The Role of Extra-cellular Matrix in Age-related Macular Degeneration
Author: Ngai Hang Victor Chong
Publisher:
Published: 2010
Total Pages: 328
ISBN-13:
DOWNLOAD EBOOKThere is increasing evidence to suggest that changes in the extracellular matrix (ECM) play an important role in the pathogenesis of age-related macular degeneration (AMD). These changes in ECM in AMD may be an exaggeration of the ECM alterations seen in aging. Similarly, AMD shares many clinical and pathological features with Sorsby's Fundus Dystrophy (SFD), an autosomal dominant disease associated with mutations in the gene for TIMP-3, a tissue inhibitor of metalloproteinases (MMPs), an important regulator of ECM. -- In an attempt to understand the role of ECM in AMD, this research initially focused on the expression of TIMP-3 in the Bruch's membrane in aging, SFD and AMD and its spatial correlation with ECM proteins and Bruch's membrane thickness. We found TIMP-3 are accumulated in Bruch's membrane in all three conditions and correlated well with the distribution of elastin and collagen VI tetramer. -- We developed an in vitro system to assess whether the expression of TIMPs and MMPs can be modified by cytokines and to determine whether deposits under the retinal pigment epithelium (RPE) could be modulated by the change of expression. Sub-RPE deposits developed in vitro shared similar ultrastructural changes to those seen in AMD and these deposits were modulated with retinal homogenate, TNF-a and MMP-2 providing proof of principle that RPE deposits can be formed and modified in vitro. -- We then studied the thickness and integrity of the elastic layer of the Bruch's membrane within the eye in both normal and AMD donors. The elastic layer has poor integrity in areas prone to have choroidal neovascularisation, a hallmark of neovascular AMD. This is more so in the case of AMD donors suggesting that the elastic layer may be a vital physical barrier for the invasion of these abnormal choroidal blood vessels.