Development of the rabbit retina. I. Size of eye and retina, and postnatal cell proliferation.

Measures of rabbit eyes and retinal wholemounts were used to evaluate the development of retinal area and shape. The retina is shown to have a horizontal axis about a third longer than the vertical axis just before birth, and to adopt an almost symmetrical shape during postnatal development to adulthood. In general, retinal thickness is shown to decrease after birth, but differently in particular retinal regions: the reduction is marked in the periphery, and less pronounced in the visual streak. As an exception, the myelinated region--after it becomes really myelinated, from 9 days p.p.--even increases in thickness. In all regions of the retina, the absolute and relative thickness of the nuclear layers decreases, whereas the relative thickness of plexiform and fibrous layers increases. Proliferation of cells within the rabbit retina was studied during the first three postnatal weeks. 3H-thymidine incorporation was used to demonstrate DNA synthesis autoradiographically in histological sections as well as in enzymatically isolated retinal cells. A first proliferation phase occurs in the neuroblastic cell layer and ceases shortly after birth in the retinal center, but lasts for about one week in the retinal periphery. We found, however, a few 3H-thymidine-labeled cells as late as in the third postnatal week. These late-labeled cells were found within the nerve fiber layer and in the inner plexiform layer. The latter cells were shown to express antigens detected by antibodies directed to the intermediate-sized filament protein vimentin, which are known to label Müller cells and neuroepithelial stem cells. This was confirmed in our preparation of enzymatically isolated cells; all cells with autoradiographically labeled nuclei revealed a characteristic elongated morphology typical for Müller radial glia (and also for early neuroepithelial stem cells). 3H-thymidine-labeled cells in the nerve fiber layer were most probably astrocytic. In analogy to the brain, we conclude that the mammalian retina undergoes a series of proliferation phases: first an early phase producing both neurons and glial cells, and then a late phase producing glial cells, e.g., in the nerve fiber layer. Most probably, the late phase within the inner nuclear layer is glial as well, i.e., consists of dividing Müller cells; it cannot be excluded, however, that there may remain some mitotically active stem cells.