Progressive morphological and functional defects in retinas from α1 integrin-null mice

You Wei Peng, Marisa L Zallocchi, Daniel T. Meehan, Duane Delimont, Bo Chang, Norman Hawes, Weimin Wang, Dominic E Cosgrove

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4647-4654
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Volume49
Issue number10
DOIs
StatePublished - Oct 1 2008

Fingerprint

Integrins
Retina
Basement Membrane
Transducin
Retinal Pigments
Epithelial Cells
Arrestin
Retinal Rod Photoreceptor Cells
Light
Photoreceptor Cells
Retinal Degeneration
Transmission Electron Microscopy
Knockout Mice
Cell Communication
Histology
Homeostasis
Western Blotting
Maintenance
Health

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Progressive morphological and functional defects in retinas from α1 integrin-null mice. / Peng, You Wei; Zallocchi, Marisa L; Meehan, Daniel T.; Delimont, Duane; Chang, Bo; Hawes, Norman; Wang, Weimin; Cosgrove, Dominic E.

In: Investigative Ophthalmology and Visual Science, Vol. 49, No. 10, 01.10.2008, p. 4647-4654.

Research output: Contribution to journalArticle

Peng, You Wei ; Zallocchi, Marisa L ; Meehan, Daniel T. ; Delimont, Duane ; Chang, Bo ; Hawes, Norman ; Wang, Weimin ; Cosgrove, Dominic E. / Progressive morphological and functional defects in retinas from α1 integrin-null mice. In: Investigative Ophthalmology and Visual Science. 2008 ; Vol. 49, No. 10. pp. 4647-4654.
@article{73fede56ae9a482fad5e777b7dfd8d20,
title = "Progressive morphological and functional defects in retinas from α1 integrin-null mice",
abstract = "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.",
author = "Peng, {You Wei} and Zallocchi, {Marisa L} and Meehan, {Daniel T.} and Duane Delimont and Bo Chang and Norman Hawes and Weimin Wang and Cosgrove, {Dominic E}",
year = "2008",
month = "10",
day = "1",
doi = "10.1167/iovs.08-2011",
language = "English (US)",
volume = "49",
pages = "4647--4654",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "10",

}

TY - JOUR

T1 - Progressive morphological and functional defects in retinas from α1 integrin-null mice

AU - Peng, You Wei

AU - Zallocchi, Marisa L

AU - Meehan, Daniel T.

AU - Delimont, Duane

AU - Chang, Bo

AU - Hawes, Norman

AU - Wang, Weimin

AU - Cosgrove, Dominic E

PY - 2008/10/1

Y1 - 2008/10/1

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.

UR - http://www.scopus.com/inward/record.url?scp=53449085971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=53449085971&partnerID=8YFLogxK

U2 - 10.1167/iovs.08-2011

DO - 10.1167/iovs.08-2011

M3 - Article

C2 - 18614805

AN - SCOPUS:53449085971

VL - 49

SP - 4647

EP - 4654

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 10

ER -