IOVS Blood
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1167/iovs.08-2011 on July 9, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:4647-4654.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-2011
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
iovs.08-2011v1
49/10/4647    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via ISI Web of Science (1)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Peng, Y.-W.
Right arrow Articles by Cosgrove, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Peng, Y.-W.
Right arrow Articles by Cosgrove, D.

Progressive Morphological and Functional Defects in Retinas from {alpha}1 Integrin-Null Mice

You-Wei Peng,1 Marisa Zallocchi,1 Daniel T. Meehan,1 Duane Delimont,1 Bo Chang,2 Norman Hawes,2 Weimin Wang,1 and Dominic Cosgrove1

1From the Boys Town National Research Hospital, Omaha, Nebraska; and 2The Jackson Laboratories, Bar Harbor, Maine.

PURPOSE. The role of integrin/cell matrix interactions between the RPE and the basement membrane in retinal maintenance and function is not well characterized. In this study the functional importance of {alpha}1β1 integrin for retinal pigment epithelial cell homeostasis and retinal health was assessed by comparing {alpha}1 integrin knockout mice with strain- and age-matched wild-type mice.

METHODS. Immunolocalization and Western blot analysis of retinas and ARPE19 cells were performed to examine the expression of {alpha}1β1 integrin in the RPE. Retinal abnormality was assessed by funduscopy, histology, and transmission electron microscopy. Progressive retinal damage was quantified by direct counting of rod photoreceptors. Light-induced translocation of arrestin and {alpha}-transducin was documented by immunohistochemical analysis of retinal cryosections.

RESULTS. Integrin {alpha}1β1 localizes to the basal aspect of retinal pigment epithelial cells colocalizing with the basal lamina of the RPE. Integrin {alpha}1-null mice have delayed-onset progressive retinal degeneration associated with thickening of the basement membrane, dysmorphology of basal processes, synaptic malformations, and funduscopic abnormalities. Integrin {alpha}1-null mice display marked delays in transducin translocation compared with dark-adapted wild-type mice after exposure to light.

CONCLUSIONS. Collectively, these data suggest an essential role for {alpha}1β1 integrin/basement membrane interactions in the RPE in basement membrane metabolism and translocation of transducin in photoreceptors. This is the first report describing evidence supporting an essential role for integrin/basement membrane interaction in the RPE. Further, this report demonstrates a direct link between integrin {alpha}1β1 function in retinal pigment epithelial and molecular defects in photoreceptor cell function before retinal abnormality is apparent.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Association for Research in Vision and Ophthalmology