Physiological Postnatal Neurogenesis, Development, and Maturation in the Regenerable Retina

The retina enlarges postnatally by ∼440% in axolotls and ∼150% in humans, predicting a reduction in neuron densities by 81.5% and 60%, respectively, if neurogenesis is absent. The concurrent retinal remodeling is poorly characterized. We studied retinas of 2-15 cm axolotls. Results showed that hatchling (∼2 cm) retinas, particularly the peripheral (Peri) had 1-2 more soma rows in the ganglion cell (GCL) layer and outer (ONL) and inner nuclear (INL) layers. Cell density reduced in GCL (GCs, -49%) in juveniles (4-12 cm) but increased in INL (74%) and ONL (55.5%) in young juveniles (4-6 cm), demonstrating intensive neurogenesis. Central retina (Cnt) in juveniles thickened (47 µm), and photoreceptor outer segments (OSs) elongated (32 µm). Peri of 2-6 cm animals possessed more undifferentiated cells (triangular doublecortin (DCX)+++; columnar DCX+/glutamine synthetase (GS)+ or DCX-/GS+) and higher density ratios of amacrine cells (ACs)/cones (4.4-2.1), bipolar cells (BCs)/cones (1.9-1.7), rods/cones (1.6-1), and GCs/cones (2-0.6), respectively, compared to 1.6-0.4 in Cnt; double-strand (ds) DNA signals of rods, horizontal cells, and putative OFFBCs in older animals resembled immature neurons. It suggests maturation sequences of GCL > ONL > INL, Cnt > Peri, and cone- and ON pathways > rod- and OFF pathways. S- and L/M-opsins peaked in juveniles, revealing L/M-opsin+ cones, S-opsin+ rods and cones, and weak-L/M-opsin+ rods of a thinner or thicker OS. Cx36 increased in 4-15 cm animals. GABA signals in late juveniles (7-12 cm) were maximal, light-enhanced, and revealed ACs, rod spherules, and Müller cells, suggesting stronger GABA release and transport. Thus, the retina undergoes critical post-hatch development, generating neurons and strengthening excitatory signaling, electrical coupling, and inhibitory regulation.