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Biomedical subjects

W W Dawson

Publications and source records attributed to W W Dawson.

At least 37 records · Page 2Linked to original sources

The quantity of rhodopsin in human eyes.

The content of rhodopsin in the eyes of 15 donors (30 eyes) was determined. Both retinal and pigment epithelial fractions were collected from each globe, extracted using 1% CTAB, and the rhodopsin difference spectrum of each fraction was obtained separately. The total amount of rhodopsin, obtained by summing the amounts recovered from the retinal and PE fractions, ranged from 2.00 to 11.94 (median: 6.40) nmoles/eye. Previously reported mean values of about 3.5 to 4.0 nmoles per retina have been obtained using a variety of methods. The present higher values, perhaps largely dependent on procedural details described herein, appear plausible given the known concentrations of rhodopsin in rod outer segments, rod outer segment volumes, and number of rods in the human retina.

Adult↗

Macular disease in related rhesus monkeys.

During (January) 1986-(May) 1988, we examined 272 eyes in 136 rhesus monkeys in the closed Cayo Santiago colony of the Caribbean Primate Research Center of the University of Puerto Rico. Seventy-eight eyes were less than 10 years of age. One hundred and ninety-four were aged 10-28 years. The fundi were examined and photographed. Fluorescein angiography was performed in some eyes. Selected cases were evaluated for 'acuity' loss by recording of pattern-evoked retinal and cortical signals. Light and electron microscopy were used to evaluate the pigment epithelium of some animals. Thirty-eight percent of all eyes had posterior pole drusen. Incidence was highly age-related. When late-stage lesions were found, we did not see neovascularization, but late hyperfluorescence was consistent with degenerative scarring and atrophy. Electrophysiology demonstrated moderately reduced acuity in the presence of numerous macular drusen. Electrooculograms were low normal. Histopathology showed changes identical to those reported in human age-related macular degeneration. No eyes less than 10 years of age had confluent drusen or disciform-like lesions. The incidence of drusen in samples of some social groups was much higher than others.

Age Factors↗

Very large neurons of the inner retina of humans and other mammals.

Large ganglion cells, called parasol cells, are known to occur in the Golgi-stained, human retina. This report describes a population of much larger cells that is not stained by Golgi technique. These cells may be located in the human ganglion cell layer using Nomarski differential interference contrast optics and unstained, flatmounted tissue. These cells are regularly distributed in young and old adults in a Gaussian fashion along the radii that extend from the perimacula toward the far periphery. The author did not find the cells in the central retina. The most frequent (J-type) cells have soma diameters between 26 and 40 microns. Rare (S-type) cells measure up to 55 microns in diameter. Many cells have processes that appear to be axons or dendrites. These cell types may be especially sensitive to damage early in diseases of the inner retina.

Adult↗

Adult-onset macular degeneration in the Cayo Santiago macaques.

Since 1985 a group from the University of Florida has examined 136 rhesus monkeys from the Cayo Santiago colony. From the sample, 97 are older than nine years (approximately 30 human years) and 39 are younger. Drusen were found in 17% of the younger eyes and in 46% of the older eyes. All animals over 25 years of age had drusen in the central fundus. The incidence of drusen varied from 19-77% between five social groups. Incidence reported in random-source colonies in the continental U.S.A. is about six percent. Compared to near-age matched controls without drusen, selected rhesus exhibited visual resolution losses amounting to two Snellen-lines or more. The end-stage disciform changes and ultrastructural similarities are comparable with human macular disease. Future prospective studies may include therapies, surgical intervention, environmental manipulation and genetic research.

Academies and Institutes↗

Electroretinograms in early fungal endophthalmitis.

To facilitate the early diagnosis of exogenous fungal endophthalmitis, we developed a rabbit model for Aspergillus fumigatus endophthalmitis. Six eyes of six New Zealand white rabbits were inoculated with forty spores of A. fumigatus. A control group of their six contralateral eyes received a similar but sterile inoculum. The rabbit eyes were evaluated with respect to clinical appearance and the electroretinogram. Clinically evident endophthalmitis developed in all six infected eyes at an average of five days after injection (range 3-7 days). Data samples each 48 hours showed transient b-wave amplitude elevations in three infected eyes. These were greater than two standard deviations above the mean pre-injection values (p less than 0.05). These amplitude increases preceded the onset of ophthalmoscopically recognizable infection and were observed at 2 to 5 days after injection (mean = 4 days). B-wave amplitudes in the infected eyes fell below two standard deviations of pre-injection values (p less than 0.05) at an average of 5 days (range 3-7 days) after injection, a corresponding to the onset of clinically obvious infection. At an average of 7 days after injection, all the infected eyes exhibited unmeasurable electroretinogram waveforms and severe infection. Histopathologic study of infected eyes showed extensive fungal infiltration of retina and vitreous tissues. The electroretinogram may be helpful in the early diagnosis of fungal endophthalmitis.

Animals↗

Division of the pattern-evoked retinal response by respiratory acidosis.

Analysis in the frequency domain divided the pattern-evoked retinal response (PERR) of the cat into two analog components. A mild respiratory acidosis was produced by raising the end-tidal CO2 from 4-6% to 12-14%. The onset of the acidosis (without hypoxia) was highly correlated with marked decreases in the low-frequency PERR component and in the b-wave of the flash-elicited ERG. The high-frequency PERR component was unchanged relative to the labile low-frequency component (p less than 0.01). The literature has established a firm link between local pH and Müller cell function. These data tend to confirm the hypothesis that the cat's PERR to some grating stimuli of less than 100% contrast may contain separable components of different cellular origin(s).

Acidosis, Respiratory↗

Electroretinal changes in the presence of a carbonic anhydrase inhibitor.

A specific carbonic anhydrase activity inhibitor (methazolamide) was injected into one vitreous body each of 4 New Zealand White rabbits. Electroretinograms (ERG) were recorded before and several times after the methazolamide injection. The stimulus levels maximized the rod and cone response characteristics of the rabbit ERG. The effects of methazolamide were followed over 5 h. During this time, the electroretinograms showed a decline in amplitude of both a and b waves at both stimulus levels. The data support the involvement of carbonic anhydrase in the excitatory physiological events in the retina. Preliminary evidence indicates a slow recovery of the carbonic-anhydrase-inhibited ERG.

Animals↗

Degenerative changes in maculas of rhesus monkeys.

In the hope of identifying an animal model for age-related macular degeneration (AMD) we undertook a pilot investigation of aged rhesus monkeys. Twenty-nine monkeys from a seminatural colony were examined at the Caribbean Primate Research Center. Macular drusen were found in 74% of the monkey eyes. Alterations of the retinal pigment epithelium within the macula were noted in 45% of the eyes. Fluorescein angiography in selected animals revealed window defects consistent with drusen. None of this sample showed the exudative form of AMD or disciform scarring. One typical monkey underwent special studies including measurement of visual resolution by electrophysiological study of the retinal and visual cortex. Application of human criteria to this animal supported the diagnosis of early AMD. Histopathologic study of one eye by transmission electron microscopy confirmed the presence of drusen with nearly identical ultrastructural features to those found in the human pigment epithelium in AMD.

Aging↗

Pattern electroretinogram: effects of reference electrode position.

The pattern electroretinogram has assumed greater clinical and experimental significance because of its inner retinal origins. However, clinical tests may be confounded by an artifact. We tested subjects varying reference electrode position and eye stimulated while employing the Dawson-Trick-Litzkow (DTL) fiber electrode as the active electrode. The presence of a statistically significant artifactual response could not be confirmed. However, the variability of responses elicited with the outer canthus was less and the signal-to-noise ratio greater than with other reference positions.

Analysis of Variance↗

Cyclic light intensity threshold for retinal damage in albino rats raised under 6 lx.

This study determined the minimum cyclic (12L:12D) light intensity which produces retinal damage in albino (Sprague-Dawley) rats raised from birth to 15 weeks of age under 6 lx (12L:12D). Four experimental light intensities were tested, viz. 1345, 270, 130 and 65 lx. Control animals remained under 6 lx. After various durations of exposure to one of the intensities tested, the retinas of groups of six rats were evaluated for physiological and morphological evidence of light damage. The indices of damage were: (1) histological and morphometric changes in the retina, and (2) changes in the amplitude and latency of the b-wave of the electroretinogram. Light intensities of 1345- or 270 lx severely damage retinas of albino rats raised from birth under 6 lx within 3-7 days of the initiation of light exposure. Exposure to 130- or 65 lx produced much less dramatic changes in the responsiveness and morphology of the retina that did not appear to be permanent. Based on these results, a reasonable estimate for the threshold cyclic-light intensity which produces damage to retinas of albino rats raised under 6 lx lies between 65- and 130 lx, or slightly more than 1 log unit above the light intensity under which the animals were raised. The effects of an animal's light history on retinal susceptibility to light damage are discussed.

Animals↗

Infrared. An unseen and unnecessary hazard in ophthalmic devices.

The concept of instrument-induced light damage to the retina is well established. Many have argued that ultraviolet (UV) energy is overwhelmingly responsible and that longer wavelength infrared (IR) energy causes thermal change and plays a minimal role. We suggest that infrared may play a primary role in instrument-induced damage. We measured the radiometric and photometric outputs from commonly used ophthalmic devices in normal use and in IR-blocked conditions. We found IR output to represent a significant portion of the total irradiation produced by these instruments. Infrared was easily and inexpensively minimized without compromising usable visible light in these instruments using an efficient IR filter. The instruments' incandescent lamps, glass envelopes, and optics are poor UV emitters or transmitters. Manufacturers' data do not indicate UV emission. Evidence for UV blocking and IR transmission by the intraocular media is presented.

Infrared Rays↗

Macular degeneration in a community of rhesus monkeys. Ultrastructural observations.

The eyes of 29 aged adult, (mean age, 20 years) rhesus monkeys were examined for the presence of age-related macular degeneration (AMD). This sample represented approximately 25% of the aged population in the seminatural colony at the Caribbean Primate Research Center (CPRC) of the University of Puerto Rico. Approximately 75% of the animals examined had drusen in the posterior pole. Ultrastructural analysis was used to determine whether the pathologic alteration of Bruch's membrane and drusen in the colony resembled those noted in aged or AMD-afflicted human retinas. There were abnormalities in all layers of Bruch's membrane. Deposits of heterogeneous material, comprised of membranous, granular, and cellular components, were seen in both the inner collagenous zone (ICZ) and the outer collagenous zone (OCZ). Accumulation of this drusenoid material in the ICZ produced a scalloping of the basal border of the retinal pigment epithelium (RPE). Dense bodies were seen in both Bruch's membrane and RPE cytoplasm near the basal infoldings. Cytoplasmic processes, as well as whole cells, were seen with regularity within the drusenoid material. In one case there was a cell with a basement membrane crossing the middle elastic layer of Bruch's membrane. These changes are consistent with those reported in human aging and AMD. Aged individuals in this colony appear to be predisposed to macular degenerative changes and may prove to be an invaluable animal model for studying AMD in humans.

Animals↗

Retinal cyclic light damage threshold for albino rats.

This study determined the minimum cyclic [12L:12D] light intensity which produces retinal damage in albino (Sprague-Dawley) rats raised from birth to 15 weeks of age under a cyclic light intensity of 6 lux. Four experimental light intensities were tested, including: 1345, 270, 130 and 65 lux. Control animals remained under 6 lux. For each of the intensities tested, the retinas of groups of six rats were evaluated after various durations of light exposure for physiological and morphological evidence of light damage. The indices of damage were (a) histological and morphometric changes in the retina and (b) changes in the amplitude of the b-wave of the electroretinogram. The data indicated that light intensities of 1345 or 270 lux severely damaged retinas of albino rats within 3-7 days of the initiation of light exposure. Exposure to 130 or 65 lux produced much less dramatic changes in the responsiveness and morphology of the retina which did not appear to be permanent. Based on these results, a reasonable estimate for the threshold cyclic light intensity which produces damage to retinas of albino rats raised under 6 lux lies between 130 and 270 lux, or approximately 1.3 log units above the light intensity under which the animals were raised.

Animals↗

The effects of dim cyclic light on pigment epithelial function in the albino rat.

Most pathologies of the outer retina include physiological and morphological changes in the pigment epithelium. The question of pigment epithelial involvement in retinal light damage caused by low intensities of light is still unresolved. In the present study, we investigated the effects of low intensity cyclic light on pigment epithelial function in albino rats. The functioning of the pigment epithelium was assessed electrophysiologically from d.c. recordings of ERG c-waves and sodium azide induced changes in the resting potential. Responses obtained from albino rats raised under low intensity cyclic light (0.63 ft cd. 12:12 L:D) were compared to those obtained from albino rats raised under minimal light exposure conditions (dark-reared) and pigmented rats housed under low intensity cyclic light. We report, for the first time, that albino rats raised from birth under low intensity cyclic light possess c-waves. Their responses were comparable in amplitude and latency to those recorded from pigmented rats housed under similar conditions, but were significantly smaller than those recorded from dark-reared albino rats. The reduction in the amplitudes of the c-waves recorded from cyclic light-reared albino rats was probably not due to retinal light damage. Comparisons of the amplitudes and latencies of ERG b-waves recorded from cyclic light-reared and dark-reared albino rats did not suggest that the retinas of the cyclic light-reared albino rats had been damaged by light. Light microscopic examination of these retinas also provided no evidence for light damage. The transient, positive potential changes recorded from cyclic light-reared albino rats in response to bolus injections of sodium azide were significantly smaller than those recorded from either dark-reared albino rats or pigmented rats housed under low intensity cyclic light. The results of these experiments suggest that the pigment epithelium of albino rats is functionally altered by extremely low intensities of cyclic light.

Albinism↗

Tissue responses of the monkey retina: tuning and dependence on inner layer integrity.

Recent technical and conceptual advances have made it possible to experiment with models of local human inner retinal disease and changes in very small, tissue-specific signals. Local retrograde degeneration of the ganglion cells was induced in four rhesus monkeys by 160 degrees microdiathermy fiber layer burns at the nasal or temporal edges of the optic disc. There were no abnormalities of the classical electroretinograms (ERGs) during the following 210 days. With nasal lesions, pattern-evoked retinal (PERR) and cortical responses over a range of grating contrasts and spatial frequencies were largely normal. The authors found a cortical spatial tuning peak near 0.5 cycles/deg (cpd) and a retinal peak at 0.25-0.3 cpd. With temporal lesions, the retinal signals to high frequency stimuli (greater than 1.0 cpd) approached zero between 20-60 days. The cortical evoked signal declined with a course similar to the retinal components. Histological evidence was found for extensive loss of ganglion cells and fibers in a central 30-40 degrees temporal area, including the macula, 210 days after the temporal lesions. This is strong evidence that local ganglion cell-dependent electrical potentials, bearing little relation to the ERG, can be measured in response to selected stimuli.

Animals↗

Disease-specific electrophysiological findings in adult ceroid-lipofuscinosis (Kufs disease).

Two adults with mild dementia and a history of memory loss and disequilibrium were seen in the eye clinic following complaints of acuity loss in the 20/30-20/70 (Snellen) range. Results from the fundus examination of one patient were entirely normal; the other showed minimal vascular attenuation and optic atrophy. Electrophysiology was remarkable: (1) Photopic ERG b-waves were reduced, delayed, and showed pronounced oscillations. (2) EOG 'light-rise' potentials were absent or very small. (3) Binocular pattern-VER signals showed addition of the monocular signal. Scotopic ERG signals were normal. Brain biopsy and microscopy showed intercellular, autofluorescent ceroid deposits which provided a clear diagnosis of Kufs disease. Histology of model animal retinal cells show ceroid deposits in cell classes implicated by the human retinal signals. The cluster of electrophysiological results point toward early changes in the pigment epithelium and inner plexiform layer cells as a means of noninvasive diagnosis.

Adult↗

Culture of retinal pigment epithelium from chorio-retinal biopsies.

The recently devised methods for surgical sampling of chorio-retinal tissue permits morphological evaluation of retina in various diseases. In the present report it is demonstrated, that the retinal pigment epithelium in such samples can be isolated as a viable cell population, and that the cell mass can be increased sufficiently in culture to permit biochemical as well as morphological studies. This procedure thereby expands the diagnostic potential of the sample tissue.

Animals↗

Retinal pigment epithelial dysfunction in early ovine ceroid lipofuscinosis: electrophysiologic and pathologic correlates.

Retinal degeneration is a major finding in the human and ovine ceroid lipofuscinosis. Sequential electroretinographic (ERG) studies in a young, asymptomatic, affected lamb are presented here, which demonstrate a progressive loss of the scotopic b-wave and unrecordable c-waves under halothane anesthesia. Even at this initial stage of disease, lesions were evident in the form of dystrophic retinal pigment epithelial (RPE) villi, and loss of photoreceptor cells and rod outer segments. Cone inner segments were enlarged and scanning electron microscopy emphasized these abnormalities. All cells in tapetal and nontapetal areas contained fluorescent inclusions with similar emission spectra (maximum = 539 nm). By transmission electron microscopy, storage bodies consisted of 'finger-print' profiles and were most prominent in bipolar cells. The pathological features of the retina correlate well with the observed ERG changes, reaffirming the sheep as a useful model to delineate early events in ceroid lipofuscinosis.

Animals↗