Progressive Morphological and Functional Defects in Retinas From alpha1 Integrin-Null Mice

Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4647-54. doi: 10.1167/iovs.08-2011. Epub 2008 Jul 9.

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 alpha1beta1 integrin for retinal pigment epithelial cell homeostasis and retinal health was assessed by comparing alpha1 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 alpha1beta1 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 alpha1beta1 localizes to the basal aspect of retinal pigment epithelial cells colocalizing with the basal lamina of the RPE. Integrin alpha1-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 alpha1-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 alpha1beta1 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 alpha1beta1 function in retinal pigment epithelial and molecular defects in photoreceptor cell function before retinal abnormality is apparent.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arrestin / metabolism
  • Basement Membrane / metabolism
  • Basement Membrane / ultrastructure
  • Blotting, Western
  • Cell Count
  • Cell Line
  • Dark Adaptation
  • Fluorescent Antibody Technique, Indirect
  • Homeostasis / physiology
  • Humans
  • Integrin alpha1beta1 / physiology*
  • Mice
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Photoreceptor Cells, Vertebrate / ultrastructure*
  • Pigment Epithelium of Eye / metabolism*
  • Pigment Epithelium of Eye / ultrastructure
  • Presynaptic Terminals / ultrastructure*
  • Retinal Degeneration / metabolism*
  • Retinal Degeneration / pathology
  • Signal Transduction / physiology
  • Transducin / metabolism

Substances

  • Arrestin
  • Integrin alpha1beta1
  • Transducin