring nitrotyrosine and malondialdehyde levels. Retinal immunohistochemistry with antibody against CD31 antigen was carried out on retinal cross-sections. For statistics, ANOVA test was used for multiple comparisons. Results Hyperglycemia increased retinal oxidation as measured through levels of nitrotyrosine and malondialdehyde. Diabetic retinas are also associated with abnormal vascular changes such as dilatation and deformation. HIF-1a, VEGF-A, and PEDF were all increased because of diabetic injury. Melatonin showed a potential beneficial effect on retinopathy in diabetic rats. It decreased retinal nitrotyrosine and malondialdehyde levels, showing an antioxidative support. The vasculomodulator cytokines are decreased accordingly by melatonin therapy. Melatonin normalized retinal vascular changes as well. ConclusionMelatonin may show some advantage on diabetic vascular changes through decreasing oxidative stress and vessel-related cytokines.

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“…VEGF is known to inhibit the expression of PEDF [31]. In the pigment epithelium, the constitutively released VEGF [26] might continuously depress the expression of PEDF, and trapping of VEGF by bevacizumab might disinhibit the transcription of PEDF, resulting in upregulation of PEDF.…”

Section: Discussionmentioning

confidence: 99%