Biomedical subjects
Publications and source records attributed to D S Minckler.
Two unrelated patients with thoracic-pelvic-phalangeal dystrophy syndrome had retinal degeneration. A pathologic study of both eyes from one of the patients showed severe degeneration of the peripheral retina, with predominantly cone-type cells remaining.
A 33-year-old woman with Hodgkin's disease developed a painless progressive loss of vision in both eyes. Despite an ophthalmoscopic appearance of white-yellow retinal necrosis and retinal hemorrhage similar to that described with Hodgkin's disease, no sign of the disorder was found at autopsy. Instead, widespread evidence of Herpesviridae family virus infection was present in several organs, including the retinas. Opportunistic infection, including herpes simplex and cytomegalovirus, should be considered when retinitis complicates Hodgkin's disease.
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In the primate, ganglion cells of the temporal retina project ipsilaterally and those of the nasal retina, contralaterally into the optic tract. The vertical meridian passing through the fovea defines the border between these two populations of ganglion cells and has been demonstrated in four Macaque monkeys after unilateral injection of horseradish peroxidase into the dorsal lateral geniculate nucleus and examination of the pattern of retrograde labeling of those ganglion cells projecting to the injected side. A median 1 degree vertical strip in which ipsi- and contralaterally projecting ganglion cells intermingle was found, confirming the report by Stone et al. ('73). In addition, occasional extrafoveal labeled ganglion cells were found as far as 2 degrees from the vertical midline in the otherwise unlabeled hemiretinae. These ganglion cells were not numerous and had somata of all sizes, suggesting that they do not constitute a separate class of ganglion cells as found in the temporal retina of the cat. In contrast to the description by Stone et al. ('73), the strip of vertical overlap did not show a constant width through the fovea, since mixing of labeled and unlabeled ganglion cells was found in a band approximately 1/2 degree wide along both the nasal and temporal rims of the foveal pit which is 500 mum (2 degrees) in diameter. Beyond these 1/2 degree arcs, the appropriate hemiretina was either completely unlabeled, or contained virtually every ganglion cell labeled on the side projecting to the injected dorsal lateral geniculate nucleus. The scattered labeled ganglion cells rimming an otherwise unlabeled hemifovea represent a possible anatomical basis for the phenomenon of "macular" or "foveal sparing" in which unilateral damage to the occipital cortex produces homonymous hemianopsia with sparing of a small island of centralmost vision extending about 1 degree from the foveal center. From this study, it is not possible to define the receptive fields or specific photoreceptor connections of the ganglion cells labeled with horseradish peroxidase, so that at the present time quantitative correlations cannot be made between the numbers of ganglion cells remaining on the affected side of the fovea and the extent of preservation of visual function in the spared zone. The presence of labeled ganglion cells rimming the fovea in its entirety is compatible with the sequence of foveal development in late prenatal life. After lateral displacement both nasally and temporally of ganglion cells which initially lay in the median vertical overlap strip of 1 degree, in the adult retina a strip approximately 1/2 degree wide around the perimeter of the foveola should contain a mixture of ipsi- and contralaterally projecting ganglion cells. The total population of ganglion cells beyond this 1/2 degree band should be completely ipsi- or contralateral in their projection patterns, as is observed...
A 74-year-old woman had a radical anterior segment resection for epithelial ingrowth following cataract extraction. Light microscopy demonstrated the presence of a sheet of cells morphologically similar to conjunctival epithelium covering the superior half of the inner surface of the cornea, iris, and ciliary processes. Electron microscopy revealed that frequent hemidesmosomes and a well-developed basal lamina were consistently present along the base of the ingrowing epithelium. The tissue immediately beneath the ingrowing epithelium, lining the cornea, trabecular meshwork and iris, morphologically resembled the subepithelial zone that has been described along the human skin epidermal-dermal junction. Additionally, focal areas of necrosis were noted in the trabecular meshwork. The major structural alterations induced on the surfaces of intraocular structures by the invading epithelium and the associated necrosis probably are responsible for the glaucoma which occurs with epithelial ingrowth.
Orthograde and retrograde axoplasmic transport were studied in optic nerve heads of seven hypotensive Macaca fascicularis eyes. Orthograde transport was studied by radioautography after intravitreal radioisotope injections. Retrograde transport was studied in the same eyes by horseradish peroxidase injection into the dorsal lateral geniculate nuclei or optic tracts. Three eyes had developed marked papilledema before injections. Orthograde axoplasmic transport was blocked in swollen axons of the optic disc anterior to Bruch membrane and in the lamina scleralis. Retrograde transport was blocked in axons within the lamina scleralis along the posterior edges of transverse scleral beams and in axons in the choroidal portion of the nerve head posterior to Bruch membrane. These results support the general concept that axoplasmic transport in the optic nerve head is sensitive to alterations in intraocular pressure, either increases or decreases. The edges of Bruch membrane and the openings in the lamina scleralis may constrict axon bundles in ocular hypotony.
The pattern of retinal ganglion cell projections to the dorsal lateral geniculate nuclei has been demonstrated with horseradish peroxidase neuronography. A 1 degree-wide strip centered on the vertical meridian has been found in which ipsilaterally and contralaterally projecting ganglion cells intermingle. This strip expands to a width of 3 degrees at the fovea, since mixing of horseradish peroxidase-labeled and unlabeled ganglion cells was found in a band approximately 0.5 degrees wide along both the nasal and temporal rims of the foveola. These labeled ganglion cells rimming the foveal pit in its entirety represent a possible anatomical basis for "foveal sparing".
Horseradish peroxidase has been injected into the dorsal lateral geniculate nucleus of macaque monkeys to label ganglion cells of the retina by retrograde axoplasmic transport. Displaced ganglion cells, with somata in the inner nuclear layer and dendrites in the inner plexiform layer, were detected by virtue of their filling with peroxidase-positive granules. These cells were numerous in the peripapillary region, but relatively uncommon elsewhere in the retina.
Orthograde and retrograde axoplasmic transport have been studied in the optic nerve heads of 37 Macaca fascicularis eyes with normal or elevated intraocular pressure (IOP) produced by cannulation of the anterior chamber. Orthograde transport was labeled by 3H-amino acids injected intravitreally and incorporated into retinal ganglion cell proteins. Retrograde transport was studied in the same eyes by injecting horseradish peroxidase (HRP) into one or both optic tracts and dorsal lateral geniculate nuclei (dLGN). Both tracers accumulated in the lamina scleralis (LS) of eyes maintained at pressures of 25 to 150 mm. Hg for 12 to 28 hours (pressure in normal controls = 10 to 14 mm. Hg) but the HRP technique was markedly more sensitive. The degree of retrograde transport obstruction in the LS appeared to be directly proportional to both the height and the duration of elevated IOP. In one experiment, the blockades of orthograde and retrograde transport induced at 50 mm. Hg were demonstrated to be reversible. Serial reconstructions of radioautographs and peroxidase-reacted sections of the optic nerve heads demonstrated that the orthograde and retrograde transport obstructions were coincidental anatomically by light microscopy in the LS and occurred most prominently in the temporal quadrants of the nerve head. These transport obstructions occurred at moderate elevations of IOP (25 TO 50 mm. Hg) despite (1) elevated arterial PO2 levels during inhalation of 100 percent oxygen and (2) intact nerve head capillary circulation, as demonstrated by perfusion with nucleated avian erythrocytes.
A previously healthy 44-year-old man died three weeks after the simultaneous onset of encephalitis and retinitis. Fundus changes were bilateral and included papillitis, rapidly progressive central retinal vein obstruction, and massive exudative retinal detachment. A 16-fold rise in herpesvirus hominis antibodies occured between the 10th and 20th days of illness. At autopsy, the brain showed changes characteristic of herpetic encephalitis, and cultures of the brain yielded Herpesvirus hominis type I. Intranuclear inclusion bodies typical of those produced by Herpesvirus were found by light microscopy in brain, optic nerves, retina, and choroid. Herpesvirus particles were found by electron microscopy in brain, optic nerve, and retina.
Cyclocryotherapy of the monkey eye reliably produces transient increased intraocular pressure followed by prolonged hypotony, during which papilledema occurs. Axoplasmic transport was studied while the intraocular pressure was both increased and decreased after cyclocryotherapy by autoradiography following the intravitreal injection of tritiated leucine and proline. Surgical fistulization of the anterior chamber was also used to produce hypotony and papilledema. Significant alterations of both the rapid and the slow components of axoplasmic transport were demonstrated in the nerve head during increased intraocular pressure, and in ocular hypotony with papilledema.
Quantitative measurements of the composition of axonal bundles were made from electron micrographs for six levels within the intraocular portion of the optic nerve head of the rhesus moneky. The proportion of the areas occupied by axonal cytoplasm, glial cytoplasm, mitochondria, and myelin was calculated. Average axonal diameters were determined at each location. Axonal bundles acquired progressively more interaxonal glial tissue as they passed posteriorly from the region of the optic disk toward the optic nerve. Mitochondria were present within axons in increased numbers in the lamina choroidalis and lamina scleralis, and there may be focal expansions and constrictions of axons in the same regions. The overall cross-sectional area of the intraocular portion of the optic nerve expanded posterior to Bruch's membrane in part because of the addition of the interaxonal glial tissue.
Cyclocryotherapy was a reliable method of producing prolonged decreased intraocular pressure and papilledema in the rhesus monkey. Histologic changes in papilledema caused by decreased pressure were indistinguishable from those in papilledema from increased intracranial pressure. Electron microscopic observations in papilledema after cyclocryotherapy suggested that the principal morphologic alteration in the optic disk is axonal swelling. Additionally, many mitochondria accumulated in some swollen axons. These changes, observed at the ultrastructural level, suggest that alternations of axoplasmic transport may play a significant role in the pathogenesis of swelling of the disk.
A systematic study of axoplasmic transport in the normal optic nerve head is essential to the understanding of the role of this process in the pathogenesis of disease of the optic nerve. Twenty-one eyes from normal adult rhesus monkeys were subjected to intravitreal injections of tritiated leucine (3H) or proline (3H). Light microscopic autoradiographs were prepared on these eyes and optic nerves six hours to 60 days after injection. The isotope that was incorporated in cytoplasmic components associated with the slow phase of axoplasmic transport (3H leucine) became concentrated in the temporal region of the optic nerve head, unevenly distributed within axons in the axonal bundles, and apparently accumulated in axons or glial cells, or both, in the lamina choroidalis and scleralis as a broad pulse of isotope moved across the optic nerve head. Several anatomic factors, including the distribution of macular fibers, increasing amounts of glial cells within the same axonal bundles as the optic nerve passed from the lamina retinalis to the lamina scleralis, and the abrupt addition of myelin sheaths to axons behind the lamina scleralis, contributed to the complex distribution of isotope in the normal optic nerve head. Glial cell labeling was especially prominent with 3H proline.