Morphogenesis of the retinal pigment epithelium: toward understanding retinal degenerative diseases

Ann N Y Acad Sci. 1998 Oct 23;857:1-12. doi: 10.1111/j.1749-6632.1998.tb10102.x.

Abstract

The phenotype of an epithelial cell is defined by a unique combination of morphology, gene and protein expression, and protein localization. Results indicate that the terminal differentiation of the RPE cell can be described in part by changes in the polarity of its surface proteins alpha v beta 5 integrin, Na,K-ATPase, N-CAM, and EMMPRIN. Changes in protein/gene expression and protein localization in late stages of RPE development identify alpha v beta 5 integrin as a key player in RPE phagocytosis, and N-CAM and EMMPRIN as potentially important molecules in other RPE functions necessary for photoreceptor survival. By studying the trafficking of the later two proteins it is shown that entry into an apical or basolateral pathway in RPE cells cannot be predicted by the distribution of a given protein in other epithelial cells, and that this distribution may change through the course of RPE development. The mechanisms used by RPE and other epithelia to establish and maintain their specific polarity properties are fundamental to the formation and maintenance of their specific epithelial phenotype. The ability to therapeutically direct molecules incorporated into RPE by gene therapy into apical or basal surfaces requires an understanding of protein localization and expression. Furthermore, evidence is provided that assays capitalizing on changes in gene/protein expression and protein localization during the late stages of RPE development can prove a productive way of identifying proteins used by RPE for photoreceptor support. This approach can continue to be exploited to identify other proteins essential for the mission of the RPE cell, that may thus be likely candidates for participation in retinal degenerative disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aging
  • Animals
  • Antigens, CD*
  • Antigens, Neoplasm*
  • Basigin
  • Cell Polarity
  • Gene Expression Regulation, Developmental
  • Genetic Therapy
  • Humans
  • Integrins / genetics
  • Integrins / physiology
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Morphogenesis
  • Neural Cell Adhesion Molecules / genetics
  • Neural Cell Adhesion Molecules / physiology
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / embryology*
  • Pigment Epithelium of Eye / physiology
  • Receptors, Vitronectin*
  • Retinal Degeneration / physiopathology*
  • Retinal Degeneration / therapy
  • Sodium-Potassium-Exchanging ATPase / genetics
  • Sodium-Potassium-Exchanging ATPase / metabolism

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • BSG protein, human
  • Integrins
  • Membrane Glycoproteins
  • Neural Cell Adhesion Molecules
  • Receptors, Vitronectin
  • integrin alphaVbeta5
  • Basigin
  • Sodium-Potassium-Exchanging ATPase