Abstract
Abstract: :
Purpose: Factors affecting centrifugal and centripetal cell movements at the developing primate fovea remain to be explained. In this study we evaluated the role of intraocular pressure (IOP) and retinal stretch due to eye growth on foveal pit formation. Pit formation begins in the highly elastic foveal avascular zone (FAZ). Retinal sections from early fetal to adult Macaca nemestrina monkeys were used to quantify how retinal tissue is affected by pressure and stretch. Methods: Finite element analysis (FEA) models having a FAZ flanked by a less elastic perifovea had pressure applied to one surface and were stretched simultaneously. Measurements of retinal thickness, foveal pit depth and width were made in paraffin sections through macaque retinas varying in age from fetal day 73 to 12 years. Results: The FEA models showed that intraocular pressure or stretch were each able to create a pit, accounting for the centrifugal movement of inner retinal cells. However, pit depth was greatest when both variables were applied. Anatomical thickness measurements of the three cellular laminae indicated that the peripheral nasal and temporal retina thinned with age, but the central retina around the fovea did not. Analysis of the developing pit indicated that the thinning inner nuclear layer (INL) overlying the pit was deflected outward, suggesting that IOP was operating in the formation of the fovea. This outward bending of the INL was flattened out with age, suggesting that retinal stretch operated after the pit reached its maximal depth. Other evidence that IOP affects retinal morphology was provided by the progressive thinning of the INL and outer plexiform layers overlying arteries in the ganglion cell layer to form outwardly bending micropits. These micropits resembled the morphology of the developing fovea. Conclusions: We have modified our mechanical model of fovea formation to incorporate the role of IOP. IOP and stretch applied to the highly elastic FAZ initially cause the pit to form. A second phase begins after the pit has reached maximal depth in which eye growth induces retinal stretch. Retinal stretching creates bending around the pit, causing the tissue at the pit to lift inwardly, thereby pulling the cones centripetally and flattening the floor of the pit. This model predicts that a significant amount of pit formation must occur before cone density begins to increase. Available quantitative data in both macaques and marmosets support this sequence of events, further validating the model. Supported by NIH EY-04536 (AH) and Kayser Award (AH).
Keywords: retinal development • macula/fovea • anatomy