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D S McLeod

Publications and source records attributed to D S McLeod.

12 recordsLinked to original sources
PubMed1992

A new technique for visualization of the human retinal vasculature.

Adenosine diphosphatase, an endothelial cell ectoenzyme that hydrolyses adenosine 5'-diphosphate to adenosine monophosphate, has been used histochemically to study the human retinal vasculature in flat mounts or as flat-embedded tissue that can be sectioned. In all retinas, reaction product was confined almost exclusively to the vasculature, with arteries having more reaction product than veins or capillaries. Adenosine diphosphatase activity was observed in endothelium, smooth-muscle cells, pericytes, and erythrocytes. In the more elaborate version of the technique, the adenosine diphosphatase-incubated retinas were flat embedded in glycol methacrylate. This allowed study of the retinal vasculature in dual perspective: en bloc with the use of dark-field microscopy and specific areas of interest histologically sectioned for further evaluation. The technique is simple and preserves angioarchitecture because the retinas are intact, and patency of the vasculature can be determined.

Adult↗
PubMed1992

Increased sensitivity of the non-human primate eye to microwave radiation following ophthalmic drug pretreatment.

Previous studies in our laboratory have established that pulsed microwaves at 2.45 GHz and 10 mW/cm2 are associated with production of corneal endothelial lesions and with disruption of the blood-aqueous barrier in the non-human primate eye. In the study reported here we examined ocular damage in monkeys (M. mulatta and M. fascicularis) following topical treatment with one of two ophthalmic drugs (timolol maleate and pilocarpine) that preceded exposure to pulsed microwaves. Anesthetized monkeys were sham exposed or exposed to pulsed, 2.45 GHz microwaves (10 microseconds, 100 pps) at average power densities of 0.2, 1, 5, 10, or 15 mW/cm2 4 h a day for 3 consecutive days (respective SARs were 0.052, 0.26, 1.3, 2.6, and 3.9 W/kg). Immediately before microwave exposure, one or both eyes were treated topically with one drop of 0.5% timolol maleate or of 2% pilocarpine. Following administration of a drug, we observed a significant reduction in the power-density threshold (from 10 to 1 mW/cm2) for induction of corneal endothelial lesions and for increased vascular permeability of the iris. Diagnostic procedures (in vivo specular microscopy and fluorescein iris angiography) were performed following each exposure protocol. In addition, increased vascular permeability was confirmed with horseradish peroxidase tracer techniques. Although we did not measure intraocular temperatures in experimental animals, the results suggest that a mechanism other than significant heating of the eye is involved. Our data indicate that pulsed microwaves at an average SAR of 0.26 W/kg, if administered after pretreatment with ophthalmic drugs, can produce significant ocular effects in the anesthetized primate.

Administration, Topical↗
PubMed1991

Immunohistochemical localization of transforming growth factor-beta in human photoreceptors.

Transforming growth factor-beta (TGF-beta) is a multifunctional growth factor that can either stimulate or inhibit cellular proliferation depending on cell type and culture conditions. The immunohistochemical localization of TGF-beta was investigated in human retinas and choroids using streptavidin peroxidase immunohistochemistry and a polyclonal rabbit antibody directed against the N-terminal 30 amino acids of TGF-beta 1. This antibody recognizes the beta 1 form of TGF-beta but not beta 2. TGF-beta localization was observed exclusively in photoreceptors in all adult non-diabetic and non-insulin dependent diabetic eyes, and 4 of 6 insulin dependent eyes. It was determined that TGF-beta was associated with both rods and cones using localization of peanut agglutinin (PNA), a lectin which binds to cone sheaths, on serial sections. Chondroitinase ABC digestion of sections prior to immunohistochemistry did not reduce TGF-beta immunoreactivity, suggesting that binding was not to glycosaminoglycans in the interphotoreceptor matrix. TGF-beta immunoreactivity was not observed in 2 premature human eyes in which photoreceptor outer segments had not yet developed. Localization in photoreceptors was also not observed in photocoagulation scars, in atrophic regions in a diabetic retina, nor in detached areas of retina from a young victim of head trauma. Based on PNA binding, succinate dehydrogenase enzyme histochemistry and phase contrast microscopy on adjacent sections, the TGF-beta negative areas of these retinas did not appear to have viable photoreceptors. This work demonstrates that TGF-beta is found exclusively in viable adult human retinal photoreceptors. It's function in these cells is currently not known.

Adult↗
PubMed1991

Immunolocalization of tissue plasminogen activator in the diabetic and nondiabetic retina and choroid.

Retinal capillary closure is a common finding in many patients with diabetic retinopathy. The cause of this capillary occlusion is unknown. Since occlusions in microthromboembolic disease can occur because of deficiencies in tissue plasminogen activator (tPA) and since systemic tPA decreases with an increasing duration of diabetes mellitus, the immunohistochemical localization of tPA in the retinas and choroids of diabetic and nondiabetic patients was investigated. The localization of tPA was confined to arteries and arterioles in peripheral retinas from nondiabetics. Both veins and arteries were positive in these choroids. Two of three noninsulin-dependent diabetics had normal levels of immunoreactivity in their retinas, and all had normal levels of immunolocalization in their choroids. All but 2 of the 12 insulin-dependent diabetic eyes (IDDM), however, had reduced levels of retinal tPA immunoreactivity which was most pronounced in their peripheral retinas. Seven eyes from patients with IDDM had no reaction product in their peripheral retinas. Two such eyes also had reduced tPA immunoreactivity in their choroidal vessels. Some tPA-positive vessels were observed in the central retinas of these eyes, but the number of positive vessels and amount of reaction product was greatly reduced compared with eyes from nondiabetic patients. These observations suggest that IDDM patients have reduced fibrinolytic activity in their retinas, which might predispose them to thromboembolic disease.

Adult↗
PubMed1989

Localization of basic fibroblast growth factor to the developing capillaries of the bovine retina.

The basic fibroblast growth factor (FGF) is a potent mitogen that has vascular endothelium as one of its principle target cells. Recent work has provided both the complete amino acid sequence of basic FGF and the nucleotide sequence of the genes for both human and bovine basic FGF. Although capillary endothelial cells have been shown to produce basic FGF in vitro and to deposit basic FGF in their extracellular matrix in vitro as well, no direct evidence yet exists for the distribution of basic FGF in vivo. Antipeptide antibodies were prepared against a 15-amino-acid sequence from the amino terminus of basic FGF in order to avoid cross-reactivity with acidic FGF, a protein with 55% overall homology to basic FGF. After affinity purification, these antisera were used to localize the basic fibroblast growth factor in the fetal and adult bovine retina. Immunoreactive material was found in capillaries of the inner nuclear layer, a capillary network undergoing development during the third trimester in the fetal bovine eye. Although the resolution of the technique does not permit a unique assignment of cellular localization, the presence of stain immediately adjacent to the lumen of capillaries suggests that capillary endothelial cells may produce the basic fibroblast growth factor in vivo during vascular development.

Amino Acid Sequence↗
PubMed1987

Visualization of a developing vasculature.

The events involved in vasculogenesis still remain obscure. One difficulty has been the techniques employed to visualize angioblasts, i.e., vascular precursors, during the genesis of blood vessels. The retina provides a unique model for studying these events since it is not completely vascularized in some mammals at birth. Using a previously published magnesium-dependent ATPase technique to visualize the developing retinal vasculature and its precursors, and embedding this tissue in JB-4 methacrylate for serial sectioning, has permitted examination of the retinal vasculogenic processes in dual perspective. The technique has permitted observation of the stages in angioblast differentiation and the apparent importance of glycosaminoglycan-rich cell-free spaces in this process. Perhaps the most important observation is that initial vessel formation occurs by coalescence of angioblasts after differentiation in situ.

Adenosine Triphosphatases↗
PubMed1985

Postnatal retinal vascular development of the puppy.

Retinal vascular development during the first three postnatal weeks was studied in 63 purebred beagle puppies. Use of a positive enzyme histochemical reaction for adenosine triphosphatase in the nuclei and nucleoli of vascular cells made visualization of the retinal vasculature possible. Animals were killed by decapitation. Thus, artifacts resulting from use of anesthetics or tracer substances were avoided. In general, this study demonstrates important similarities between canine and human retinal vascular development, and this gives further reason to use of the puppy retina as a superior model for studying retrolental fibroplasia pathogenesis. This staining technique demonstrates undifferentiated cells in the avascular retina that appear to be vascular precursors or angioblasts. Primordial vessels form by organization of differentiating angioblasts that exist in peripheral retinal cystic spaces at birth, or by addition of fully differentiated endothelium; they form unlike neovascularization. Müller cell processes appear to provide a structural matrix throughout the avascular puppy retina on which differentiated angioblasts organize into a vascular network. Arteries develop in beds of primordial capillaries lying near the leading edge of the developing vasculature. This precedes vein formation which occurs through a process involving coalescence of embryonic capillaries which themselves were derived from primordial capillaries. Preliminary examination of eight mongrel kitten retinas prepared by this method clearly indicates that the puppy retina is much more completely vascularized at birth than that of the newborn kitten. Moreover, the rate of postnatal retinal vascularization is significantly faster in the kitten. The kitten vasculature does appear to form by the organization of angioblasts as in the puppy, but kitten angioblasts have a different appearance from those in the puppy.

Adenosine Triphosphatases↗
PubMed1984

Prostaglandins as mediators of vasotonia in the immature retina.

In vivo observations of the immature beagle puppy retina indicates that in general O2-breathing induces vasoconstriction whereas CO2 or CO2 combined with O2 induces vasodilation. It was the goal of this study to determine whether a specific correlation could be found between this pattern of vascular response to changes in blood gas content and production of prostaglandins in the eye. Prostaglandin production by puppy choroidal and retinal tissues and platelets exposed in vitro to these gas combinations was such that it appears platelet-derived thromboxane could have a significant influence in determining retinal vasotonia.

Animals↗
PubMed1980

The mechanism of optic nerve damage in experimental acute intraocular pressure elevation.

We produced intraocular pressure (IOP) elevations in 32 primate eyes and studied retinal ganglion cell rapid axonal transport with autoradiography and electron microscopy. Animals breathing room air at sea level pressure were compared to animals breathing 100% oxygen at 3 atm pressure in a hyperbaric chamber. Despite major increases in arterial oxygen levels in the hyperbarically oxygenated animals, both groups had axonal transport blockade at the optic nerve head. Anoxia appears not to be the most important cause of acute axonal damage induced by elevated IOP. The pattern of axonal abnormality within individual fiber bundles at the optic nerve head provides support for mechanical compression as a more likely alternative cause for induced neural damage.

Animals↗
PubMed1978

The effect of blood on ocular fundus reflectance and determination of some optical properties of retinal blood vessels.

Light reflected from 50 micrometer diameter spots on the fundi of two adult rhesus monkeys was measured as a function of wavelength in 10 nm jumps from 400 to 900 nm. The areas measured were a retinal artery and vein, areas of the disk, macula, and retina devoid of visible blood vessels, and the foveola. The eyes of the two monkeys were then exsanguinated, the blood vessels were filled with normal saline, and reflectances of the same spots on the fundi were again measured. The pairs of reflectance curves were compared and demonstrated that blood is not the major determinant of the characteristic shapes of the retinal tissue spectral reflectance curves. From the pre-exsanguination and postexsanguination data, the isolated retinal artery and vein wall reflectances were determined to be 0.020 and 0.009, respectively, their transmittances 0.837 and 0,977, and the fractions of light absorbed by them 0.143 and 0.014, respectively, in the visible spectral region below 500 nm.

Animals↗
PubMed1977

Reflection of light by small areas of the ocular fundus.

Light reflected from 50 micrometer spots on the fundi of two rhesus monkeys and three human volunteers was measured as a function of wavelength in 10 nm. jumps from 400 to 900 nm. The areas measured were a retinal artery and vein, areas of the disk, macula, and retina devoid of visible blood vessels, and the fovea.

Adult↗