Renno RZ, Youssri AI, Michaud N, et al. Expression of pigment epithelium-derived factor in experimental choroidal neovascularization

Angiogenesis Laboratory, Retina Research Institute, Massachusetts Eye and Ear Infirmary, 245 Charles Street, Boston, MA 02114, USA.
Investigative Ophthalmology &amp Visual Science (Impact Factor: 3.4). 06/2002; 43(5):1574-80.
Source: PubMed

ABSTRACT To investigate the expression of pigment epithelium-derived factor (PEDF) in the rat laser-injury model of choroidal neovascularization (CNV).
Retinas were immunostained for PEDF at different times (1, 2, and 3 weeks) after laser injury. Levels of PEDF protein in the vitreous at 1, 3, 7, 14, and 28 days after laser injury were also assayed by Western blot.
Protein levels of PEDF in the vitreous were increased during the first 7 days after CNV induction. Immunostaining for PEDF was observed throughout normal nonlasered control retinas, sham-lasered retinas, and areas remote to laser lesions, which were generally more intense in the outer nuclear layer (ONL) and less intense in the internal nuclear layer (INL). Decreased expression of PEDF was observed in flanking areas adjacent to the injury site and was confined mainly to the ONL. In the injury sites, immunostaining within the ONL was either absent or decreased for up to 3 weeks after laser injury (the duration of the study). Preadsorption of the anti-PEDF antibody with the immunizing peptide blocked specific labeling in the retina.
These results demonstrate an inverse correlation of expression of PEDF and formation of CNV in the experimental model and suggest that decreased expression of PEDF plays a permissive role in the formation of CNV. PEDF analogues may be a reasonable treatment strategy for CNV.

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    • "Although degeneration times vary in different experimental conditions, I/R-induced injury and retinal degeneration is initially observed primarily in inner retinal layers [e.g. the inner plexiform layer (IPL) and inner nuclear layer (INL)] that are supplied by the central retinal artery, in contrast to the outer nuclear layer (ONL) that is generally less affected [18-21]. Differently from inner retinal layers, the choroid supplies blood and nutrients to the photoreceptors and ONL [22,23]. This structural difference may influence the initiation stage of I/R injury. "
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    • "PEDF synthesis is upregulated under hyperemic conditions and downregulated in hypoxia.67 PEDF levels have been found to be low within choroidal neovascular tissues,68,69 and expression of PEDF is inversely correlated with the formation of CNVM in animal models.70 "
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    • "Second, vitreous PEDF concentrations were found to be significantly decreased in eyes with exudative AMD [16]. Additional evidence comes from an animal laser injury model showing an inverse correlation between PEDF expression and formation of choroidal neovascularizations [17,18]. Finally, the administration of recombinant natural PEDF or adenoviral vector-delivered PEDF has been found either to inhibit the development of choroidal neovascularizations or to reduce its extent [19–21]. "
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