Varied expression of functionally important genes of RPE and choroid in the macula and in the periphery of normal human eyes

Kociok, Norbert; Joussen, Antonia M.

doi:10.1007/s00417-006-0266-x

Cited by 36 publications

(22 citation statements)

References 32 publications

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“…Clinically, in eyes from patients without AMD, PEDF mRNA was 10 fold greater than was VEGF mRNA and was also more significantly expressed in peripheral RPE than in macular RPE (Kociok and Joussen, 2007). These data support clinical observations that CNV occurs in the macula much more often than in the peripheral retina.…”

Section: Vegf To Pedf Ratiosupporting

confidence: 78%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

596

503

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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 Ratiosupporting

confidence: 78%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

596

503

View full text Add to dashboard Cite

show abstract

“…In the normal adult eye (especially in macular region), the concentration of PEDF is tenfold higher than VEGF, which may suggest that PEDF is the main factor responsible for the low number of blood vessels associated with macular avascularity (Kociok & Joussen 2007, Kozulin et al 2010. However, the level of PEDF in the vitreous of the eye in patients suffering from proliferative diseases such as PDR is significantly lower than in the normal eye, which may be a biomarker of oxidative stress in the eye, and the pharmacological upregulation or administration of PEDF may be a therapeutic strategy to address PDR (Yokoi et al 2007).…”

Section: Clinical Implications and Possible Future Studiesmentioning

confidence: 99%

Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy

Elahy¹,

Baindur-Hudson²,

Cruzat³

et al. 2014

Journal of Endocrinology

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Pigment epithelium-derived factor (PEDF) is a pluripotent glycoprotein belonging to the serpin family. PEDF can stimulate several physiological processes such as angiogenesis, cell proliferation, and survival. Oxidative stress plays an important role in the occurrence of diabetic retinopathy (DR), which is the major cause of blindness in young diabetic adults. PEDF plays a protective role in DR and there is accumulating evidence of the neuroprotective effect of PEDF. In this paper, we review the role of PEDF and the mechanisms involved in its antioxidative, anti-inflammatory, and neuroprotective properties.

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“…This close anatomical association between the RPE and photoreceptors is one of the factors that promotes the ability of the RPE to, on the one hand, provide nutrients and oxygen to the photoreceptor cells and, on the other hand, eliminate metabolic wastes generated by the neural retina, including those resulting from the shedding of outer segments tips and their subsequent phagocytosis and degradation by the RPE. The RPE cells express a variety of lipoprotein-specifi c and scavenger receptors: VLDL receptor ( 47 ), LDL receptor (LDL-R) ( 12,48,49 ), and the so-called scavenger receptors CD36 ( 48,(50)(51)(52)(53)(54), SR-BI, and BII ( 50,52,55,56 ). Interestingly, LDL-R was also localized to the endothelial cells of the choriocapillaris, the photoreceptor inner segments, retinal ganglion cells, and Müller cells ( 12 ).…”

Section: Uptake and Intraretinal Exchange Of Cholesterol By The Retinamentioning

confidence: 99%

The ins and outs of cholesterol in the vertebrate retina

Fliesler

Brétillon

2010

Journal of Lipid Research

125

122

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Journal of Lipid Research Volume 51, 2010 3399 plus glial cells (Müller cells, astrocytes, and microglia).[For an excellent overview of retinal structure and cytoarchitecture, see ( 1 ) and http://webvision.med.utah. edu/]. The neuronal cells are distributed into discrete histological layers in the fully differentiated retina ( Fig. 1 ), with the ganglion cell layer arranged proximal to the vitreous and the photoreceptor cells (rods and cones) residing at the opposite side of the neural retina, just underneath the retinal pigment epithelium (RPE) layer. The RPE is a monolayer of polarized epithelial cells that serves as the interface between the neural retina and the choroid, the blood supply to the outer cell layers of the retina. The apical tips of the photoreceptor outer segments (OS) are adjacent to and invaginate into the apical face of the RPE (one of the few examples of apical-apical cellular contact in the body) ( Fig. 1C ). Bruch's membrane (BrM; Fig. 1B, C ) is not a membrane, per se, but rather a pentalaminar structure that consists of the basement membranes of the RPE cells and the endothelial cells of the choriocapillaris ( Fig. 1C ), plus the extracellular matrix that fi lls the space between these two membranes [reviewed in ( 2, 3 )].The relatively modest compendium of cell types mentioned above, however, belies the amazing, higher order complexity of this sensory tissue. It has been estimated that there are actually about 55 anatomically distinct neuronal cell types in the adult mammalian retina, of which about 22 have been thoroughly characterized with regard to their fi ne structure and functional repertoire [reviewed in ( 4 )]. For example, photoreceptors consist of both rods and cones, with cones being subdivided into two (three in Abstract The vertebrate retina has multiple demands for utilization of cholesterol and must meet those demands either by synthesizing its own supply of cholesterol or by importing cholesterol from extraretinal sources, or both. Unlike the blood-brain barrier, the blood-retina barrier allows uptake of cholesterol from the circulation via a lipoprotein-based/receptor-mediated mechanism. Under normal conditions, cholesterol homeostasis is tightly regulated; also, cholesterol exists in the neural retina overwhelmingly in unesterifi ed form, and sterol intermediates are present in minimal to negligible quantities. However, under certain pathological conditions, either due to an inborn error in cholesterol biosynthesis or as a consequence of exposure to selective inhibitors of enzymes in the cholesterol pathway, the ratio of sterol intermediates to cholesterol in the retina can rise dramatically and persist, in some cases resulting in progressive degeneration that signifi cantly compromises the structure and function of the retina. The mature vertebrate retina is a highly stratifi ed, multicellular tissue classically described as consisting of six fundamental neuronal cell types (photoreceptor, bipolar, ganglion, horizontal, amacrine, and interplexiform cells) the normal...

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Varied expression of functionally important genes of RPE and choroid in the macula and in the periphery of normal human eyes

Cited by 36 publications

References 32 publications

Vascular endothelial growth factor in eye disease

Vascular endothelial growth factor in eye disease

Mechanisms of PEDF-mediated protection against reactive oxygen species damage in diabetic retinopathy and neuropathy

The ins and outs of cholesterol in the vertebrate retina

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