Genesis of the retinal pigment epithelium in the macaque monkey

The development of the retinal pigment epithelium (RPE) was studied in rhesus monkey (Macaca mulatta) fetuses, neonates, and juveniles exposed to a pulse of 3H-thymidine (3H-TdR) between embryonic day (E) 25 and postnatal day (P) 204 and examined at short and long intervals after the injection of the isotope. The RPE develops from the outer layer of the optic cup which by E45 consists of a multistratified epithelium. The outer layer appears immature near the retina's edge and gradually becomes monostratified and more mature centrally. Even at this early stage, all cells contain pigmented melanosomes, although peripherally the pigment is limited to the apical portion of the cells. Examination of autoradiograms from animals allowed to survive for several postnatal months shows that monkey RPE cell genesis begins just after E27, increasing to a peak frequency of 0.38 cells/mm at E43. Between E30 and E85 the density of radiolabelled cells varies within a restricted range of from 0.2 to 0.4 cells/mm (mean = 0.25 +/- 0.09). From the density of radiolabelled cells, and data on the overall density of RPE cells in the juvenile retina, we determined the labelling index. During the first half of gestation, between 0.38% and 0.99% (mean = 0.65 +/- 0.22) of RPE cells are generated during the short interval of isotope availability after pulse injection. Approximately 5% of RPE cells were generated by E33, and 50% by E71. After E85, RPE cytogenesis begins gradually to decrease, and 95% of the cells have been generated by the time of birth. Continued, very low density (0.01 cells/mm) cytogenesis in the RPE is seen at P17, and persists at least until seven months postnatally. RPE cell genesis begins near the fovea, and proceeds towards the periphery. Cell division largely ceases in both foveal and perifoveal regions by E56, at which time labelled cells first begin to appear peripheral to the equator. Besides the timing differences, RPE genesis in the central retina differs from that in the peripheral retina in that it proceeds at a higher rate, and lasts for a shorter time period. A prolonged postnatal period of low density RPE cell genesis persists in both central and peripheral retina. Comparison of the pattern of expansion of the area containing radiolabelled cells in the RPE and neuroretina demonstrates a remarkable spatial and temporal correspondence. Close analysis suggests that at any point on the retina, the last cells are generated in the neuroretina slightly before the last cells in the RPE.