Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

Bhutto, Imran Ahmed; McLeod, D. Scott; Hasegawa, Takuya; Kim, Sahng Y.; Merges, Carol; Tong, Peter C.Y.; Lutty, Gerard A.

doi:10.1016/j.exer.2005.05.007

Cited by 239 publications

(195 citation statements)

References 31 publications

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“…Further evidence that PEDF expression may reduce the likelihood of CNV is from immunohistochemistry of VEGF and PEDF in the RPE and choroid of eyes from AMD and control patients. Specifically, PEDF immunoreactivity was less in RPE/Bruch's membrane/choroid from patients who had had AMD than in age-matched controls (Bhutto et al, 2006). There is also evidence that some stresses, including hypoxia and oxidative stress, two factors associated with neovascular AMD and expression of VEGF, increase the VEGF/PEDF ratio tipping the balance of angiogenic stimulation/inhibition to favor the development of neurosensory retinal CNV.…”

Section: Vegf To Pedf Ratiomentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

614

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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Section: Vegf To Pedf Ratiomentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

614

527

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“…33,34 Recently, we reported a reduction of VEGF gene expression in the retina of OXYS rats compared to the parent Wistar strain (control) during retinopathy progression 12 ; this effect may be linked to the early alterations in RPE cells and choroid vessels in OXYS rats. We supposed that such changes are prerequisite to the development of retinopathy and that their reversal is necessary for the prevention of the disease.…”

Section: Discussionmentioning

confidence: 99%

The mitochondria-targeted antioxidant SkQ1 restoresαB-crystallin expression and protects against AMD-like retinopathy in OXYS rats

et al. 2014

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Abbreviations: AMD, age-related macular degeneration; RPE, retinal pigment epithelium; SkQ1, 10-(6 0 plastoquinonyl)decyltriphenylphosphonium.Age-related macular degeneration (AMD), a neurodegenerative and vascular retinal disease, is the leading cause of blindness in the developed world. Accumulating evidence suggests that alterations in the expression of a small heat shock protein (aB-crystallin) are involved in the pathogeneses of AMD. Here we demonstrate that senescenceaccelerated OXYS rats-an animal model of the dry form of AMD-develop spontaneous retinopathy against the background of reduced expression of aB-crystallin in the retina at the early preclinical stages of retinopathy (age 20 days) as well as at 4 and 24 months of age, during the progressive stage of the disease. The level of aA-crystallin expression in the retina of OXYS rats at all the ages examined was no different from that in disease-free Wistar rats. Treatment with the mitochondria-targeted antioxidant SkQ1 (plastoquinonyl-decyltriphenylphosphonium) from 1.5 to 4 months of age, 250 nmol/kg, increased the level of aB-crystallin expression in the retina of OXYS rats. SkQ1 slowed the development of retinopathy and reduced histological aberrations in retinal pigment epithelium cells. SkQ1 also attenuated neurodegenerative changes in the photoreceptors and facilitated circulation in choroid blood vessels in the retina of OXYS rats; this improvement was probably linked with the restoration of aB-crystallin expression.

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“…4 In tissues from AMD patients, PEDF is significantly lower in RPE cells, the Bruch's membrane, and the choroid than in control eyes. These data suggest that a decrease in PEDF may disrupt the balance of these 2 factors and create a proangiogenic environment that promotes choroidal neovascularization.…”

Section: Genetically Altered Mouse Models Of Angiogenesismentioning

confidence: 99%

“…The apical aspect of RPE cells is intimately associated with photoreceptor outer segments (Figs. [3][4][5]. Photoreceptor outer segments are continually renewed from their base, and a major function of RPE cells is to remove oxidized outer-segment disc material.…”

Section: The Retinal Pigment Epitheliummentioning

confidence: 99%

REVIEW PAPER: Animals as Models of Age-Related Macular Degeneration

Zeiss

2010

Vet Pathol

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Age-related macular degeneration (AMD) is a degenerative condition that begins in Bruch's membrane and progresses to involve the retinal pigment epithelium and ultimately the overlying photoreceptors. The only required etiologic factor is age, and AMD is regarded as the leading cause of blindness in individuals older than 65 years. AMD results from variable contributions of age, environment, and genetic predisposition. Many loci are linked to AMD; in the majority of cases, the disease is associated with polymorphisms within these genes, rather than mutations that ablate gene function. The etiologic complexity of AMD is reflected by the paucity of animal models that entirely replicate the human disease. This review compares the salient anatomy of the primate and rodent retina, particularly in the light of AMD pathology. It next discusses prevailing hypotheses explaining how AMD may develop. These include the role of complement activation and macrophage chemotaxis in AMD, molecular mechanisms of choroidal neovascularization, and the roles of oxidative damage and lipid metabolism. Finally, the article gives an overview of spontaneous and induced nonhuman primate models and describes relevant mouse models in the context of each pathogenetic mechanism. KeywordsBruch's membrane, choriocapillaris, complement, degeneration, macula, retinal pigment epithelium Age-related macular degeneration (AMD) is a progressive condition of the retinal pigment epithelium (RPE), its supporting basement membrane, and the overlying photoreceptor layer. It affects the macula, the central area of the retina responsible for high-acuity daylight vision. Among individuals older than 65 years, AMD is regarded as the leading cause of blindness in the industrialized world. 39AMD has no single cause and results from variable contributions of age, genetic predisposition, and environment. Established epidemiologic risk factors include cigarette smoking, diet, female sex, Caucasian race, and a family history of AMD.52,60,61 Because AMD is rare in individuals younger than 55 years, the only required risk factor is age, which implicates the multitude of cellular changes that accompany normal aging in the pathogenesis of AMD. The challenge is to identify how these are altered to tip the process toward overt disease.With age, most people accumulate small, well-demarcated deposits of extracellular material beneath the RPE. 5,45 These are known as small, hard drusen and are not pathogenic. However, if these deposits enlarge, they become associated with regional RPE loss and eventual degeneration of overlying photoreceptors. These changes are funduscopically visible, and their progression is used to classify lesions along the continuum of early to late dry AMD. 18 The pathogenetic mechanisms of this process center on inflammation, oxidative damage, and RPE senescence 45 and are predominantly modeled in the mouse.In the minority of cases, late AMD is accompanied by growth of blood vessels from the choroid through Bruch's membrane toward the retina. ...

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Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) in aged human choroid and eyes with age-related macular degeneration

Cited by 239 publications

References 31 publications

Vascular endothelial growth factor in eye disease

Vascular endothelial growth factor in eye disease

The mitochondria-targeted antioxidant SkQ1 restoresαB-crystallin expression and protects against AMD-like retinopathy in OXYS rats

REVIEW PAPER: Animals as Models of Age-Related Macular Degeneration

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