William W. Dawson

A primate model for age related macular drusen.

A closed colony of semi-free-ranging rhesus monkeys maintained in isolation since 1938 by the Caribbean Primate Research Center (CPRC) is being studied as a model for age related macular drusen. Of examined colony animals 57.7% of the monkeys and 47.3% of their eyes have drusen. The prevalence and severity of drusen are linearly related to increasing age and are significantly higher in specific maternal lineages (matrilines). An electrophysiological estimate indicates loss of function associated with drusen. Prevalence of drusen in CPRC females is almost twice that of males, while the prevalence among CPRC animals in general appears to be several times that of monkeys from continental US facilities. Evidence suggests that the frequency of endstage lesions is also similar to that in human populations. The CPRC matriline monkeys appear to provide the best model yet reported for human age related macular drusen.

Pattern evoked retinal response (PERR) in human: effects of spatial frequency, temporal frequency, luminance and defocus.

Spatial and temporal tuning were examined for both retinal and cortical signals using low contrast sinusoidol gratings. Maximum PERR and VECP responses occurred at the 4 Hz alternation rate and at 0.68 and 2.2 cpd, respectively. A 25% low spatial frequency attenuation (LSFA) was observed for the PERR. To test the possibility that prior inability to detect LSFA of the PERR was due to the masking of a pattern contrast response by a large amplitude local luminance response, mean luminance and optical power were varied in separate experiments. Greater relative LSFA was observed with a lower mean luminance and defocus differentially affected responses elicited by high and low spatial frequency gratings. In addition greater relative LSFA was observed when power at the second harmonic rather than amplitude was the dependent measure. We conclude that LSFA may be observed. The absence of spatial tuning in previous reports is explained by the masking of pattern contrast by local lumnance responses. Detection of LSFA in the present experiments is attributed to use of stimulus conditions which minimize local luminance responses and the use of an objective response measure with a high signal-to-noise ratio, i.e., power at the second harmonic of the stimulation frequency.

Hereditary retinal degeneration in the Rhode Island Red chicken. I. Histology and ERG

Hereditary blindness in Rhode Island Red chickens was analyzed at various post-hatching stages by light microscopy and electrophysiological recordings. At the time of hatching the retina of affected chicks appeared morphologically normal and identical to that of control, non-affected chicks. Whereas the electroretinographic (ERG) response to light stimulus in normal chicks was near the adult level at the time of hatching, no ERG either under light- or dark-adapted conditions was measurable in affected chicks at any stage examined. Photoreceptor cells of affected animals were seen to undergo degenerative changes after about one week post-hatching. Decrease in number of outer segments, spaces between inner segments and large spaces in the outer nuclear layer were apparent by Day 10. By Day 21, most of the photoreceptor inner segments appeared swollen, and the decrease in number of outer segments and photoreceptor nuclei was noteworthy. By the end of the second month no outer segments were seen and the majority of identifiable inner segments were from cones, a larger proportion than normally present being double cones. By six months, very few photoreceptor inner segments and nuclei remained; most inner segments were deformed and diminutive but usually contained a clearstaining oil droplet characteristic of the principal member of the double cone. In all stages after one week of age, pycnotic nuclei and thinning of inner retinal layers accompanied photoreceptor degeneration. In all specimens examined, degeneration of retinal cells was more pronounced in the superior central retina than in the periphery. Pathological changes were frequently also noted in the pigment epithelium overlying degenerating retina. Because the chick retina is well developed at birth, contains a fovea and a significant cone population and because cones (particularly one specific type) survive rods, we believe that this congenitally-blind chicken may be a useful model for studies on human hereditary retinal degenerations.

Non-Diabetic Retinal Abnormalities in Chronic Pancreatitis

To determine whether retinal abnormalities occur in patients with chronic pancreatitis, ophthalmoscopic and retinal-function evaluation was performed in 28 patients with chronic pancreatitis and 19 healthy subjects. The final threshold of dark adaptation was significantly increased 40 per cent (P less than 0.001) in patients with pancreatitis, whether or not they had steatorrhea. Patients with steatorrhea had a significant decrease of about 42 per cent (P less than 0.001) in the b-wave of the electroretinogram, a measure of both rod and cone function. Seven of the 28 patients complained of difficulty with hight vision; six of these seven had morphologic lesions on ophthalmoscopic examination, confirmed by fluorescein angiography. No correlation was found between any of the retinal abnormalities and the serum vitamin A or zinc levels or glucose tolerance. Non-diabetic retinal lesions and retinal-function abnormalities are common in patients with chronic pancreatitis, even in the absence of steatorrhea.

The histology of retinas from the pinnipedia

Abstract The cellular components, receptors, bipolar and ganglion cells of retinas from several species of pinnipeds (seals and sea lions) were quantified. No area centralis was seen in any specimen. Only rod shaped receptors were observed. Ratios of these receptors to ganglion cells were determined and found to be similar to estimates of human parafoveal receptor to ganglion cell ratios. These histologically determined ratios support the behaviorally tested acuity in these animals.

Unusual Retinal Cells in the Dolphin Eye

By comparison to the cellular constituents of the retinas of certain other diving mammals, the elements of the dolphin retina include an unusually large number of specialized cells. Both cone and rod receptors may be identified. An unusual amacrine cell may be seen which produces a process that spans the cells between the inner plexiform and outer plexiform layers. Most unusual is a layer of giant ganglion cells which appears to serve most of the central retina. The giant ganglion cells support giant dendrites and optic nerve fibers which range up to 8 micrometers in diameter.

Corneal thickness and endothelial cell density measured by non-contact specular microscopy and pachymetry in Rhesus macaques (Macaca mulatta) with laser-induced ocular hypertension

PURPOSE Sustained increase in intraocular pressure (IOP) in humans results in a loss of corneal endothelial cells and an increase of corneal thickness. The effects of chronically elevated IOP on the corneal endothelium of monkeys with laser-induced ocular hypertension, a commonly used animal model of human glaucoma have not been documented. This study examined the central corneal thickness (CCT), the corneal endothelial cell density (ECD), and the corneal endothelial cell size (ACS) in Rhesus monkeys with experimental ocular hypertension. Materials and methods. Ten male monkeys with argon laser-induced ocular hypertension in one eye for an average duration of 2.4+/-0.7 years, were sedated with ketamine hydrochloride, and the CCT, ECD, and ACS measured at the center of the cornea of both eyes with a Topcon SP-2000P non-contact specular microscope (Topcon America Corporation((R)), Paramus, NJ, USA). CCT was also measured using a DHG-500 Pachette ultrasonic pachymeter (DHG Technology Inc., Exton, PA, USA). Mean and standard deviation (S.D.) of CCT, ECD and ACS for each eye was calculated and statistically compared.Results. Mean CCT in the hypertensive and normal eyes measured by specular microscopy was 0.477+/-0.023mm and 0.468+/-0.020 mm, respectively. Mean ECD in the hypertensive and normal eyes was 2601.7+/-631.8 and 3990.2+/-402.9 cells mm(-2), respectively. The mean size of the endothelial cells was 252.4+/-23.9 micro m(2) in the normal eye and 408.7+/-115.0 microm m(2) in the hypertensive eye. No significant difference in the measurement of CCT was observed between the specular microscope and the pachymeter (p=0.46). No significant difference in the mean CCT was observed between the two eyes (p=0.4820), whereas the mean ECD was significantly lower in the hypertensive eye than in the normal eye (p<0.001). The ECD was inversely related to the length of IOP elevation (p<0.001). CONCLUSIONS No difference in the corneal thickness measurement was observed between the specular microscopy and the pachymetry techniques. Chronic ocular hypertension did not significantly affect the CCT, but caused a significant loss of endothelial cells in the center of the cornea of the laser treated eyes compared to the normotensive eyes. The duration of elevated IOP was the most important factor affecting the ECD.

Primary open angle glaucomas in the rhesus monkey.

Rhesus monkeys from the closed Cayo Santiago colony of the University of Puerto Rico demonstrate elevated (> or = 22 mm Hg) intraocular pressure in a pattern which significantly favours certain maternal lineage groupings. The colony had remained genetically pure since 1938. Of nine matriarchal lineages (matrilines) examined, two had an incidence of ocular hypertension of more than 40% and six of more than 10%. Information on 18 matrilines is currently located in the colony data base which identifies each individual and its vital statistics. In 1990, six animals were moved to the laboratory in Florida. Among those from a low incidence matriline, we found abnormal optic nerve cups, pallor, reduced function of (mainly peripheral) fields, progression and loss of optic nerve axons in the presence of ocular hypertension. In another individual where the cup/disc ratio for the right eye was 0.7 and left eye 0.4 and outflow facility was normal, we excluded all other causes of optic nerve atrophy, and low tension glaucoma was diagnosed. This female was from a matriline with a low incidence of ocular hypertension. Relatively rapid aging (3-4 years/human year) monkeys with ocular hypertension and familial clustering produce a near ideal glaucoma research model.

Diurnal Intraocular Pressure Curves in Healthy Rhesus Macaques (Macaca mulatta) and Rhesus Macaques With Normotensive and Hypertensive Primary Open-Angle Glaucoma

PURPOSE The authors identify any diurnal intraocular pressure (IOP) variation in healthy Cayo Santiago macaques, as well as Cayo Santiago macaques with normotensive and hypertensive primary open-angle glaucoma (POAG), to further evaluate their potential value as a model for human POAG. METHODS Twenty-four monkeys (eight animals each of the healthy control, normotensive glaucoma, and hypertensive glaucoma groups) were sedated with ketamine hydrochloride and the IOP measured hourly from 8:00 AM until 3:00 PM with a Tonopen XL applanation tonometer (Mentor, Norwell, MA, U.S.A.). Mean IOP time profiles, mean IOPs at each observation time, and linear trends in mean IOP over time were compared among groups. Intraocular pressure rate-of-change over time and residual variation about the regression line for each individual eye were analyzed. Cup/disc ratio (C/D) was compared with baseline IOP, IOP profile mean and slope, and IOP residual variation. RESULTS A significant group and time effect on mean IOP (p = 0.0001 and 0.011, respectively), with highest values at 2:00 PM or 3:00 PM, and a significant increasing linear trend in mean IOP over time in the hypertensive group were observed (p = 0.012). Intermediate readings between control and hypertensive mean IOPs were identified for the normotensive glaucoma group. The biggest range of IOP variation was found in the hypertensive glaucoma monkeys. Higher variations in IOP did not lead to an increase in C/D. CONCLUSIONS This study provides evidence that the Cayo Santiago macaques are a valuable model for human normotensive and hypertensive POAG.

Phase distortion of biological signals: Extraction of signal from noise without phase error☆

Abstract Analog filtering can produce distortion of signals by shifting phase. The signal-to-noise ratio achieved by averaging a small number of signals buried in noise will be improved greatly if that signal ensemble is averaged upon itself so that the time of signal onset varies over a predetermined series of intervals (interference filtering). The result of interference filtering is similar to the one obtained by sharp bandpass filtering, but provides zero phase shift. Transfer functions were constructed for first, second and third order interference filters. Effectiveness of interference filtering is demonstrated with synthesized signals and biological data. Distortion of signal shape and time characteristics were demonstrated in biological data where signal-to-noise ratio had been improved by analog frequency filtering.