defects in the outer limiting membrane are associated with rosette development in the nrl？？ retina缺陷限制外膜与玫瑰有关发展海军 视网膜.pdfVIP

Defects in the Outer Limiting Membrane Are Associated with Rosette Development in the Nrl 2/ 2 Retina Michael W. Stuck, Shannon M. Conley, Muna I. Naash* Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America Abstract The neural retinal leucine zipper (Nrl) knockout mouse is a widely used model to study cone photoreceptor development, physiology, and molecular biology in the absence of rods. In the Nrl2/ 2 retina, rods are converted into functional cone-like cells. The Nrl2/ 2 retina is characterized by large undulations of the outer nuclear layer (ONL) commonly known as rosettes. Here we explore the mechanism of rosette development in the Nrl2/ 2 retina. We report that rosettes first appear at postnatal day (P)8, and that the structure of nascent rosettes is morphologically distinct from what is seen in the adult retina. The lumen of these nascent rosettes contains a population of aberrant cells protruding into the subretinal space that induce infolding of the ONL. Morphologically adult rosettes do not contain any cell bodies and are first detected at P15. The cells found in nascent rosettes are photoreceptors in origin but lack inner and outer segments. We show that the adherens ¨ junctions between photoreceptors and Mu ller glia which comprise the retinal outer limiting membrane (OLM) are not uniformly formed in the Nrl2/ 2 retina and thus allow protrusion of a population of developing photoreceptors into the subretinal space where their maturation becomes delayed. These data suggest that the rosettes of the Nrl2/ 2 retina arise due to defects in the OLM and delayed maturation of a subset of photoreceptors, and that rods may play an important role in the proper form