Fig 1.
Diagram comparing eye anatomy of the adult human and neonatal mouse.
The outer retinal layers are supplied by blood vessels (BV1) from the posterior ciliary arteries, terminating in the choriocapillaris, a fenestrated capillary network without tight junctions. An outer blood-retinal barrier is formed by tight junctions in the retinal pigment epithelial cells, after which oxygen is supplied by diffusion to the outer retina. An inner blood-retinal barrier is formed by adult capillary endothelial cells with tight junctions (BV2, filled walls) originating from the central retinal artery. The optic nerve head is supplied primarily by a vascular circle (BV3) from the posterior ciliary arteries, and from the peripapillary choroid vessels. The body of the optic nerve is supplied from the ophthalmic artery via the pial plexus of blood vessels which penetrate the nerve (BV4). The endothelial cells of adult optic nerve capillaries have tight junctions, forming a blood-optic nerve barrier. Capillaries of the inner retina, and possibly the optic nerve, have limited blood-retina and blood-optic nerve barriers (unfilled walls) in the late fetal mouse.
Fig 2.
Skin (S) covers the eye of the neonatal mouse. The ganglion cell layer (GCL) and neuroblast layer (NBL) of the retina are separated by a pale inner plexiform layer (for more detail see Fig 3). The optic nerve (ON) is seen at the lower right of the image (for more detail see Fig 5). The retinal pigment epithelium (arrow) is separated from the rest of the retina by an artefactual space (A). C: Cornea, L: lens. AMG/hematoxylin, Bar = 100 μm.
Fig 3.
Ganglion cells in the ganglion cell layer (GCL) are numerous in the neonatal mouse, and the nerve fibre layer (NFL) is prominent. Involuting hyaloid vessels (asterisk) are seen on the surface of the retina. The future inner nuclear layer (INL) is three-to-four cells thick below the inner plexiform layer (IPL), with slightly paler nuclei (best seen in Fig 4B) than the underlying neuroblast layer (NBL), the source of the photoreceptors. At this magnification black AMG grains are just visible in the ganglion cell layer (see Fig 4A for a high power view). AMG/hematoxylin, Bar = 20 μm.
Fig 4.
A. AMG grains are attached to the nuclear membranes of scattered ganglion cells (eg, arrowheads in inset) and in endothelial cells (open arrow). A few AMG grains are present in the inner plexiform layer, and in nuclear membranes (eg, closed arrow) and endothelial cells of the inner nuclear layer. A mitosis (asterisk) is present in the nerve fibre layer. B. No AMG grains are seen in the cells of the inner retina in a neonatal mouse that had not been exposed to prenatal mercury vapor. NFL: nerve fibre layer, GCL: ganglion cell layer, IPL: inner plexiform layer, INL: inner nuclear layer, NBL: neuroblast layer. AMG/hematoxylin, Bars = 20 μm.
Fig 5.
Mercury in the retinal pigment epithelium and optic nerve head.
In a mouse exposed to mercury vapor, two nerve fibre bundles (open arrows) descend from the retinal nerve fibre layer into the optic nerve (ON) head. Black AMG grains can be seen in the retinal pigment epithelium (closed arrows) adjacent to the optic nerve head (see Fig 6A for high power view), and within the optic nerve head itself (see Fig 6B for high power view). Remnants of hyaloid blood vessels are present (asterisks). NBL: neuroblast layer. AMG/hematoxylin, Bar = 20 μm.
Fig 6.
Mercury in the peripapillary retinal pigment epithelium and optic nerve head.
A. Numerous AMG grains (closed arrows) are present in the peripapillary posterior retinal pigment epithelium (Post RPE), with decreasing amounts of mercury in the epithelium as the distance from the optic nerve (ON) head increases. AMG grains are seen in a capillary at the edge of the optic nerve (open arrow) and within the optic nerve head itself. Inset: no AMG grains are seen in the anterior retinal pigment epithelium (Ant RPE) of the same mouse (see Fig 2 for location). B. In the optic nerve head, AMG grains are attached to glial cell nuclear membranes (eg, arrowheads in the inset), glial cell processes (eg, closed arrow), and endothelial cells (eg, open arrow). AMG/hematoxylin, Bars = 10 μm.
Fig 7.
Mercury in the intra-orbital and intracranial optic nerves.
A. The intra-orbital optic nerve (oON, dotted oval on left, box is at high power in panel B below) from one eye, and the intracranial optic nerve (cON, dotted oval on right) from the other eye, are present. The intracranial meningeal cells (open arrow) contain AMG grains. AMG/hematoxylin, Bar = 200 μm. B. The intraorbital optic nerve contains numerous AMG grains, both in glial nuclear membranes (eg, arrowheads in inset) and in processes. AMG grains are prominent in endothelial cells of the peripheral pial plexus (all open arrows) and their branches (closed arrow in inset) that penetrate the optic nerve. AMG/hematoxylin, Bar = 20 μm.
Fig 8.
Mercury in brain endothelial cells.
AMG grains are present in the endothelial cells (arrow) of a capillary within the thalamus. An occasional AMG grain is attached to an endothelial nuclear membrane (arrowhead). Surrounding neurons and glia do not contain mercury. AMG/hematoxylin, Bar = 10 μm.
Table 1.
Disorders with damage to the retina and optic nerve, compared to fetal uptake of mercury.