Title:Molecular Mechanisms of Complement System Proteins and Matrix Metalloproteinases in the Pathogenesis of Age-Related Macular Degeneration
VOLUME: 19 ISSUE: 10
Author(s):Naima Mansoor, Fazli Wahid, Maleeha Azam, Khadim Shah, Anneke I. den Hollander, Raheel Qamar and Humaira Ayub*
Affiliation:Department of Biotechnology, COMSATS University Islamabad, Abbottabad Campus, 22060, Department of Biotechnology, COMSATS University Islamabad, Abbottabad Campus, 22060, Department of Biosciences, COMSATS University Islamabad, Department of Biotechnology, COMSATS University Islamabad, Abbottabad Campus, 22060, Department of Ophthalmology, Radboud University Nijmegen Medical Centre, Nijmegen, Department of Biosciences, COMSATS University Islamabad, Department of Biotechnology, COMSATS University Islamabad, Abbottabad Campus, 22060
Keywords:Higher age diseases, drusen formation, genetics based pathogenesis, AMD therapeutics, complement
involvement in AMD, matrix metalloproteinases.
Abstract:Age-related macular degeneration (AMD) is an eye disorder affecting
predominantly the older people above the age of 50 years in which the macular
region of the retina deteriorates, resulting in the loss of central vision. The key
factors associated with the pathogenesis of AMD are age, smoking, dietary,
and genetic risk factors. There are few associated and plausible genes involved
in AMD pathogenesis. Common genetic variants (with a minor allele frequency
of >5% in the population) near the complement genes explain 40–60% of the
heritability of AMD. The complement system is a group of proteins that work
together to destroy foreign invaders, trigger inflammation, and remove debris
from cells and tissues. Genetic changes in and around several complement
system genes, including the CFH, contribute to the formation of drusen and
progression of AMD. Similarly, Matrix metalloproteinases (MMPs) that are
normally involved in tissue remodeling also play a critical role in the
pathogenesis of AMD. MMPs are involved in the degradation of cell debris and
lipid deposits beneath retina but with age their functions get affected and result
in the drusen formation, succeeding to macular degeneration. In this review,
AMD pathology, existing knowledge about the normal and pathological role of
complement system proteins and MMPs in the eye is reviewed. The scattered
data of complement system proteins, MMPs, drusenogenesis, and
lipofusogenesis have been gathered and discussed in detail. This might add
new dimensions to the understanding of molecular mechanisms of AMD
pathophysiology and might help in finding new therapeutic options for AMD.
