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      Antiangiogenic Activity in Tears: Presence of Pigment-Epithelium-Derived Factor


      Ophthalmic Research

      S. Karger AG

      Growth factors, Tear fluid, Corneal neovascularization, Pigment-epithelium-derived factor

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          Background/Purpose: Pigment-epithelium-derived factor (PEDF) is of major importance to prevent neovascularization of the retina. Recently found to occur in the cornea and conjunctival tissue, its presence in tears has this far not been reported. Initial results, based on the analysis of diluted tear fluid samples, even indicated the absence of this factor in human tears. Considering the clinical importance of PEDF as regulator of corneal vascularization, we investigated undiluted human tears. Methods: Samples of 18 healthy individuals were collected and analyzed using a commercial ELISA. Samples were also collected from 5 patients with pterygium and as a positive control 2 samples of subretinal fluid from patients following retinal detachment surgery. Results: PEDF concentrations were below the detection limit (i.e. <0.1 ng/ml) in the majority of samples from the healthy individuals. However, PEDF was discovered in 3 of the samples taken, with significant concentrations of 2, 32 and 53 ng/ml. In the group of 5 patients with pterygium, there were no detectable concentrations of PEDF. Conclusion: PEDF may be found in measurable amounts in human tear fluid of healthy individuals and may therefore play a role in the effects and regulation of PEDF at the ocular surface.

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          Most cited references 3

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          Growth factors in the anterior segment: role in tissue maintenance, wound healing and ocular pathology.

          A number of growth factors and their associated receptors, including epidermal growth factor, transforming growth factor-beta, keratinocyte growth factor, hepatocyte growth factor, fibroblast growth factor and platelet-derived growth factor have been detected in the anterior segment of the eye. On binding to cellular receptors, these factors activate signalling cascades, which regulate functions including mitosis, differentiation, motility and apoptosis. Production of growth factors by corneal cells and their presence in the tear fluid and aqueous humour is essential for maintenance and renewal of normal tissue in the anterior eye and the prevention of undesirable immune or angiogenic reactions. Growth factors also play a vital role in corneal wound healing, mediating the proliferation of epithelial and stromal tissue and affecting the remodelling of the extracellular matrix (ECM). These functions depend on a complex interplay between growth factors of different types, the ECM, and regulatory mechanisms of the affected cells. Imbalances may lead to deficient wound healing and various ocular pathologies, including edema, neovascularization and glaucoma. Growth factors may be targeted in therapeutic ophthalmic applications, through exogenous application or selective inhibition, and may be used to elicit specific cellular responses to ophthalmic materials. A thorough understanding of the mechanism and function of growth factors and their actions in the complex environment of the anterior eye is required for these purposes. Growth factors, their function and mechanisms of action as well as the interplay between different growth factors based on recent in vitro and in vivo studies are presented.
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            Decreased pigment epithelium-derived factor and increased vascular endothelial growth factor levels in pterygia.

            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. The normal human conjunctival and corneal tissues were obtained from surgery or from donor eyes without ocular diseases. Pterygia were excised by therapeutic surgery under a microscope. Pigment epithelium-derived factor and vascular endothelial growth factor (VEGF) were measured by Western blot analysis. Their cellular localizations were determined by immunohistochemistry. Intensive PEDF immunostaining was detected in all the normal corneal and conjunctival samples analyzed, predominantly in the epithelium and endothelium of the cornea and in the epithelium of the limbus and conjunctiva. Under the same immunostaining conditions, pterygial samples showed negative or faint PEDF staining. In contrast, the same pterygial samples all showed intensive VEGF staining, predominantly in the epithelium and in blood vessels. Western blot analysis confirmed that the average PEDF level in pterygia was drastically lower than those in normal corneal and conjunctival tissues, respectively. In contrast, the VEGF level in pterygia was significantly higher than in the normal tissues. Pterygia exhibit significantly lower PEDF but higher VEGF levels than those in normal corneas and conjunctivae. The decreased PEDF level in pterygia may play a role in the formation and progression of pterygia.
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              Effects of the Schirmer test on the fibrinolytic system in the tear fluid


                Author and article information

                Ophthalmic Res
                Ophthalmic Research
                S. Karger AG
                December 2007
                20 November 2007
                : 40
                : 1
                : 16-18
                Laboratory of DOHF, St. Erik’s Eye Hospital, Karolinska Institutet, Stockholm, Sweden
                111153 Ophthalmic Res 2008;40:16–18
                © 2007 S. Karger AG, Basel

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                Page count
                References: 6, Pages: 3
                Original Paper


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