Growth and development of the mouse retinal pigment epithelium. I. Cell and tissue morphometrics and topography of mitotic activity

Abstract

A computer-assisted morphometric and kinetic analysis of retinal pigment epithelium (PE) development was carried out in C57BL/6J and hybrid mice from Embryonic Day 13 (E13) to Postnatal Day 250 (P250). Total cell number rose from 14,000 at E15 at the rate of about 4000 cells/day to P1 and then at about 1500 cells/day to reach a stable level of 54,000 cells at P15. Compared to the 4-fold rise in cell number, PE area increased about 10-fold, in part through cell hypertrophy which continued beyond P15. Cell concentration increased with distance from the optic nerve head during development, but the gradient disappeared by P20 except for a consistent population of small cells around the optic nerve head and a late-appearing population of very large cells at the ora serrata. Binucleate cells constitute 2.1% of the PE cell population at P1 and 26% at P30, almost all of them located in the posterior 75% of the PE where they comprise 70% of the cell population at some radial positions. Mitotic cells, detected by fluorescent monoclonal antibody R3, are distributed across the entire PE at E13. As the eye grows the mitotic zone occupies a progressively smaller and more distal proportion of the increasing radius; by P5 only the region near the ora serrata is highly active, with some additional mitotic cells trailing into a broad central zone. From P7 to P15 nuclear divisions persist only centrally to generate the youngest uninucleate and binucleate cells. The mouse PE thus shows a pattern of edge-biased interstitial growth (in contrast to amphibians with strict edge growth).