Extra Cellular Matrix Protein, Lysyl Oxidase, as a Therapeutic Target for Ocular Angiogenesis pp. 367-378
Authors: (K.N. Sulochana, K. Coral, Biochemistry Research Department, Vision Research Foundation, Sankara Nethralaya, Chennai, India)
Abstract: Abnormal angiogenesis is responsible for many human diseases and inhibiting angiogenesis is an important area of drug development. Angiogenesis, the development of new blood vessels from pre-existing vessels, is a multi-step process regulated by a variety of pro and antiangiogeneic molecules, which are potential targets for the development of drugs. Lysyl oxidase (LOX), a copper-containing amine oxidase known for its function in the maintenance of extracellular matrix integrity by catalyzing collagen and elastin cross linkages. Very recently, diverse roles have been attributed to Lysyl oxidase and these novel activities cover a spectrum of diverse biological functions such as developmental regulation, tumor suppression, cell migration, adhesion, apoptosis and cellular senescence. LOX expression has been shown to be regulated by hypoxia inducible factor-1, transforming growth factor β, tumor necrosis factor α, platelet derived growth factor, fibroblast growth factor and retinoic acid. The association of LOX in ocular pathology is currently being explored. Lowered levels of vitreous LOX has been reported in PDR and RRD. Increased choroidal neovascularization following laser induction in mice lacking Lysyl oxidase-like-1(LOXL-1) is also observed. Besides, mutations in a single gene LOXL-1 is responsible for exfoliation syndrome and exfoliative glaucoma. With the increasing flow of information in this area, it can be said that LOX is a central molecule for most of the angiogenesis related pathways and therapeutic agents influencing LOX activity will be a near future prospect for ocular angiogenesis related diseases.