Abstract
Purpose: :
The retinal pigment epithelium (RPE) is a multifunctional and indispensable component of the vertebrate retina. Its asymmetry, specialized membrane structures, and membrane motility, which are essential for many of its functions, rely heavily on a highly ordered cytoskeletons. At present, relatively little is known about the machinery and the molecular mechanism regulating cytoskeleton–mediated RPE functions. We found CLIC4, a recently identified actin–associated protein, was abundantly expressed in apical RPE microvilli. The purpose of these studies is to determine the functions of CLIC4 in RPE in vivo.
Methods: :
We performed CLIC4 silencing by transfecting siRNA (small interfering RNA) against CLIC4 into RPE of rodent eyes. RPE sheets or retina sections containing CLIC4–suppressed RPE were examined histologically and immunohistochemically.
Results: :
The CLIC4 suppressed RPE cells developed several morphological changes including microvillus shortening, cytoskeleton re–arrangement, and cell–cell contact breakdown. Moreover, these animals developed profound retinal detachment and photoreceptor dystrophy.
Conclusions: :
CLIC4 is a key molecule involved in the morphogenesis of RPE and its interdigit interaction with neural photoreceptors.
Keywords: retinal pigment epithelium • retinal adhesion • cell membrane/membrane specializations