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Tierexperimentelle untersuchungen zur rolle von entzündungsmediatoren bei der hornhautneovaskularisation

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Abstract

Experimental investigations concerning the role of inflammatory compounds in corneal neovascularization.

Natural and synthetic inflammatory compounds were implanted in the corneas of rabbits to clarify the question whether corneal neovascularization is induced by stromal edema alone, or by neovascular mediators. It could be demonstrated that prostaglandin E1 and E2 have an angiogenetic capacity, whereas their precursor (arachidonic acid) as well as PGA1, A2, B2, I2 and Thromboxan A2 were inactive in this regard.

Histology showed that corneal neovascularization is always accompanied by the invasion of polymorphonuclear leukocytes. Corneal edema in the beginning of vascularization can be explained by the activities of PGE (vasodilation, increase of vascular permeability, liberation of histamine). The implantation of lipoxygenase-dependent arachidonic acid compounds (5-HETE, Leukotriene B4) demonstrated that these mediators share in the process of neovascularization by inducing the chemotaxis. The above mentioned activities of prostaglandins and leukotrienes could also be demonstrated following penetrating keratoplasty and alkali burns of the anterior segment inducing extensive corneal neovascularization. An analysis of the prostaglandin- and leukotriendependent mechanisms could be achieved by selective PG- and LT- inhibitors. Radioimmunoassays showed a definite correlation between the concentrations of PGE and the amount of neovascularization following alkali burns. The results of our research lead to the following scheme of pathophysiology of corneal neovascularization: hypoxic, chemical, thermic and mechanical alterations of the cornea induce an activation of corneal cytomembranes, thus initiating (1) the cyclooxygenase-dependent synthesis of prostaglandins with consecutive vasodilation and increase of vascular permeability as well as histamine liberation resulting in corneal edema; on the other hand, prostaglandins proved to have a minimal chemotactic activity; (2) the lipoxygenase-dependent synthesis of leukotrienes inducing chemotaxis and diapedesis of polymorphonuclear leukocytes into the corneal stroma. These inflammatory cells are then the main source of newly synthesized leukotrienes maintaining the chemotaxis, and prostaglandins with angiogenetic activity. Cyclooxygenase- and lipoxygenase- inhibitors can inhibit these activities at two different levels, leading to an approach of successful therapy of corneal dieases inducing neovascularization.

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  1. Augenklinik, Johannes Gutenberg-Universität, Langenbeckstrasse 1, D-65, Mainz, BRD

    R. Rochels

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Rochels, R. Tierexperimentelle untersuchungen zur rolle von entzündungsmediatoren bei der hornhautneovaskularisation. Doc Ophthalmol 57, 215–262 (1984). https://doi.org/10.1007/BF00143085

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