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

Abstract

ABSTRACT 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.