PubMed HealthSearch

Biomedical subjects

R A Schumer

Publications and source records attributed to R A Schumer.

11 recordsLinked to original sources

Elevated glutamate levels in the vitreous body of humans and monkeys with glaucoma.

OBJECTIVE: To explore the possibility that the excitatory amino acid glutamate might be associated with the disease process of glaucoma, which is characterized by the death of retinal ganglion cell neurons and subsequent visual dysfunction. METHODS: Amino acid analyses were performed on vitreous specimens that were obtained from patients who were undergoing cataract extraction. Samples were collected prospectively from those patients who sustained inadvertent rupture of the posterior capsule between 1988 and 1993. An additional set of specimens, obtained from both eyes of monkeys, was analyzed; in these monkeys, glaucoma had been experimentally induced in one eye only. RESULTS: A twofold elevation in the level of glutamate was detected in the vitreous body of the group of patients with glaucoma when compared with that in a control population of patients with cataracts only. An even greater elevation of the glutamate level was found in the vitreous body of glaucomatous eyes of monkeys when compared with that in control eyes. No statistical differences were detected among other amino acid levels from the vitreous body of glaucomatous and nonglaucomatous eyes in humans or monkeys. CONCLUSIONS: The excitatory amino acid glutamate is found in the vitreous body of glaucomatous eyes at concentrations that are potentially toxic to retinal ganglion cells. The increased level of this known neurotoxin is consistent with an "excitotoxic" mechanism for the retinal ganglion cell and optic nerve damage in glaucoma. Therapies to protect neurons against glutamate toxic effects may prove to be useful in the management of this blinding disease.

Aged

Differential vulnerability of neurochemically identified subpopulations of retinal neurons in a monkey model of glaucoma.

The vulnerability of subpopulations of retinal neurons delineated by their content of cytoskeletal or calcium-binding proteins was evaluated in the retinas of cynomolgus monkeys in which glaucoma was produced with an argon laser. We quantitatively compared the number of neurons containing either neurofilament (NF) protein, parvalbumin, calbindin or calretinin immunoreactivity in central and peripheral portions of the nasal and temporal quadrants of the retina from glaucomatous and fellow non-glaucomatous eyes. There was no significant difference between the proportion of amacrine, horizontal and bipolar cells labeled with antibodies to the calcium-binding proteins comparing the two eyes. NF triplet immunoreactivity was present in a subpopulation of retinal ganglion cells, many of which, but not all, likely correspond to large ganglion cells that subserve the magnocellular visual pathway. Loss of NF protein-containing retinal ganglion cells was widespread throughout the central (59-77% loss) and peripheral (96-97%) nasal and temporal quadrants and was associated with the loss of NF-immunoreactive optic nerve fibers in the glaucomatous eyes. Comparison of counts of NF-immunoreactive neurons with total cell loss evaluated by Nissl staining indicated that NF protein-immunoreactive cells represent a large proportion of the cells that degenerate in the glaucomatous eyes, particularly in the peripheral regions of the retina. Such data may be useful in determining the cellular basis for sensitivity to this pathologic process and may also be helpful in the design of diagnostic tests that may be sensitive to the loss of the subset of NF-immunoreactive ganglion cells.

Animals

A scleral tunnel incision for trabeculectomy.

PURPOSE: We used a modified technique to construct the trabeculectomy flap. METHODS: The technique involved the creation of a scleral tunnel as is used in phacoemulsification surgery for cataract. RESULTS: We have used this technique in our most recent 90 cases. We believe it is an easier technique to perform than conventional flap dissection, and that it yields improved flap construction. CONCLUSIONS: The scleral tunnel flap technique offers a number of advantages over standard flap construction in trabeculectomy surgery.

Glaucoma

Microbial contamination of medications used to treat glaucoma.

AIMS: A study was conducted to estimate the frequency of contamination of topical antiglaucoma medications used by asymptomatic patients. METHODS: The drops and the bottle tips of 194 in use topical medications and the conjunctiva from 109 treated glaucoma patients were cultured. RESULTS: Bacteria were recovered from 55 (28%) medications. The bottle tip was more frequently contaminated than the drops (p = 0.008). Gram positive organisms were cultured from 50 (91%) of 55 contaminated medications. Thirteen patients (12%) had the same microorganism recovered from the conjunctiva and from the contaminated medication. The frequency of contamination of medications increased with increasing duration of use. Bacterial contamination occurred in 19% of eyedrops less than 8 weeks old in contrast with 40% of bottles used for more than 8 weeks. CONCLUSION: Our data suggest that ocular medications to treat glaucoma frequently become contaminated with bacteria and that contamination is related to duration of use. We therefore recommend that opened topical antiglaucoma eyedrops should be replaced on a regular basis.

Aged

The nerve of glaucoma!

Contemporary concepts of open angle glaucoma suggest that the current emphasis on reduction of elevated intraocular pressure could be augmented by other therapeutic approaches. In this article, we describe significant recent developments in the molecular and cellular biology and neuropharmacology of nerve damage that are likely, in coming years, to suggest new therapeutic approaches to the management of glaucoma. These developments may lead to the achievement of pharmacologic protection of the optic nerve from damage or possibly promotion of reversal of damage. We review selected studies of excitotoxins and N-methyl-D-aspartate receptor antagonists, Ca(2+)-induced damage and calcium channel blockers, the intracellular messenger nitric oxide and its perturbation, free-radical damage and scavengers, nerve regeneration, and growth factors. Several basic research questions are posed, answers to which may transform our concepts of glaucoma therapy.

Animals

Intraocular pressure reduction with PhXA34, a new prostaglandin analogue, in patients with ocular hypertension.

In a randomized, double-masked, parallel study, one drop of 0.003% (1 microgram; n = 9) or 0.01% (3 micrograms; n = 10) PhXA34, a new phenyl-substituted prostaglandin F2 alpha analogue (13,14-dihydro-15[R,S]-17-phenyl-18,19,20-trinor-prostaglandin F2 alpha-1-isopropyl ester), or its vehicle (n = 10) was applied topically twice daily for 6 days to one eye in each of 29 patients with ocular hypertension. Compared with either baseline, contralateral, or vehicle control values, PhXA34 caused a significant (P < .001) dose-dependent reduction of intraocular pressure. The reduction lasted at least 12 hours after each drop and 24 to 48 hours after the last drop, with a significant (P < .0001) mean +/- SEM reduction of as much as 10 +/- 1 mm Hg (40%). Conjunctival hyperemia was not produced by 0.003% PhXA34, but was noted in some eyes treated with 0.01% PhXA34, and after repeated tonometry with either concentration. The prostaglandin analogue did not produce clinically obvious miosis, anterior chamber flare or cellular response, or any subjective adverse effects. PhXA34 is a potent, effective, and well-tolerated ocular hypotensive agent based on our results in this small, short-term study. Its potential as a new drug for glaucoma therapy warrants further investigation in long-term, larger studies.

Adult

Selectivity for orientation and direction of motion of single neurons in cat striate and extrastriate visual cortex.

1. We consider the consequences of the orientation selectivity shown by most cortical neurons for the nature of the signals they can convey about the direction of stimulus movement. On theoretical grounds we distinguish component direction selectivity, in which cells are selective for the direction of movement of oriented components of a complex stimulus, from pattern direction selectivity, or selectivity for the overall direction of movement of a pattern irrespective of the directions of its components. We employed a novel test using grating and plaid targets to distinguish these forms of direction selectivity. 2. We studied the responses of 280 cells from the striate cortex and 107 cells from the lateral suprasylvian cortex (LS) to single sinusoidal gratings to determine their orientation preference and directional selectivity. We tested 73 of these with sinusoidal plaids, composed of two sinusoidal gratings at different orientations, to study the organization of the directional mechanisms within the receptive field. 3. When tested with single gratings, the directional tuning of 277 oriented cells in area 17 had a mean half width of 20.6 degrees, a mode near 13 degrees, and a range of 3.8-58 degrees. Simple cells were slightly more narrowly tuned than complex cells. The selectivity of LS neurons for the direction of moving gratings is not markedly different from that of neurons in area 17. The mean direction half width was 20.7 degrees. 4. We evaluated the directional selectivity of these neurons by comparing responses to stimuli moved in the optimal direction with those elicited by a stimulus moving in the opposite direction. In area 17 about two-thirds of the neurons responded less than half as well to the non-preferred direction as to the preferred direction; two-fifths of the units responded less than one-fifth as well. Complex cells showed a somewhat greater tendency to directional bias than simple cells. LS neurons tended to have stronger directional asymmetries in their response to moving gratings: 83% of LS neurons showed a significant directional asymmetry. 5. Neurons in both areas responded independently to each component of the plaid. Thus cells giving single-lobed directional-tuning curves to gratings showed bilobed plaid tuning curves, with each lobe corresponding to movement in an effective direction by one of the two component gratings within the plaid. The two best directions for the plaids were those at which one or other single grating would have produced an optimal response when presented alone.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Abolition of visual cortical direction selectivity affects visual behavior in cats.

We reared cats in an environment illuminated stroboscopically at 8 Hz, and studied their ability to detect and discriminate the direction of motion of sinusoidal gratings. Normal cats, like humans, could discriminate the direction of a grating's motion at contrasts that are just barely visible. Strobe-reared cats could detect the grating at contrasts similar to those required by normal cats, but required contrasts that were about 10 times threshold to identify the direction of motion. We subsequently studied the activity of single units in the striate cortex in these cats, and found that directional motion selectivity--normally a prominent feature of striate cortical neurons--was almost absent; other cortical receptive field properties were roughly normal. These results suggest that directionally selective neurons are involved in visual discriminations based on the direction of motion.

Animals

Binocular disparity modulation sensitivity to disparities offset from the plane of fixation.

Corrugated disparity gratings mounted on depth pedestals were portrayed with random-dot stereograms in order to measure the cyclopean disparity modulation transfer function at various offsets from fixation. We found changes in both sensitivity as well as shape as the magnitude of the pedestal varied. Threshold disparity modulation amplitude curves, plotted as a function of corrugation frequency, became narrower and shifted toward lower frequencies as pedestal size increased. There were stable asymmetries between sensitivities to crossed and uncrossed pedestals; these could be accounted for by assuming each observer to have a constant fixation disparity on the order of 5' of arc.

Depth Perception

Length summation in simple cells of cat striate cortex.

We have examined two models for the preference displayed by cortical simple cells for elongated stimuli having a particular orientation. Both assume that geniculate afferents with aligned receptive fields pool to form the receptive field of the cortical unit. The first model [Marr and Hildreth, Proc. R. Soc. Lond. Ser. B 200, 269-294 (1980)], includes AND gating along the length axis so that a simple cell does not fire unless a critical number of its afferents with adjacent receptive fields are firing. The second model assumes that geniculate input is simply summed over subunits and then passed through a firing threshold. Both models account for the unresponsiveness of simple cells to spots of light, but the AND model predicts a discontinuous length threshold, while the summation model predicts that length and contrast should be interchangeable in the determination of the response threshold. Experiments in which length and contrast were systematically varied support the summation model, and extend the notion of linear spatial summation to the length axis in simple cells.

Animals