Biomedical subjects
Publications and source records attributed to R L Purple.
A 28-year-old woman with Scheie syndrome (MPS I-S) presented with the unusual feature of extremely dense peripheral corneal clouding, allowing maintenance of good central visual acuity. Characteristic systemic features, an abnormal electroretinogram result, and absent alpha-L-iduronidase activity confirmed the diagnosis despite the unusual corneal pattern of clouding.
Increased intraocular pressure and vascular ligation models are often used in studies of global ocular ischemia. The purpose of this study is to perform a paired comparison of retinal recovery in these paradigms. Our data indicate that ERG b-wave recovery profiles, following identical periods of ischemia, differ significantly between models. We propose that increased intraocular pressure models induce greater retinal injury than vascular ligation models. We suggest that pressure or another aspect of the increased intraocular pressure model induces injury beyond that caused by ischemia alone and caution against direct comparison of results obtained using these two models.
PURPOSE: Although toxic to the retina in its native form, the iron chelator deferoxamine (DFO) shows no apparent retinal toxicity when bound to hydroxyethyl-starch (HES). Conjugation of DFO does not alter its iron binding properties. Once bound, iron is no longer active in the production of toxic oxygen intermediates. This investigation seeks to determine whether HES-conjugated DFO (HES-DFO) protects against ischemia-reperfusion injury in the retina. METHODS: Retinal ischemia was induced in cats, pretreated with HES-DFO, using both the vascular ligation and the increased intraocular pressure models. Retinal recovery was monitored by electroretinography. Fundal fluorescein angiography was performed in treated and untreated animals after ischemia-reperfusion. RESULTS: Our results indicate that pretreatment with an intravenous bolus of HES-DFO, significantly enhances recovery of the postischemic b-wave and decreases fluorescein leakage after ischemia-reperfusion. CONCLUSIONS: HES-DFO improves recovery of the neural retina after ischemia-reperfusion. It also maintains the integrity of the blood-retinal barrier. The protective effect of HES-DFO on the blood-retinal barrier is consistent with its intravascular confinement. That HES-DFO results in protection of the neural retina underscores the importance of the blood-retinal barrier as a mediator of ischemia-reperfusion injury. HES-DFO may have a role in the early management of ischemic retinal disease both as an iron chelator and as a blood-retinal barrier protector.
PURPOSE: The iron chelating agent deferoxamine mesylate USP (Desferal, Ciba, Summit, NJ) is commonly used in the treatment of acute iron intoxication and chronic iron overload (associated with the transfusion-dependent anemias). When used for prolonged periods of time or in high doses deferoxamine is attended by a range of ocular toxicities. The visual symptoms associated with deferoxamine administration often limit effective iron chelation therapy and can result in permanent vision loss. Deferoxamine has recently been conjugated to certain high molecular weight biocompatible polymers without altering its iron-binding properties. Here the effect of conjugation of deferoxamine to hydroxyethyl starch on retinal toxicity is examined. METHODS: An albino rat model of electroretinographically determined, deferoxamine-induced retinal toxicity has been previously described. We use this model to evaluate and compare both native deferoxamine and hydroxyethyl starch conjugated deferoxamine. RESULTS: Our data show that retinal function, as assessed by the electroretinogram b-wave, is significantly depressed 1 day after a single dose of native deferoxamine, while the b-waves of rats receiving a single dose of hydroxyethyl starch-deferoxamine, are not significantly depressed at any time during the study. In addition, the administered dose of hydroxyethyl starch-deferoxamine resulted in plasma deferoxamine concentrations up to five times greater than those achieved with native deferoxamine. CONCLUSION: These results suggest that hydroxyethyl starch conjugated deferoxamine is associated with less retinal toxicity than native deferoxamine and that it may be a safer alternative for iron chelation therapy.
PURPOSE: To examine a photoelectric artifact associated with the ERG-jet corneal contact lens electrode (Universe SA, La Chaux-de-Fons, Switzerland). METHODS: An artifact associated with the ERG-jet, gold foil corneal contact lens electrode was reproduced in vitro and in vivo using 50 msec light flashes. In vitro responses were examined using light flashes that varied in intensity, duration, and wavelength. Ionic strength of the bathing solution and temperature dependence were also examined. In vivo responses were compared to similarly recorded signals using the Burian-Allen bipolar electrode. RESULTS: The artifact is not apparent with microsecond light flashes, as with the Grass PS22 Photo-stimulator connected to a Ganzfeld. Longer light flashes and increasing light intensities, however, elicit graded responses that may resemble the late PIII component of the ERG in profile and in magnitude. The artifact varies with temperature, ionic concentration of the bathing medium, and wavelength of stimulating light. The artifact also varies in magnitude and polarity from one disposable electrode to the next. Light flashes of shorter wavelengths elicit greater responses than light flashes of equal radiant energy but of longer wavelengths. CONCLUSIONS: The artifact derives from electrode polarization occurring at the interface between the gold foil and its ionic medium. Caution is required when using light stimuli longer than 2-3 msec with this and similar types of intrinsically polarizable metal electrodes.
Metabolic correction and physiologic response were evaluated after bone marrow transplantation in mucopolysaccharidosis. Eleven patients were prospectively evaluated to determine the effect of bone marrow transplantation on the progressive ocular manifestations of these disorders. Follow-up of 0.6 to 2.8 years after successful donor stem cell engraftment showed that some patients had slow clearing of the corneal clouding, reduction of intracytoplasmic inclusions in the conjunctiva, resolution of optic nerve edema, and stabilized or improved retinal function as determined by electroretinography. These preliminary results suggest that early bone marrow transplantation may alter some of the progressive ophthalmic characteristics of the mucopolysaccharidoses. Long-term follow-up is necessary to determine if these early alterations in the ocular features are predictive of a prolonged functional improvement in the visual status.
Arterial perfusion of the isolated cat eye with a perfusate augmented with a 20% (wt/vol) emulsion of the oxygen carrying-fluorocarbon, FC43, produces a much larger b-wave in the electroretinogram than use of the same perfusate lacking FC43. The c-wave is either unchanged or slightly reduced by use of this solution. Halving the oxygen content of the FC43-augmented perfusate also reversibly reduces the b-wave. The use of perfusates with and without FC43 but containing similar amounts of oxygen produces b-waves of similar amplitude. The large b-wave recorded during use of a well-oxygenated, FC43-augmented perfusate suggests that the use of perfusates containing less oxygen produces retinal hypoxia. The b-wave recorded in vivo is considerably smaller than that recorded from the isolated eye during perfusion with a well-oxygenated, FC43-augmented perfusate, but the waveforms are very similar. In particular, the ratios of the b-wave to a-wave are almost identical. The larger ERG recorded in vitro is a result of increasing the shunt resistance to ground upon enucleation. Histological examination of retinas perfused for two hours with the FC43-augmented and standard perfusate reveal no clear signs of tissue hypoxia in either retina. However, even two hours of complete ischemia produces limited inner retinal deterioration and virtually no outer retinal damage, suggesting that the histological state of the retina may not be a reliable indicator of its physiological state. Despite the improved electrophysiological state of the retina produced by increasing its oxygen supply, the survival time of the isolated eye was not increased.
The ultrastructure of single and twin cone photoreceptors in the retina of the walleye was analyzed by scanning and transmission electronmicroscopy. The outer segment disks resemble those of other vertebrates. An accessory outer segment arises from the inner segment, makes frequent contacts with the outer segment proper, and may thus provide a bridge for signal transmission from outer to inner segment. A palisade of some 30 calycal processes surrounds and may provide structural support for the outer segment. The region of apposition between the inner segments of twin cones consists of a space of some 28 nm with no indication of gap junctions. The proximal quarter of the inner segment displays a profusion of some 50 lateral fins which increase the inner segment surface by 3-4 X and do not contact fins of neighboring cones. The fins surround a profusion of Müller cell microvilli and probably promote metabolic exchange between cones and Müller cells. Apart from differences in size and the presence of apposed inner segments, twin and single cones appear to be morphologically similar.
Three features appear to characterize steady-state light adaptation in vertebrate cone photoreceptors: (a) the shape of the "log intensity-response" curve at different levels of adaptation is the same, the only change with adaptation is in the position of the point on the curve about which the cones operate; (b) at high adapting intensities the operating point becomes fixed in position; (c) this fixed position is at the steepest point of the log intensity-response curve. These three features can be described by a mathematical model.
We studied 13 patients, six males and seven females, ranging in age from 14 to 53 years, with chronic pars planitis and a form of secondary retinal degeneration. All had experienced visual blurring but none had significant pain. Nine of the 13 had some disturbance in night vision. Visual acuity had decreased in three patients (in one because of cataract, in one because of cystoid macular degeneration, and for unknown reasons in the third), increased in two patients (because of improvement in cystoid macular edema), and remained stable in eight. There were electrophysiologic abnormalities, consisting of delayed B-wave implicit time, abnormal response to 30-Hz flicker, and reduced B-wave oscillations, in almost every patient. Our finding suggested that pars planitis is a vitreoretinal disorder rather than an inflammatory disease of the uveal tract.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Clinical electro-oculograms (EOGs) were recorded from six normal subjects over 24 hr time periods for a total number of 70 EOG'S. Results indicate an inverse relationship exists between the light/dark (L/D) ratio and the dark-trough potential. No relationship was found between the light-peak potential and the L/D ratio. Both the dark-trough potential and the L/D ratio showed a circadian periodicity over working daylight hours and rather aberrant behavior in late evening and early morning hours. Circadian contributions to the L/D ratio are estimated to be between 20% and 50% of the total variability in the normal individuals studied. We suggest the optimal time for single measurements of EOG pathology should be around midday.
Responses of BG-G units to equal energy stimuli of different wavelengths reveal a tonic to phasic pattern of responses in which short wavelengths (blue) evoke tonic activity, medium wavelengths (green to yellow) evoke phasic activity and intermediate wavelengths evoke in-between patterns. The patterns correlate with wavelength but are relatively insensitive to intensity. Output patterns of BG-G cells to white and to monochromatic light at the animal's neutral point are almost identical, and the pattern identities may be a neural correlate to the behavioral phenomenon of the neutral point.
Explore the source record for details and available documents.
The end-stage or involutional phase of proliferative diabetic retinopathy may result in stabilization of vision for long periods of time. However, the clinical resemblance to the progressive tapetoretinal degenerations suggests that marked functional impairment of the retina is present in such eyes. We studied 19 eyes with involutional retinopathy to document the status of the retinal function. Studies included fluorescein angiography, visual field examination, dark adaptation testing, color vision testing, electro-oculography and electroretinography (ERG). The results indicated marked functional abnormalities in all eyes. The ERG tracings showed uniformly subnormal responses and delayed implicit times, similar to those of dominantly inherited retinal pigment degeneration, and indicative of a progressive retinal disorder. In two patients, color vision testing showed defects similar to those seen in inherited tritanopia; and in the remaining patients, defects were indicative of an acquired blue-yellow dyschomatopsia.
Recognition of nonlinearities in the neuronal encoding of repetitive spike trains has generated a number of models to explain this behavior. Here we develop the mathematics and a set of tests for two such models: the leaky integrator and the variable-gamma model. Both of these are nearly sufficient to explain the dynamic behavior of a number of repetitively firing, sensory neurons. Model parameters can be related to possible underlying basic mechanisms. Summed and nonsummed, spike-locked negative feedback are examined in conjunction with the models. Transfer functions are formulated to predict responses to steady state, steps, and sinusoidally varying stimuli in which output data are the times of spike-train events only. An electrical analog model for the leaky integrator is tested to verify predicted responses. Curve fitting and parameter variation techniques are explored for the purpose of extracting basic model parameters from spike train data. Sinusoidal analysis of spike trains appear to be a very accurate method for determining spike-locked feedback parameters, and it is to a large extent a model independent method that may also be applied to neuronal responses.
Techniques developed for determining summed encoder feedback in conjunction with the leaky integrator and variable-gamma models for repetitive firing are applied to spike train data obtained from the slowly adapting crustacean stretch receptor and the eccentric cell of Limulus. Input stimuli were intracellularly applied currents. Analysis of data from cells stringently selected by reproducibility criteria gave a consistent picture for the dynamics of repetitive firing. The variable-gamma model with appropriate summed feedback was most accurate for describing encoding behavior of both cell types. The leaky integrator model, while useful for determining summed feedback parameters, was inadequate to account for underlying mechanisms of encoder activity. For the stretch receptor, two summed feedback processes were detected: one had a short time constant; the other, a long one. Appropriate tests indicated that the short time constant effect was from an electrogenic sodium pump, and the same is presumed for the long time constant summed feedback. Both feedbacks show seasonal and/or species variations. Short hyperpolarizing pulses inhibited the feedback from the long time constant process. The eccentric cell also showed two summed feedback processes: one is due to self inhibition, the other is postulated to be a short time constant electrogenic sodium pump similar to that described in the stretch receptor.