Abstract/Details

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


2004 2004

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Abstract (summary)

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.

Indexing (details)


Subject
Molecular biology;
Ophthalmology
Classification
0307: Molecular biology
0381: Ophthalmology
Identifier / keyword
Health and environmental sciences; Biological sciences; Aging; Cataracts; Lens
Title
Identification and functional characterization of cataract-specific gene expression changes reveals important pathways for human lens maintenance, aging and disease
Author
Hawse, John R., IV
Number of pages
211
Publication year
2004
Degree date
2004
School code
0256
Source
DAI-B 65/11, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780496125692, 0496125699
Advisor
Kantorow, Marc
University/institution
West Virginia University
University location
United States -- West Virginia
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3152264
ProQuest document ID
305113216
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305113216
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