Pigment epithelium-derived factor maintains retinal pigment epithelium function by inhibiting vascular endothelial growth factor-R2 signaling through gamma-secretase.

Wet age-related macular degeneration (AMD) attacks the integrity of the retinal pigment epithelium (RPE) barrier system. The pathogenic process was hypothesized to be mediated by vascular endothelial growth factor (VEGF) and antagonized by pigment epithelium-derived factor (PEDF). To dissect these functional interactions, monolayer cultures of RPE cells were established, and changes in transepithelial resistance were evaluated after administration of PEDF, placenta growth factor (VEGF-R1 agonist), and VEGF-E (VEGF-R2 agonist).

Multiple toxic effects of low-dose methotrexate in a patient treated for psoriasis.

Purpose: A case of toxicity encountered with low-dose methotrexate therapy is discussed.

Summary: A 59-year-old African American woman receiving long-term therapy for psoriasis came to the hospital with painful ulcers, difficulty swallowing, cutaneous lesions, and acute renal failure. Her medical history included type 2 diabetes mellitus, hypertension, coronary artery disease, morbid obesity, and psoriasis.

Systemic and periocular deliveries of plasminogen kringle 5 reduce vascular leakage in rat models of oxygen-induced retinopathy and diabetes.

Purpose: Increased retinal vascular permeability is a common complication of diabetes and a major cause of vision loss in diabetic patients. The current study is to determine the effect of plasminogen kringle 5 (K5) on vascular leakage via systemic and periocular deliveries.

Methods: Oxygen-induced retinopathy (OIR) was generated by exposing newborn rats to 75% oxygen.

The effect of angiostatin on vascular leakage and VEGF expression in rat retina.

Angiostatin is a potent angiogenic inhibitor. The present study identified a new activity of angiostatin: reducing vascular leakage, which is associated with diabetic macular edema, tumor growth and inflammation. An intravitreal injection of angiostatin significantly reduced retinal vascular permeability in rats with oxygen-induced retinopathy and in those with streptozotocin-induced diabetes, but not in normal rats.

Decreased pigment epithelium-derived factor and increased vascular endothelial growth factor levels in pterygia.

Purpose: Pterygia are histologically composed of proliferating fibrovascular tissue. This study compared expression levels of an angiogenic inhibitor, pigment epithelium-derived factor (PEDF), in pterygia with those in normal corneal and conjunctival tissues.

Methods: The normal human conjunctival and corneal tissues were obtained from surgery or from donor eyes without ocular diseases.

Difference in ischemic regulation of vascular endothelial growth factor and pigment epithelium--derived factor in brown norway and sprague dawley rats contributing to different susceptibilities to retinal neovascularization.

The present study compared susceptibilities of Sprague Dawley (SD) and Brown Norway (BN) rats with ischemia-induced retinal neovascularization. An exposure to constant hyperoxia followed by normoxia induced significant retinal neovascularization in BN rats but not in SD rats, as demonstrated by fluorescein retinal angiography, measurement of avascular area, and count of preretinal vascular cells. These results indicate a rat strain difference in susceptibility to retinal neovascularization.

Down-regulation of vascular endothelial growth factor and up-regulation of pigment epithelium-derived factor: a possible mechanism for the anti-angiogenic activity of plasminogen kringle 5.

We have previously shown that intravitreal injection of plasminogen kringle 5 (K5), a potent angiogenic inhibitor, inhibits ischemia-induced retinal neovascularization in a rat model. Here we report that K5 down-regulates an endogenous angiogenic stimulator, vascular endothelial growth factor (VEGF) and up-regulates an angiogenic inhibitor, pigment epithelium-derived factor (PEDF) in a dose-dependent manner in vascular cells and in the retina. The regulation of VEGF and PEDF by K5 in the retina correlates with its anti-angiogenic effect in a rat model of ischemia-induced retinopathy.