부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.matbio.2009.02.004 Byline: Xiaoyang Bai, David J. Dilworth, Yi-Chinn Weng, Douglas B. Gould Keywords: Type IV collagen; Basement membrane; Ocular development Abbreviations: BM, basement membrane; DIC, differential interference contrast; ILM, inner limiting membrane; ICA, iridocorneal angle; RPE, retinal pigment epithelium Abstract: Type IV collagens are the most abundant proteins in basement membranes. Distinct genes encode each of six isoforms, [alpha]1(IV) through [alpha]6(IV), which assemble into one of three characteristic heterotrimers. Disease-causing mutations in each of the six genes are identified in humans or mice and frequently include diverse ocular pathogenesis that encompass common congenital and progressive blinding diseases, such as optic nerve hypoplasia, glaucoma, and retinal degeneration. Understanding where and when collagen IV molecules are expressed is important because it defines limits for the location and timing of primary pathogenesis. Although localization of collagen IV isoforms in developed human eyes is known, the spatial and temporal distribution of type IV collagens throughout ocular development has not been determined in humans or in mice. Here, we use isoform-specific monoclonal antibodies to systematically reveal the localization of all six collagen IV isoforms in developing mouse eyes. We found that [alpha]1(IV) and [alpha]2(IV) always co-localized and were ubiquitously expressed throughout development. [alpha]3(IV) and [alpha]4(IV) also always co-localized but in a much more spatially and temporally specific manner than [alpha]1(IV) and [alpha]2(IV). [alpha]5(IV) co-localized both with [alpha]3(IV)/[alpha]4(IV), and with [alpha]6(IV), consistent with [alpha]5(IV) involvement in two distinct heterotrimers. [alpha]5(IV) was present in all basement membranes except those of the vasculature. [alpha]6(IV) was not detected in vasculature or in Bruch's membrane, indicating that [alpha]5(IV) in Bruch's membrane is part of the [alpha]3[alpha]4[alpha]5 heterotrimer. This comprehensive analysis defines the spatial and temporal distribution of type IV collagen isoforms in the developing eye, and will contribute to understanding the mechanisms underlying collagen IV-related ocular diseases that collectively lead to blindness in millions of people worldwide. Author Affiliation: Departments of Ophthalmology and Anatomy, Institute of Human Genetics, University of California, San Francisco, CA 94143, United States Article History: Received 6 November 2008; Revised 20 February 2009; Accepted 24 February 2009