We have examined the morphology and distribution of neurones that contain nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase in human retinae. NADPH-diaphorase reactivity was observed in three different classes of amacrine cells (ND1, ND2, ND3 cells) and in the cone photoreceptors. ND1 cells had relatively large somata (mean, 12.3 ¼m) located in the inner nuclear layer (INL) and in the ganglion cell layer (GCL). Their dendrites were often strongly labeled and spread into either the middle or outer strata of the inner plexiform layer (IPL). The somata of ND2 cells were medium-sized (mean, 8.2 ¼m) and located in the INL and in the GCL; their dendrites were usually beaded and often spread in either the middle or outer strata of the IPL. ND3 cells had small, round somata (mean, 5.2 ¼m) located in either the INL or GCL, and were without labeled processes. The total number of NADPH-diaphorase cells (all classes) was estimated at 118,000, with a mean density of about 100/mm2. The most striking fea ture of NADPH-diaphorase cells in humans was that their distribution was relatively uniform across the retina, with no evidence of a peak in density at the foveal rim.

Cones in the foveola of adult primate retina are narrower and more elongated than cones on the foveal rim, which in turn, are narrower and more elongated than those located more eccentric. This gradient of cone morphology is directly correlated with cone density and acuity. Here we investigate the hypothesis that fibroblast growth factor (FGF) signaling mediates the morphological differentiation of foveal cones—in particular, the mechanism regulating the elongation of foveal cones. We used immunoreactivity to FGF receptor (R) 4, and quantitative analysis to study cone elongation on the horizontal meridian of macaque retinae, aged between foetal day (Fd) 95 and 2.5 years postnatal (P 2.5y). We also used in situ hybridization and immunohistochemistry to investigate the expression patterns of FGF2 and FGFR1–4 at the developing fovea, and three other sample locations on the horizontal meridian. Labeled RNA was detected using the fluorescent marker “Fast Red” (Roche) and levels of expression in cone inner segments and in the ganglion cell layer (GCL) were compared using confocal microscopy, optical densitometry, and tested for statistical significance. Our results show that morphological differentiation of cones begins near the optic disc around Fd 95, progressing toward the developing fovea up until birth, approximately. Levels of FGF2 and FGFR4 mRNAs expression are low in foveal cones, compared with cones closer to the optic disc, during this period. There is no similar gradient of FGF2 mRNA expression in the ganglion cell layer of the same sections. Maturation of foveal cones is delayed until the postnatal period. The results suggest that a wave of cone differentiation spreads from the disc region toward the developing fovea during the second half of gestation in the macaque. A gradient of expression of FGFR4 and FGF2 associated with the wave of differentiation suggests that FGF signalling mediates cone narrowing and elongation.

Most primate retinas have an area dedicated for high visual acuity called the fovea centralis. Little is known about specific mechanisms that drive development of this complex central retinal specialization. The primate area of high acuity (AHA) is characterized by the presence of a pit that displaces the inner retinal layers. Virtual engineering models were analyzed with finite element analysis (FEA) to identify mechanical mechanisms potentially critical for pit formation. Our hypothesis is that the pit emerges within the AHA because it contains an avascular zone (AZ). The absence of blood vessels makes the tissue within the AZ more elastic and malleable than the surrounding vascularized retina. Models evaluated the contribution to pit formation of varying elasticity ratios between the AZ and surrounding retina, AZ shape, and width. The separate and interactive effects of two mechanical variables, intraocular pressure (IOP) and ocular growth-induced retinal stretch, on pit formation were also evaluated. Either stretch or IOP alone produced a pit when applied to a FEA model having a highly elastic AZ surrounded by a less elastic region. Pit depth and width increased when the elasticity ratio increased, but a pit could not be generated in models lacking differential elasticity. IOP alone produced a deeper pit than did stretch alone and the deepest pit resulted from the combined effects of IOP and stretch. These models predict that the pit in the AHA is formed because an absence of vasculature makes the inner retinal tissue of the AZ very deformable. Once a differential elasticity gradient is established, pit formation can be driven by either IOP or ocular growth-induced retinal stretch.