Purpose:
To understand the mechanisms underlying inner retinal cell translocations as the primate fovea forms, the changing shapes of the ganglion cell (GCL) and inner nuclear (INL) layers were evaluated over development.
Methods:
Measurements were made in paraffin sections through macaque retinas varying in age from 95-180 days postconception (dpc). Tracings of foveal sections were used to create finite element analysis (FEA) models comprising the 3 nuclear and 2 plexiform laminae. Artifactual histological deformations within the model were eliminated with a FEA dewarping procedure that had a negligible distorting effect on FEA model area (-0.15%). After dewarping, the GCL and INL laminae were extracted from the FEA models and were evaluated with regard to how they changed as the pit formed.
Results:
If cells were actively moving from the center of the nascent fovea, they would not be expected to move outwardly as they moved tangentially. A pit was not present at 95 dpc. Progressive tangential displacement of central GCL and INL cells was observed between 150-180 dpc. In addition, at 150 dpc, the GCL was outwardly displaced by 30 µm, but the INL was not outwardly displaced. At 164 dpc, both the GCL and INL were displaced outwardly by 65 and 27 µm, respectively. At 180 dpc, the outward displacement of the GCL increased to 77 µm, while the INL was displaced outwardly by only 22 µm. An FEA model simulating the effect of intraocular pressure (IOP) on the inner surface of a developing retina having an avascular zone (Fig. 1A) produced bi-directional, tangential and outward, laminar displacements (Fig. 1B) that were effectively identical to those seen in vivo as the pit forms.
Conclusions:
As the pit forms, inner retinal cells are displaced bi-directionally. The differential tangential and outward displacements of the GCL and INL generate a pit with sloping walls. The GCL is displaced outwardly more that the INL and this result is consistent with IOP forces acting on the inner retinal surface. The analyses support the hypothesis that the pit and its shape form as a result of passive, mechanical displacement of avascular inner retinal tissue by IOP onset, rather than by active cellular movements.
Keywords: macula/fovea • development • retina