We investigated gene expression profiles of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) in differentiated and non-differentiated retinal pigment epithelial (RPE) cells during oxidative stress. Human RPE cells were grown in culture on laminin-coated flasks to obtain differentiated features. Cells cultured on plastic were used as non-differentiated controls. After confluence, hydrogen peroxide (H2O2) was added for 48 h, then, total RNA was extracted and used for RT-PCR and Northern blot analysis. Medium conditioned by RPE was used for ELISA, Western blotting, and in vitro angiogenesis assay. As a result, differentiated RPE cells expressed significantly higher levels of VEGF protein, as compared to their non-differentiated counterparts. The expression pattern remained consistent even after cellular exposure to H2O2. Conversely, while elevated levels of PEDF transcript and protein were seen in differentiated RPE cells, compared to non-differentiated cells, a marked decrease at both PEDF mRNA and protein levels was seen after treatment with H2O2. Moreover, this decrease in PEDF expression was dosage dependent. In in vitro angiogenesis assay, conditioned medium from differentiated human RPE cells after exposure to H2O2 showed a dramatic increase in tubular formation and migratory activity of microvascular endothelial cells. These data suggest that, in physiological conditions, a critical balance between PEDF and VEGF exists, and PEDF may counteract the angiogenic potential of VEGF. Under oxidative stress, PEDF decreases disrupting this balance. This equilibrium shift may be significant in promoting a pathological condition of RPE cells and contributing to choroidal neovascularization in age-related macular degeneration.
MMP-2 may be essential in the regulation of retinal neovascularization. Pharmacologic intervention using MMP inhibitors may be a future therapeutic approach for angiogenic retinal diseases.
ABSTRACT.Background: Acquired retinal macroaneurysms are round dilatations of retinal arterioles that occur in the posterior fundus. They tend to rupture before they grow large and cause a visual decrease. The average diameter of macroaneurysms in the previous reports is 281 micrometer. Methods: A 63-year-old man complained of a sudden decrease of visual acuity in the left eye. Fundus examination of his left eye revealed a large protruded mass, 2 disc diameters in size, at the first bifurcation of the inferotemporal retinal artery. Preretinal vitreous bleeding and serous retinal detachment were observed around the lesion. Indocyanine green (ICG) angiography showed this mass to be continuous with the inferotemporal retinal artery and ICG dye leaked from the retinal artery into the lumen of the mass, with pulsation. Results: Six months later, the large macroaneurysm underwent spontaneous involution. Conclusion: As shown in this patient, retinal macroaneurysms may grow extremely large. ICG angiography was useful to diagnose this large retinal arterial macroaneurysm.
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