Identification and functional characterization of cataract-specific gene expression changes reveals important pathways for human lens maintenance, aging and disease.

摘要

Human age-related cataract, and opacity of the eye lens, is a multifactorial disease with a poorly understood etiology and is the leading cause of world blindness and low vision. It has been estimated that any therapy that could delay the onset of age-related cataract by ten years would halve the number of individuals requiring surgery in their lifetime. To accomplish such a feat, it is essential to understand the molecular mechanisms and biological pathways associated with this disease. Here, I describe the global gene expression profiles of human age-related cataracts compared to clear lenses, differentiate these changes from those that occur with aging of the human lens, cluster the identified genes to reveal functional pathways altered in this disease, characterize a family of proteins in lens epithelial cells that respond to the presence of toxic metals known to be associated with cataract formation and implicate an important role for the methionine sulfoxide reductase A enzyme in protecting lens cells against oxidative stress damage. The results of the present work indicate that human age-related cataract is associated with multiple, previously identified, and novel lens epithelial gene expression changes and provide evidence that these changes are likely to be specific for cataract and not due to aging of the lens, have identified multiple genes that respond to the presence of insults associate with human cataract and implicate an important role for specific genes in the maintenance of lens transparency. Together, these data provide the foundation for some of the molecular events associated with human age-related cataract, categorize multiple pathways that may play critical roles in the development of cataract and provide evidence for essential functions of specific genes in protecting lens cells against oxidative stress.