Morphological Comparison of Human Midgestational and Mouse Postnatal Retinal Development.

Abstract

Understanding retinal development is important for better explaining retinal function and disease and as a model for generating retinal organoids and retinal regeneration strategies. Although development of mouse retina is studied in great detail, timing of retinal cell type development in humans is still poorly understood. This study aims to compare developmental steps in the human midgestational and mouse early postnatal retinas and to establish timeline correspondents and their anatomical landmarks. Immunofluorescence analysis of retinal cryosections was performed on human retinas collected from fetuses of 15 to 27 gestational weeks (GW15-GW27) and mouse retina from pups ranging from 0 to 14 days (P0-P17). Markers for retina vascularization, cell type development, and layer lamination were determined and compared across species and developmental ages. Vascularization emerges and progresses over the investigated developmental timespan in both species. In parallel, lamination of nuclear layers progresses from two (ganglion cell layer = GCL vs. neuroblast layer = NBL) layers to the mature pattern of three layers (GCL-inner nuclear layer = INL-outer nuclear layer = ONL). Molecular markers of retinal cell types and markers of inner plexiform layer (IPL) lamination are appearing at the onset of the studied time points and progressively settle into the adult pattern of localization. A strong central-to-peripheral delay is observed in human retinas at GW18 and GW20. It therefore appears that human midgestation retina development is mirrored in the first 2 weeks of mouse postnatal development. The present work closes a gap in the literature concerning the correlation between human and mouse retinal maturation timelines. The stages identified and their anatomical landmarks may provide as a basis for future comparative studies.