Inhibitors of corneal inflammation and angiogenesis : Prospectives and challenges

Abstract

row: photography of vessels in a cornea (false colours); computer elaboration of the vessels; HE histology of cornea with vessels and inflammatory cells; middle row: vessels and inflammatory cells seen with IVCM; lower row: HUVEC cells stained for VEGF; immunofluorescence of neovascularized cornea stained for CD31 and NFκB. Other illustrations in the thesis by Anthony Mukwaya, Per Lagman, Pierfrancesco Mirabelli. This thesis contains original material, and material reprinted from previously published work, published under a CC BY license (Creative Commons Attribution 4.0 International License), which allows for maximum dissemination and re-use of open access materials. IKE, Linköping university iv v …Instruction, and not silver; and Knowledge rather than choice gold. For Wisdom is better than rubies… (Proverbs 8: 10-11) vi vii ABSTRACT Pathologic angiogenesis is involved in cancer and several blinding conditions such as wet age-related macular degeneration, proliferative retinopathies and corneal neovascularization. In these dieseases, the angiogenic triggers are hypoxia and inflammation, and both involve the main angiogenic mediator, which is Vascular Endothelial Growth Factor (VEGF). Among available treatments, anti-VEGF often shows limited or temporary efficacy, while steroids are potentially responsible for many side-effects. This thesis presents a series of linked studies aimed at elucidating the early pathologic changes leading to inflammation and corneal neovascularization, and how various treatments affect this process. In this thesis, xii xiii LIST OF PUBLICATIONS INCLUDED IN THE THESIS PAPER I Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model. Mirabelli P, Peebo BB, Xeroudaki M, Koulikovska M, Lagali N. Exp Eye Res.

Tumor Angiogenesis and Anti-Angiogenic Strategies for Cancer Treatment

“…As previously mentioned, angiogenesis is the physiological process involved in the formation of blood vessels from pre-existing ones. Although it primarily occurs in embryonal and fetal development, it can also happen in adults, in the context of physiological adaptations, such as wound healing, muscle growth, organ lining regeneration, menstrual cycle through the growth of the endometrium, and placenta growth [16,17].…”

“…Angiogenesis is the dynamic process through which new blood vessels are formed from pre-existing ones [16]. There are three types of angiogenesis, namely sprouting angiogenesis, which is the most common, intussusception or splitting angiogenesis, where a new wall grows inside an existing vessel, eventually dividing into two vessels, and looping angiogenesis, where vessel loops are mechanically dragged into the tissue [16,17].…”

“…The initial step involved in angiogenesis involves the action of an angiogenic stimulus, such as hypoxia or inflammation [17]. Subsequently, a cascade of biochemical events are generated, and the repair of damaged vessels or the formation of the new vessel will be rigorously regulated by specific chemical signals, which are proteins known as angiogenic activators or inhibitors, that coordinate the functions of endothelial and smooth muscle cells [25,26].…”

Endocannabinoids and related compounds as modulators of angiogenesis: Concepts and clinical significance

“…Nevertheless, uncontrolled and/or pathological angiogenesis can result in development and progression of multiple types of cancers, as well as different ocular disorders, including diabetes‐associated retinopathies. Consequently, understanding angiogenesis and its manipulation utilizing different pharmacological agents is of great importance in medicine for treatment of a range of pathological disorders 2–5 …”

Investigation the Association of the VEGFR-2 and -2578C\A Polymorphism as a Risk Factor for Incidence of Lung Cancer in Babylon Province

“…VEGFR-2 is a type V receptor tyrosine kinase mainly known to be expressed in vascular endothelial cells and encoded by theKDR gene [10] . This receptor responds to the signal of VEGF binding, which initiates a phosphorylation cascade that ultimately involves nuclear regulatory targets resulting in enhancement of endothelial proliferation, angiogenesis and cell migration [11] .The VEGF gene is located at chromosome 6p21.3, covering14 kb in length with 8 exons and 7 introns [12] .Being highly polymorphic, about 30 single SNPs have beenidentified and described [13] .Several SNPs of VEGF havebeenreported to be associated with individual susceptibilityto cancer and can alter the VEGF expression and proteinproduction [14][15][16][17][18][19][20] .…”