Kenneth P. Mitton, PhD FARVO
Eye Research Institute – Oakland University
For eye researchers of mammalian retinal development, rodent models are commonly used, especially mouse models. The relative timing of retinal cell type formations and arragement of mature retinal layers occur in the same relative sequence in most mammals. For those born with fully developed retinas and open eyes, like humans, the retinal development is completed by full term birth. For animals like mice, rats, and cats that are born with closed eyes for about 10-14 days, the retina is still in development. Mice and rats fall in the later category. This makes retina research easier, and in some cases simply possible, because we can carry out research on retinal development in rodents. The following information should be kept handy as a guide to the sequence of retinal development in mice and timing. Gestation in mice is about 19 days, with birth happening about this time, often called postnatal day zero (P0). Embryonic days are refered to as E11, E14 and so on.
While the retina is considered adult like by P21 in the mouse, there is still some elongation of the photoreceptor outer segments that progresses until about P30. In my lab I have personally confirmed that I can detect a reasonable small ERG at about age P14. This ERG, the A and B waves are much larger in amplitude by age P21.
The timings listed below are taken from the following excellent book:
Smith, RS, Kao, W. W.-Y., and John S.W.M. (2002) Chapter 3 Ocular Development. From Systematic Evaluation of the Mouse Eye: Anatomy, Pathology, and Biomethods. Pp 45-63.
The two neuroepithelial layers of the optic cup show differentiated proliferation with the inner neuroepithelial layer rapidly forming a multi-cellular inner layer. Axons from retinal ganglion cells start to exit the eye. (E11.5) the pre-neural retinal layer develops an acellular region adjacent to the future vitreous cavity.
Now the single primative neuroblastic layer is divided into inner and outer neuroblastic layers as seen by density of nuclear staining.
The inner and outer neuroblastic layers are more differentiated and thicker. In the central retina the neuroblastic layers begin to show a nuclear-free zone of separation. Cells of the inner neuroblastic layer are destined to form ganglion cells and those of the outer neuroblastic layer are destined to form photoreceptor, bipolar, amacrine and Muller cells.
The inner and outer limiting membrane is present by birth. The two neuroblast layers are separated. The outer neuroblastic layer starts to separate into the future inner and outer nuclear layers.
The outer nuclear layer shows differential staining into future inner and outer nuclear divisions but they are not yet separated by a plexiform space. Rudimentary photoreceptor inner segments are forming. (P0 is the time point of maximal terminal mitosis rate of progenitors destined to become rod cells).
Still NO outer plexiform layer formed yet. Inner segments are present at the posterior retina but there are no outer segments yet.
Outer plexiform layer formed clearly at the posterior retina. (highest rates of apoptosis are over.) Looks like the adult retina layer pattern but all nuclear layers are thicker than in the adult still. Ganglion cell layer has thinned. Inner segments are present.
All retinal layers formed from the posterior around to the periphery. By P14 apoptosis and thinning is greatly diminished. P10 some outer segment formation started. P14 to P21 outer segments will continue to grow in length to adult state.