Vascular Endothelial Growth Factor Modulates the Function of the Retinal Pigment Epithelium In Vivo

Dahrouj, Mohammad; Alsarraf, Oday; McMillin, Jake C.; Liu, Yueying; Crosson, Craig E.; Ablonczy, Zsolt

doi:10.1167/iovs.13-13334

Cited by 21 publications

(31 citation statements)

References 37 publications

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“…Optical coherence tomography, which provides a crosssectional retinal image with high resolution, is used for not only clinical examination but also the experiments using animal models. 9,[18][19][20] However, it was difficult for us to detect a subtle change of retinal tissue after the venous occlusion (data not shown). In this study, therefore, we could not get more detailed findings using optical coherence tomography than histological examination and in situ hybridization.…”

Section: -6mentioning

confidence: 94%

Photocoagulation of the Retinal Nonperfusion Area Prevents the Expression of the Vascular Endothelial Growth Factor in an Animal Model

Gozawa

Takamura

Miyake

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. The purpose of this study was to evaluate whether photocoagulation of the retinal nonperfusion area suppresses ocular vascular endothelial growth factor (VEGF) expression in a rabbit retinal vein occlusion (RVO) model. METHODS.The retinas of pigmented rabbits were made ischemic by a laser on the main branch of retinal veins following intravenous injection of Rose Bengal. The eyes were enucleated before treatment and at 1, 7, and 14 days after laser occlusion. VEGF protein levels in the vitreous humor, sensory retina, and retinal pigment epithelium-choroid were measured with enzyme-linked immunosorbent assay. In situ hybridization of VEGF messenger RNA was performed to detect the location of VEGF expression in the sensory retina.RESULTS. In the vitreous body, the VEGF protein level in the RVO group, but not that in the RVO þ panretinal photocoagulation group, significantly increased on day 14. In the retina, the VEGF protein level in the RVO þ panretinal photocoagulation group was significantly higher than that in the RVO group on day 1, but was significantly lower than that in the RVO group on days 7 and 14. In the in situ hybridization analysis, the RVO group showed a high expression of VEGF in the inner nuclear and ganglion cell layers on days 7 and 14. In contrast, VEGF expression in the RVO þ panretinal photocoagulation group was strongly suppressed in both the inner nuclear and ganglion cell layers on days 7 and 14.CONCLUSIONS. This study is the first using an animal RVO model to demonstrate that laser photocoagulation of the retinal nonperfusion area suppresses VEGF-A expression in the retina.

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Section: -6mentioning

confidence: 94%

Photocoagulation of the Retinal Nonperfusion Area Prevents the Expression of the Vascular Endothelial Growth Factor in an Animal Model

Gozawa

Takamura

Miyake

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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“…Forty-eight hours after the intravitreal administration, one subretinal bleb per eye was generated using an injection of PBS following methods described previously (Dahrouj et al, 2014). In short, after setting the intraocular pressure at 10 mmHg via anterior segment cannulation, a 26-gauge needle was inserted 2-3 mm posterior to the limbus and a 33-gauge blunt needle was advanced through the larger needle across the vitreous under the guidance of a Spectralis OCT instrument (Heidelberg Engineering, Heidelberg, Germany).…”

Section: Methodsmentioning

confidence: 99%

“…Infrared fundus images and OCT tomograms (both in transverse and sagittal directions) as well as full volume scans were taken every ten minutes over the course of one hour using the Spectralis OCT instrument. Rates of bleb resorption were calculated using Graphpad Prism 6 software by linear regression analysis of the changes in bleb volume, as previously described (Dahrouj et al, 2014). All values represent mean ± SE.…”

Section: Methodsmentioning

confidence: 99%

“…To assess RPE fluid resorption and barrier function in vivo , we have recently developed a new methodology and have shown that VEGF induces a dramatic reduction in the rate of normal subretinal fluid resorption (Dahrouj et al, 2014). Although these optical coherence tomography (OCT) studies provided evidence of a potentially crucial role for VEGF in regulating RPE function in vivo , the experiments required the subretinal administration of higher than physiological amounts of VEGF.…”

Section: Introductionmentioning

confidence: 99%

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Receptor mediated disruption of retinal pigment epithelium function in acute glycated-albumin exposure

Dahrouj

Desjardins

Liu

et al. 2015

Experimental Eye Research

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Diabetic macular edema (DME) is a major cause of visual impairment. Although DME is generally believed to be a microvascular disease, dysfunction of the retinal pigment epithelium (RPE) can also contribute to its development. Advanced glycation end-products (AGE) are thought to be one of the key factors involved in the pathogenesis of diabetes in the eye, and we have previously demonstrated a rapid breakdown of RPE function following glycated-albumin (Glyc-alb, a common AGE mimetic) administration in monolayer cultures of fetal human RPE cells. Here we present new evidence that this response is attributed to apically oriented AGE receptors (RAGE). Moreover, time-lapse optical coherence tomography in Dutch-belted rabbits 48 hours post intravitreal Glyc-alb injections demonstrated a significant decrease in RPE-mediated fluid resorption in vivo. In both the animal and tissue culture models, the response to Glyc-alb was blocked by the relatively selective RAGE antagonist, FPS-ZM1 and was also inhibited by ZM323881, a relatively selective vascular endothelial growth factor receptor 2 (VEGF-R2) antagonist. Our data establish that the Glyc-alb-induced breakdown of RPE function is mediated via specific RAGE and VEGF-R2 signaling both in vitro and in vivo. These results are consistent with the notion that the RPE is a key player in the pathogenesis of DME.

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“…33,34 In some cases, VEGF may also induce the reduction of fluid absorption and be pathogenetic to edema. 35 This phenomenon suggests that VEGF plays a key role in regulating RPE barrier properties and leading to pathological retinal edema. 35 However, instead of VEGF and PlGF, we observed the involvement of PDGF-C in the hcy-facilitating activity for capillary angiogenesis in our model.…”

Section: Discussionmentioning

confidence: 99%

Homocysteine Facilitates Prominent Polygonal Angiogenetic Networks of a Choroidal Capillary Sprouting Model

Lee

Chiu

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Lee Y-J, Chiu C-C, Ke C-Y, Tien N, Lin P-K. Homocysteine facilitates prominent polygonal angiogenetic networks of a choroidal capillary sprouting model. Invest Ophthalmol Vis Sci. 2017;58:4332-4343. DOI: 10.1167/iovs.17-22308 PURPOSE. To investigate the effects of homocysteine on choroidal angiogenesis, we established an ex vivo choroidal sprouting explant model and examined the potential growth factors for angiogenesis.METHODS. Choroid fragments with retinal pigment epithelium were isolated from mouse and embedded in Matrigel. Homocysteine at different concentrations were added to the culture mediums. The choroidal explants were observed at different time points, and the total area of choroidal sprouting was measured and analyzed.RESULTS. Homocysteine evoked choroidal capillary sprouting by inducing capillary endothelial cell proliferation with pericyte formation and by facilitating polygonal angiogenetic networks. In some cases, vascular lumens were observed in the newly forming capillaries facilitated by homocysteine. The choroidal sprouting effect of homocysteine can only be observed at a certain range of homocysteine concentration, with 1-mM homocysteine exhibiting the most significantly increased choroidal sprouting areas. Isolectin overexpression was noted in the homocysteine-treated group. Possible growth factors for angiogenesis were detected through immunofluorescent staining, which demonstrated the overexpression of platelet-derived growth factor C and angiopoietin 1 in the homocysteine-treated preparations only. In these preparations, platelet-derived growth factor C was highly expressed in the tip cells of sprouting capillaries.CONCLUSIONS. We therefore conclude that platelet-derived growth factor C and angiopoietin 1 may play key roles in the choroid angiogenesis evoked by homocysteine.

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Vascular Endothelial Growth Factor Modulates the Function of the Retinal Pigment Epithelium In Vivo

Cited by 21 publications

References 37 publications

Photocoagulation of the Retinal Nonperfusion Area Prevents the Expression of the Vascular Endothelial Growth Factor in an Animal Model

Photocoagulation of the Retinal Nonperfusion Area Prevents the Expression of the Vascular Endothelial Growth Factor in an Animal Model

Receptor mediated disruption of retinal pigment epithelium function in acute glycated-albumin exposure

Homocysteine Facilitates Prominent Polygonal Angiogenetic Networks of a Choroidal Capillary Sprouting Model

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