Development of Retinal Layers in Prenatal Human Retina

Abstract

Purpose: To determine the developmental sequence of retinal layers to provide information on where in utero pathologic events might affect retinal development.

Design: Qualitative and quantitative descriptive research.

Methods: A histology collection of human eyes from fetal week (Fwk) 8 to postnatal (P) 10 weeks was analyzed. The length of the nasal and temporal retina was measured along the horizontal meridian in 20 eyes. The location of the inner plexiform layer (IPL) and outer plexiform layer (OPL) was identified at each age, and its length measured.

Results: The human eye retinal length increased from 5.19 mm at Fwk 8 to 20.92 mm at midgestation to 32.88 mm just after birth. The IPL appeared in the presumptive fovea at Fwk 8, reached the eccentricity of the optic nerve by Fwk 12, and was present to both nasal and temporal peripheral edges by Fwk 18-21. By contrast, the OPL developed slowly. A short OPL was first present in the Fwk 11 fovea and did not reach the eccentricity of the optic nerve until midgestation. The OPL reached the retinal edges by Fwk 30. Laminar development of both IPL and OPL occurred before vascular formation.

Conclusions: In human fetal retina, the IPL reached the far peripheral edge of the retina by midgestation and the OPL by late gestation. Only very early in utero events could affect IPL lamination in the central retina, but events occurring after Fwk 20 in the peripheral retina would overlap OPL laminar development in outer retina.

FIGURE 1

Section through the horizontal meridian of a fetal week (Fwk) 12 human eye. The cornea (C), lens (L), optic nerve (ON), and fovea are indicated. The peripheral edge of the retina, called “edge” in the text, is marked with arrows.

FIGURE 2

Growth of the prenatal human eye. (Left) Gross measurements of axial length and diameter of human eyes from fetal week (Fwk) 7–27. (Right) Schematic drawings showing the elongation of the human horizontal meridian from Fwk 8 (innermost) to postnatal 1 week (outermost). The eyes are aligned on the optic nerve (ON). The asterisks mark the bulge in which the fovea develops. The arrowheads indicate the proximal and distal edge of the nasal pars plana; note its increase in length between Fwk 17 and birth.

FIGURE 3

Development of the inner plexiform layer in the human retina. (Left) Fetal week (Fwk) 8 future foveal region showing a narrow inner plexiform layer (IPL) and a thick ganglion cell layer (GCL). Although there are no layers in the outer neuroblastic layer (ONbL), cones (c) can be identified. (Middle) Fwk 8 nasal retina near the optic nerve (ON). Ganglion cell axons (GCL) form a narrow nerve fiber layer (NFL) on the temporal side of the ON. No IPL is present. Mitotic figures (M) are present at the retinal outer surface. (Right) The midperipheral retina at Fwk 15 showing a distinct thick IPL separating the GCL and the thick ONbL. The outer plexiform layer is not yet present, and mitotic figures (M) are numerous at the outer surface. Scale bar in Middle for all.

FIGURE 4

Development of the outer plexiform layer (OPL) in the human retina. (Top right) The fetal week (Fwk) 10.7 fovea is the earliest age that all 5 layers are present. Note the single layer of cones (c) and the thin OPL compared to the thick inner plexiform layer (IPL). (Top middle) Fwk 21 retina temporal to the optic nerve (ON); this region now contains 5 mature layers. (Top right) The developing OPL in the Fwk 25 peripheral retina. The first step involves a gap appearing in the thick outer retina (arrow), dividing it into outer nuclear (ONL) and inner nuclear (INL) layers. Compare the immature OPL with the well-developed IPL at this point. Scale bar in Top right for Top left, middle, and right. (Bottom) Far temporal retina at Fwk 35 with edge of the retina and the pars plana (PP) to the left. The advancing blood vessel front (BV) has not yet reached the retinal edge. All layers are complete close to the edge with an unlaminated region (double arrows) near the PP; this persists until after birth.