The optic nerve lamina region is a neural progenitor cell niche.

Retinal ganglion cell axons forming the optic nerve (ON) emerge unmyelinated from the eye and become myelinated after passage through the optic nerve lamina region (ONLR), a transitional area containing a vascular plexus. The ONLR has a number of unusual characteristics: it inhibits intraocular myelination, enables postnatal ON myelination of growing axons, modulates the fluid pressure differences between eye and brain, and is the primary lesion site in the age-related disease open angle glaucoma (OAG). We demonstrate that the human and rodent ONLR possesses a mitotically active, age-depletable neural progenitor cell (NPC) niche, with unique characteristics and culture requirements. These NPCs generate both forms of macroglia: astrocytes and oligodendrocytes, and can form neurospheres in culture. Using reporter mice with SOX2-driven, inducible gene expression, we show that ONLR-NPCs generate macroglial cells for the anterior ON. Early ONLR-NPC loss results in regional dysfunction and hypomyelination. In adulthood, ONLR-NPCs may enable glial replacement and remyelination. ONLR-NPC depletion may help explain why ON diseases such as OAG progress in severity during aging.

Recurrent endogenous candidal endophthalmitis in a premature infant.

Endogenous Candida endophthalmitis resulting from candidemia in low-birth-weight infants usually occurs as a retinochoroiditis, which is effectively treated with systemic antifungal agents. We report a case of Candida endophthalmitis that recurred 4 months after completion of systemic antifungal therapy. The recurrent Candida infection affected primarily the iris and lens, rather than the retina and choroid. Vitrectomy was required for diagnosis and treatment.

Intrinsic programs of patterned cell lineages in isolated vertebrate CNS ventricular zone cells.

Using long-term, time-lapse video-microscopy, we investigated how single progenitor cells isolated from the early embryonic cerebral cortex produce neurons and glia over time. Clones of 10 cells or less were produced by short symmetric or asymmetric division patterns, commonly terminating in a 'pair progenitor' for two morphologically identical neurons. Larger trees were composites of these short sub-lineages: more prolific neuroblasts underwent repeated asymmetric divisions, each producing a minor neuroblast that typically made (3/4)10 progeny, and a sister cell capable of generating more progeny. Particular division patterns were seen repeatedly. In contrast, glioblasts underwent a prolonged series of symmetric divisions. These patterned lineage trees were generated from isolated cells growing on plastic, suggesting they are largely intrinsically programmed. Our data demonstrate for the first time that CNS progenitor cells have stereotyped division patterns, and suggest that as in invertebrates, these may play a role in neural development.

Orbital barotrauma.

A 24-year-old man sustained orbital and facial injury when an industrial suction device attached to his face. Hemorrhage and edema within the orbital soft tissues were clinically evidenced by proptosis and restricted ocular motility and confirmed by computed tomography. No retinal hemorrhages or exudates were noted. Orbital soft tissue injury caused by sudden extreme decrease in extravascular atmospheric pressure (i.e., orbital barotrauma) is not well described in the ophthalmic literature. The findings in our case are remarkably similar to those seen with traumatic asphyxia and the ophthalmological hydrostatic pressure syndrome, two conditions attributed to an increase in intravascular pressure. Physiologically, our case and these conditions share a similar increase in transmural pressure at the capillary level that is responsible for fluid transudate and hemorrhage in the orbital soft tissues. Intraretinal hemorrhages and exudates typical of Purtscher's retinopathy were conspicuously absent in our patient.

Evaluating the visual field effects of blepharoptosis using automated static perimetry.

BACKGROUND: Quantitation of the effects of blepharoptosis on the visual field has largely been limited to manual kinetic perimetry using a single peripheral isopter. The authors evaluated the visual dysfunction caused by blepharoptosis using automated static full-threshold perimetry. METHODS: A custom static full-threshold 60 degrees test strategy on the Humphrey field analyzer was used to assess the visual fields of 20 volunteers at their normal baseline and after inducing mild and moderately severe blepharoptosis by applying gold weights to the eyelids. Threshold sensitivities were measured at points along the eight principal meridians, separated by 45 degrees, traditionally used to assess visual field impairment. RESULTS: For mild blepharoptosis, essentially all test points along the superior meridian were significantly depressed (P < 0.01), with an increase in slope secondary to greater decreases in sensitivity at more eccentric points. For moderately severe blepharoptosis, depression of the superior meridian was expectedly greater than that seen with mild blepharoptosis. Additionally, depression of the horizontal meridians and to a lesser extent the lower meridians also was noted. CONCLUSIONS: These results suggest that even mild blepharoptosis may be associated with depression of the superior visual field extending close to fixation. Ophthalmologists should be aware of the effect of blepharoptosis when testing for other ophthalmic or neurologic disorders using automated static perimetry. Full-threshold static perimetry can be used to quantitate the visual field loss associated with blepharoptosis as a means of evaluating visual impairment.

Divalent cations directly affect the conductance of excised patches of rod photoreceptor membrane.

Phototransduction in rod cells is likely to involve an intracellular messenger system that links the absorption of light by rhodopsin to a change in membrane conductance. The direct effect of guanosine 3',5'-monophosphate (cGMP) on excised patches of rod outer segment membrane strongly supports a role for cGMP as an intracellular messenger in phototransduction. It is reported here that magnesium and calcium directly affect the conductance of excised patches of rod membrane in the absence of cGMP and that magnesium, applied to intact rod cells, blocks a component of the cellular light response. The divalent cation-suppressed conductance in excised patches showed outward rectification and cation-selective permeability resembling those of the light-suppressed conductance measured from the intact rod cell. The divalent cation-suppressed conductance was partly blocked by a concentration of the pharmacological agent L-cis-diltiazem that blocked all of the cGMP-activated conductance. Divalent cations may act, together with cGMP, as an intracellular messenger system that mediates the light response of the rod photoreceptor cell.

Control of the light-regulated current in rod photoreceptors by cyclic GMP, calcium, and l-cis-diltiazem.

The effect of calcium ions on the cGMP-activated current of outer segment membrane was examined by the excised-patch technique. Changes in the extracellular calcium concentration had marked effects on the cGMP-activated current, while changes in intracellular calcium concentration were ineffective. Changes in calcium concentration in the absence of cGMP had little, if any, effect on membrane conductance. These results suggest that both intracellular cGMP and extracellular calcium can directly affect the conductance underlying the light response in rod cells. The pharmacological agent l-cis-diltiazem reversibly inhibited the cGMP-activated current when applied to the intracellular side of an excised patch. When superfused over intact rod cells, l-cis-diltiazem reversibly blocked much of the normal light response. The isomer, d-cis-diltiazem, did not significantly affect either patches or intact rod cells. Thus, the light-regulated conductance has binding sites for both calcium and cGMP that may interact during the normal light response in rod cells and a site specific for l-cis-diltiazem that can be used to identify and further study the conductance mechanism.

Internal dialysis of Limulus ventral photoreceptors.

The internal dialysis technique has been applied to Limulus ventral photoreceptors. This method potentially allows quantitative control of the concentration of diffusible molecules within living cells. During dialysis, Limulus photoreceptors retained their ability to respond to light. Under conditions of dim illumination, responses were normal for close to an hour. In bright light, abnormalities developed more rapidly. The reversible effects of raising the dialysate Mg2+ concentration and the entrance of rhodamine-labeled albumin into cells shows that the dialysis method is useful for assaying the effects of small or large molecules on visual transduction. This method has been used to examine the effects of nucleotide triphosphates and cyclic nucleotides. The results show that nucleotide triphosphates (5-10 mM) are required to maintain a low rate of spontaneous quantum bumps. The importance of cyclic nucleotides in transduction is less clear; the light response was reduced by either cGMP or cAMP but only at very high concentrations (10 mM).

Gap junctional conductance: comparison of sensitivities to H and Ca ions.

One cytoplasmic aspect of the junctional membrane between coupled pairs of Fundulus blastomeres was perfused with solutions of known H and Ca ion concentrations. Conductance of junctional membrane was decreased by either ion. The sensitivity to H ions was about 10,000 times greater than that to Ca ions. The results suggest that junctional conductance can be modulated by changes in H ion concentration near physiological pH, but that unphysiologically high concentrations of Ca ion, such as would be reached only on cell death, are required for comparable changes in junctional conductance.