Biomedical subjects
M F Marmor
Publications and source records attributed to M F Marmor.
Electrophysiological correlates of rod outer segment disc shedding in rabbit retina.
We hypothesize that the b-wave of the electroreginogram (ERG) can provide a precise, noninvasive measure of the morning rod disc shedding event. ERGs were recorded in the dark from photoentrained rabbits using a 500 nm test light. Histological examination of the pigment epithelium confirmed that an increase in large phagosome content occurred shortly after light onset. In albino rabbits the b-wave decreased in amplitude at about 30 min after the time of normal light onset. The corresponding decrease in sensitivity required to produce this change in amplitude was 0.11 log unit. No ERG effect was seen in pigmented rabbits.
Electroretinographic assessment in schizophrenia.
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Effects of intraocular pressure and other factors on subretinal fluid resorption.
We observed the effects of intraocular pressure (IOP), vitreous pressure and gravity on the resorption of small retinal detachments (blebs) made with Hanks' solution or autologous serum. Raising the IOP decreased the absorption time moderately and lowering the IOP increased it. These effects were greater when the RPE had been damaged by sodium iodate or laser burns, but we conclude that IOP makes only a small, limited contribution to normal subretinal fluid absorption. Neither liquefaction of the vitreous nor retinal weight had a significant influence on fluid absorption.
Pharmacologic modification of subretinal fluid absorption in the rabbit eye.
We studied in the rabbit the effects of pharmacologic agents on the absorption of Hanks' solution from the subretinal space of experimental nonrhegmatogenous detachments. Intravenous acetazolamide had no effect at a clinical dose (15 mg/kg) but increased the rate of fluid absorption significantly at high doses (50 mg/kg). Acetazolamide causes systemic pH to fall, while PCO2 and PO2 increase; however, duplicating some of these effects by artificial respiration or breathing 95% O2 plus 5% CO2 did not alter the rate of fluid absorption. Adding cyclic AMP and related agents to the vitreous and subretinal space slowed down fluid absorption by 25%, whereas cyclic GMP analogues increased the rate of absorption by 33%.
Contrast sensitivity versus visual acuity in retinal disease.
A large group of individuals with retinal disease were tested prospectively for contrast sensitivity by means of Arden gratings. A subgroup of 19 were also tested with the Nicolet automated television system. Individuals with macular or peripheral dystrophy showed a general reduction in contrast sensitivity as visual acuity decreased. The loss of contrast sensitivity was more prominent for high spatial frequencies (6.4 cycles per degree) than for low ones (0.2 cycles per degree). Similar results were obtained for patients with achromatopsia and congenital stationary night blindness. Patients with functional complaints, but no organic basis for decreased acuity, showed greater scatter in their test scores. The Nicolet results showed somewhat smoother curves, but were no more specific in separating normality from abnormality. Contrast sensitivity testing was not specific for the retinal disease entities considered, but may be useful in recording a degree of retinal damage and a degree of functional visual disability. Contrast sensitivity appeared to be reduced whenever acuity was reduced, so that a distinction could be made between patients having a loss of contrast beyond the expectations for their level of acuity and those in whom a loss of contrast simply corroborates the reduction of acuity.
Mechanisms of subretinal fluid resorption in the cat eye.
Small, non-rhegmatogenous retinal detachments (blebs) were made in cat eyes by injecting fluid into the subretinal space, and the time course of fluid resorption was monitored. Blebs made with Hanks' solution over the pigmented RPE resorbed 22% faster than those over the tapetum. Blebs made with a non-ionic solution (isotonic sucrose) took 43% longer to resorb than those made with Hanks' solution, and blebs containing 3 X 10(-3) M sodium cyanide took 32% longer than controls. These results suggest that active ionic transport is involved in the absorption of subretinal fluid in the cat, as it is in the rabbit. Oncotic pressure in the choroid may also contribute to resorption, because blebs made with autologous serum took roughly 3 times longer to resorb than those made with non-proteinaceous Hanks' solution. The retinal vascular system does not appear to contribute, since the resorption time was similar for Hanks' blebs made under normal retina and those made under ischemic retina (produced by occluding retinal branch arteries with argon laser photocoagulation or endodiathermy).
Quantitative estimation of metabolic transport of subretinal fluid.
A new technique to measure the ongoing rate of subretinal fluid resorption inside the living eye is described. Experimental non-rhegmatogenous detachments (blebs) were made in the posterior pole of rabbit eyes by injecting fluid directly into the subretinal space, and the height of these blebs was measured with a YAG laser focusing system utilizing dual He-Ne beams. The resorption rate for Hanks' balanced salt solution was relatively constant during the initial 2.5 hr, and averaged 0.12 +/- 0.04 microliter/mm2/hr. The resorption rate for blebs made with non-ionic solution (isotonic sucrose) was only 0.03 microliter/mm2/hr. The resorption rate for blebs made with Hanks' solution plus 1 mM DNP was 0.04 microliter/mm2/hr. These data support the concept that subretinal fluid is resorbed primarily across the retinal pigment epithelium, and suggests that 70% of this absorption is dependent upon active ionic transport. The remaining 30% is probably driven by the higher oncotic pressure of the choroid.
Acute changes in RPE apical morphology after retinal detachment in rabbit. A SEM study.
The morphology of the apical surface of rabbit retinal pigment epithelium was studied by scanning electron microscopy from the first minute to several hours after making small nonrhegmatogenous retinal detachments (blebs). From 0 to 5 min, there were only slight changes in the homogeneous, dense mat of filamentous microvilli. From 5 to 30 min, filamentous microvilli retracted exposing larger processes. From 30 to 60 min blunt processes became completely exposed and sheet-like processes disappeared. At about 60 min, cone sheaths were no longer identifiable in most specimens. Between 60 min and the time of retinal reapposition (several hours), the apical surface became highly rounded. Colchicine and cytochalasin-D had no effect on the time required for fluid resorption, but colchicine greatly accelerated and enhanced cell rounding, while cytochalasin-D produced prominent apical tufts.
Effects of hypoxia and hyperoxia on the human standing potential.
We report that the human standing potential, measured by the EOG, rises slowly when oxygen saturation is lowered to near 80% by breathing a controlled oxygen-nitrogen mixture. The standing potential falls abruptly by 20-30% of its amplitude when the oxygen saturation returns to 100%. These changes can be generated reproducibly, with minimal discomfort, under conditions that could be adopted for clinical use. Animal experimental studies by Linsenmeier and Steinberg suggest that this hypoxia-hyperoxia response may be a delayed response to potassium concentration changes in the subretinal space. Since there is no requirement for light and no involvement of the Müller cells, the hypoxia-hyperoxia response may be more specific for pigment epithelial pathology than the c-wave.
Kinetics of macromolecules injected into the subretinal space.
Small, experimental, non-rhegmatogenous retinal detachments (blebs) in rabbit eyes resorbed 50% more slowly when filled with autologous serum than with Hanks' solution. To study the fate of large molecules in the subretinal space, carboxyfluorescein and several sizes of FITC-dextrans were injected into blebs and their movement followed by fluorophotometry. Carboxyfluorescein diffused quickly into the vitreous and was gone from the space after 8 hr. FITC-dextran 10-S (smaller than albumin) also diffused readily into the vitreous and took about 30 hr to be eliminated from the subretinal space. The diffusion of FITC-dextran 70-S and 150-S (both larger than albumin) was markedly slower, and roughly 80% of the 150-S was still present in the subretinal space after 3 days. Since the subretinal fluid in all of these blebs resorbed within 10 hr, the physiologic mechanisms for fluid resorption and elimination of large substances appear to be independent. Damaging the RPE barrier with sodium iodate allowed even the larger FITC-dextrans to exit from the subretinal space.
The eyes of Woodrow Wilson. Retinal vascular disease and George de Schweinitz.
Woodrow Wilson suffered a retinal hemorrhage in 1906, which is central to a historical controversy over whether medical problems significantly affected his political behavior prior to his stroke of October 1919. In terms of modern knowledge, the most likely cause of the event of 1906 is a retinal vein occlusion. Confidence in this judgment is gained from evidence that George de Schweinitz, one of the prominent ophthalmologists of his day, examined Wilson and showed through writings that he was well aware of the major categories of retinal vascular disease that are recognized today. Wilson was also subject to more ordinary problems, illustrated by anecdotes about his refractive errors, difficulty in learning to read, asthenopic symptoms, and visual problems with golf.
Cilioretinal collateral circulation after occlusion of the central retinal artery.
Two elderly patients were noted to have unilateral central retinal arterial narrowing with cilioretinal arterial collaterals supplying the bulk of the flow to the inner retina. One patient had excellent acuity and normal pupillary reactions; the other had marked impairment of vision and an afferent pupillary defect. Both patients were asymptomatic. We suggest that these patients had gradual or partial central retinal arterial occlusion which allowed the development of a collateral arterial supply from the ciliary system.
Barriers to fluorescein and protein movement.
Vitreous fluorophotometry assesses the leakage of fluorescein through the primary blood-retinal barrier composed of retinal capillaries and the pigment epithelium. However, other ocular barriers exist that may differentiate between the small molecules of fluorescein and the larger ones of protein. We injected solutions containing carboxyfluorescein and several sizes of fluoresceinated dextran into the subretinal space of rabbit eyes. Carboxyfluorescein diffused rapidly through the retina into the vitreous, but dextrans of a size comparable to proteins crossed the retina very poorly. Large dextrans persisted for days in the subretinal space, although the fluid injected with them disappeared within a few hours. Vitreous fluorophotometry must be interpreted with the knowledge that the retina is much more of a barrier to protein than to fluorescein.
Experimental serous retinal detachment and focal pigment epithelial damage.
We made small nonrhegmatogenous retinal detachments (blebs) in rabbits over regions of retinal pigment epithelium (RPE) that were damaged mechanically or by laser photocoagulation. Fluorescein diffused readily into blebs made over damaged RPE, but the subretinal fluid was resorbed more quickly than from blebs overlying normal RPE. Thus, focal damage appears to facilitate water movement from, rather than into, the subretinal space. We conclude from these data that central serous chorioretinopathy is not caused simply by a passive "leak" through the RPE barrier, and the effects of photocoagulation in this disease cannot be explained simply as sealing such a leak.
Selective actions of barium on the c-wave and slow negative potential of the rabbit eye.
The c-wave and slow negative potential (incorporating the slow P111) are both thought to be generated by light-evoked changes in the concentration of potassium surrounding the photoreceptors. We find the intravitreal barium, a blocker of potassium conductance, eliminates the c-wave from the intact rabbit eye but not the slow negative response. However, if the pigment epithelium is damaged by systemic administration of sodium iodate, barium then eliminates the slow negative response.
Healing of photocoagulation lesions affects the rate of subretinal fluid resorption.
We have measured the rate of subretinal fluid resorption in rabbits by monitoring the collapse of small experimental retinal detachments (blebs) filled with either Hanks' solution (non-proteinaceous) or autologous serum. Blebs filled with Hanks' solution resorbed much more rapidly over freshly lasered RPE than normal RPE, but the effect disappeared over 10 to 14 days. This time course corresponds with angiographic and histologic evidence of RPE repair. In contrast, blebs filled with serum resorbed at nearly the same rate regardless of whether the RPE had been lasered or not. We conclude that photocoagulation destroys the RPE barrier acutely, and until the barrier heals non-proteinaceous subretinal fluid will be drawn out rapidly by the oncotic pressure of the choroid. This acute effect of photocoagulation is of uncertain benefit in clinical conditions because of protein in the subretinal fluid, and it seems more likely that photocoagulation works in serous retinopathy by arresting an active source of fluid.
Validation of a model of non-rhegmatogenous retinal detachment.
To study the movement of subretinal fluid, we have injected fluid into the subretinal space through a glass micropipette and monitored its resorption. This technique has been criticized as a model of non-rhegmatogenous detachment because the small retinal hole made by the micropipette might allow efflux of subretinal fluid into the vitreous. The present experiments answer this criticism: we found that sealing the micropipette hole with cyanoacrylate, mucilage or an air bubble had no effect on the rate of subretinal fluid resorption, and detachments with two to five micropipette holes did not resorb faster than those with only one.