Cell type differentiation dynamics in the developing porcine retina.

The dynamics of retinal embryogenesis have been well characterized previously in terms of cell proliferation, genesis and migration, whereas overall cell type differentiation within the retinal layers has been less thoroughly explored. In the present study, phenotypical differentiation of all 7 major retinal cell types was examined in the developing porcine retina using one cell-specific immunohistochemical marker per cell type. At the end of the first trimester at E39 (39 days after gestation), neurofilament labeled ganglion cells, recoverin labeled photoreceptors, vimentin labeled Müller cells and synaptophysin labeled presynaptic vesicles were found. Rhodopsin labeled rod photoreceptors were present at E60, whereas cone transducin labeled cone photoreceptors were not seen until E99. Differentiation of inner nuclear cells coincided with the appearance of the retinal layers at E70-E99 with the presence of parvalbumin labeled amacrine cells, calbindin labeled horizontal cells and PKC labeled rod bipolar cells. At postnatal day 4, all retinal subtypes except for cone photoreceptors displayed a labeling pattern corresponding to the one found in the adult porcine retina. The immunohistochemical labeling pattern suggests that phenotypic differentiation of the 7 principal retinal cell types in the porcine retina follows a central-to-peripheral spatio-temporal gradient similar to the one reported for cell proliferation and genesis. Differentiation of the non-laminated retinal cell mass appears to be initiated at its outer and inner margins and progresses inwards, a process which ends in the formation of the characteristic plexiform and nuclear layers. The dynamics of retinal cell type differentiation are of interest from a biological standpoint and are also important for therapeutical strategies in retinal degenerative disease.