TY - JOUR
T1 - Progressive morphological and functional defects in retinas from α1 integrin-null mice
AU - Peng, You Wei
AU - Zallocchi, Marisa
AU - Meehan, Daniel T.
AU - Delimont, Duane
AU - Chang, Bo
AU - Hawes, Norman
AU - Wang, Weimin
AU - Cosgrove, Dominic
PY - 2008/10
Y1 - 2008/10
N2 - 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 α1β1 integrin for retinal pigment epithelial cell homeostasis and retinal health was assessed by comparing α1 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 α1β1 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 α-transducin was documented by immunohistochemical analysis of retinal cryosections. RESULTS. Integrin α1β1 localizes to the basal aspect of retinal pigment epithelial cells colocalizing with the basal lamina of the RPE. Integrin α1-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 α1-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 α1β1 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 α1β1 function in retinal pigment epithelial and molecular defects in photoreceptor cell function before retinal abnormality is apparent.
AB - 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 α1β1 integrin for retinal pigment epithelial cell homeostasis and retinal health was assessed by comparing α1 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 α1β1 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 α-transducin was documented by immunohistochemical analysis of retinal cryosections. RESULTS. Integrin α1β1 localizes to the basal aspect of retinal pigment epithelial cells colocalizing with the basal lamina of the RPE. Integrin α1-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 α1-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 α1β1 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 α1β1 function in retinal pigment epithelial and molecular defects in photoreceptor cell function before retinal abnormality is apparent.
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U2 - 10.1167/iovs.08-2011
DO - 10.1167/iovs.08-2011
M3 - Article
C2 - 18614805
AN - SCOPUS:53449085971
SN - 0146-0404
VL - 49
SP - 4647
EP - 4654
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 10
ER -