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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
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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.






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