Loss of the antiangiogenic pigment epithelium-derived factor in patients with angiogenic eye disease.
نویسندگان
چکیده
Retinal neovascularization characterizes proliferative diabetic retinopathy (PDR). Pigment epithelium-derived factor (PEDF) has been shown to be a major antiangiogenic growth factor in the mammalian eye. PEDF expression is suppressed by hypoxia, and changes in PEDF have been correlated to the development of retinal neovascularization in animal models of hypoxic eye disease. However, whether this concept of a reduced angiogenesis inhibitor holds true in humans is as yet unclear. In this study, we analyzed the in vivo regulation of PEDF in patients with and without hypoxic eye disease. We used immunoblots to measure PEDF in ocular fluids obtained from 64 nondiabetic and diabetic patients. In addition, immunohistochemistry of PEDF was carried out in specimens of normal human retinas and retinas with various degrees of diabetic retinopathy. The PEDF concentrations in patients with PDR (P < 0.001) or extensive nondiabetic retinal neovascularization caused by retinal-vein occlusion (P < 0.001) were lower than in control patients. Levels of PEDF were replenished in PDR patients with previous retinal scatter photocoagulation compared with PDR patients without previous photocoagulation (P = 0.01). Immunohistochemistry revealed an interstitial staining pattern as expected for a secreted protein, with an intense staining in retinas of patients without proliferative eye disease. However, in patients with PDR, little or no staining was detectable. Our data strongly support the concept that retinal angiogenesis is induced by loss of the major angiogenesis inhibitor in the eye, PEDF, in combination with an increased expression of angiogenic growth factors such as vascular endothelial growth factor. Our findings suggest that substitution of angiogenesis inhibitors may be an effective approach in the treatment of PDR.
منابع مشابه
Role of Pigment Epithelium-Derived Factor in Stem/Progenitor Cell-Associated Neovascularization
Pigment epithelium-derived factor (PEDF) was first identified in retinal pigment epithelium cells. It is an endogenously produced protein that is widely expressed throughout the human body such as in the eyes, liver, heart, and adipose tissue; it exhibits multiple and varied biological activities. PEDF is a multifunctional protein with antiangiogenic, antitumorigenic, antioxidant, anti-inflamma...
متن کاملPigment epithelium-derived factor: clinical significance in estrogen-dependent tissues and its potential in cancer therapy
Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the family of non-inhibitory serpins. The broad spectrum of PEDF biological activity is evident when considering its effects in promoting cell survival and proliferation, as well as its antiangiogenic, antitumor, and anti-metastatic properties. Although the structural domains of the PEDF gene that mediate such diverse ef...
متن کاملAnterior Segment Cornea Possible Role of Pigment-epithelium-derived Factor in Corneal Angiogenesis
The detection of pigment-epithelium-derived factor (PEDF) in corneal tissue has allowed greater understanding of the avascularity of corneal tissue. The ability of the cornea to maintain the avascular nature of this tissue, also referred to as the angiogenic privilege of the cornea, could be partly attributed to the presence of this factor. This privilege is severely impaired by various disease...
متن کاملAltered pigment epithelium-derived factor and vascular endothelial growth factor levels in lymphangioma pathogenesis and clinical recurrence.
OBJECTIVE To determine the role of angiogenesis in the clinical behavior and pathogenesis of lymphangioma tumors. DESIGN A retrospective study. Median follow-up period was 44.5 months. SETTING Children's Memorial Hospital, Chicago, Ill. PATIENTS Tumor specimens from 12 pediatric patients who underwent surgical excision of cervicofacial lymphangioma were examined for expression of angiogen...
متن کاملLong-Term PEDF Release in Rat Iris and Retinal Epithelial Cells after Sleeping Beauty Transposon-Mediated Gene Delivery
Pigment epithelium derived factor (PEDF) is a potent antiangiogenic, neurotrophic, and neuroprotective molecule that is the endogenous inhibitor of vascular endothelial growth factor (VEGF) in the retina. An ex vivo gene therapy approach based on transgenic overexpression of PEDF in the eye is assumed to rebalance the angiogenic-antiangiogenic milieu of the retina, resulting in growth regressio...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Diabetes
دوره 50 12 شماره
صفحات -
تاریخ انتشار 2001