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M E Fitzgerald

Publications and source records attributed to M E Fitzgerald.

At least 37 records · Page 2Linked to original sources
PubMed1992

Vasoactive intestinal polypeptide-containing nerve fibers are increased in abundance in the choroid of dystrophic RCS rats.

As photoreceptor degeneration progresses in Royal College of Surgeons (RCS) rats, a variety of morphological and physiological alterations occur in the outer retina. Since the choriocapillaris responds to changes in the outer retina in other retinopathies, we examined the possibility that changes in the choroidal vasculature also occur in RCS rats. The choroidal and choriocapillary vessels in RCS and control (RCS-rdy+) rats were examined during the period after which photoreceptor loss and retinal vascular changes had occurred (7-mos to 28-mos). Light microscopic (LM) morphometry and electron microscopic (EM) examination showed no significant differences between these groups in the number, size or morphology of these vessels. However, EM image analysis revealed that nerve fibers and bundles were twice as abundant in the RCS choroid than in the control. Using immunohistochemical techniques at the LM level combined with image analysis we found that vasoactive intestinal polypeptide positive (VIP+) fibers were significantly increased in the RCS choroid compared with control choroid. In contrast, the abundance of immunoreactive fibers labelled for substance P and dopamine beta hydroxylase appeared similar in both the control and RCS choroid. Since VIP is a potent vasodilator, the increased abundance of nerve fibers in the RCS choroid in conjunction with the unaltered number and size of these vessels suggests that choroidal blood flow may be increased. It is uncertain whether this increase is a response to the outer retinal pathology or contributes to it.

Animals↗
PubMed1991

The choriocapillaris in spontaneously diabetic rats.

During diabetes in rats, the choroid of the eye shows increased permeability to albumin, basement membrane thickening, and decreased anionic charge sites on the abluminal surfaces of the choriocapillary microvessels. In other microvascular beds, permeability differences are correlated with differences in luminal membrane microdomains as indicated by the distribution of luminal membrane anionic charge. To see whether luminal surface charge distribution or other structural features of the choroidal microvasculature become altered during diabetes, we studied spontaneously diabetic and control rats using ultrastructural tracers and morphometric techniques. Rats were injected with horseradish peroxidase and perfused with aldehydes, and then retina-choroid tissue sections were incubated with cationized ferritin, reacted to visualize peroxidase, and prepared for electron microscopic study. The most striking alterations in the diabetic rats were vascular debris and migrating cells resembling vascular cells in the choriocapillaris stroma, suggesting an increase in capillary turnover. In addition, extracellular matrix material was increased, and peroxidase uptake and ferritin binding were low in some vessels of the diabetic rats compared with the controls. Variability was large in the diabetic animals, however, and other vessels remained apparently normal.

Animals↗
PubMed1991

Neurotransmitter organization of the nucleus of Edinger-Westphal and its projection to the avian ciliary ganglion.

Two morphologically distinct types of preganglionic endings are observed in the avian ciliary ganglion: boutonal and cap-like. Boutonal endings synapse on ciliary ganglion neurons (called choroidal neurons) innervating choroidal blood vessels, while cap-like endings synapse on ciliary ganglion neurons (called ciliary neurons) controlling the lens and pupil. Some of both types of preganglionic endings contain the neuropeptides substance P (SP) and/or leucine-enkephalin (LENK). Although both types of preganglionic terminals are also known to be cholinergic, there has been no direct evidence that SP and LENK are found in cholinergic endings in the ciliary ganglion. The present studies in pigeons, which involved the use of single- and double-label immunohistochemical techniques, were undertaken to examine this issue, as well as to (1) determine the relative percentages of the boutonal and cap-like endings that contain SP, LENK, or both SP and LENK; and (2) determine if the two different types of terminals in the ciliary ganglion arise from different subdivisions of the nucleus of Edinger-Westphal (EW). Single- and double-label immunohistochemical studies revealed that all neurons of EW, regardless of whether they contained immunohistochemically detectible amounts of SP or LENK, are cholinergic. In the medial subdivision of EW (EWM), which was found to contain approximately 700 neurons, 20.2% of these neurons were observed to contain both SP and LENK, while 11.6% were observed to contain SP only and 10.7% were observed to contain LENK only. In contrast, in lateral EW (EWL), which was found to contain approximately 500 neurons, 16.2% of the neurons were observed to contain both SP and LENK, while 19.2% of the neurons were observed to contain SP only and 12.6% were observed to contain LENK only. Retrograde-labeling studies involving horseradish peroxidase injections into the ciliary ganglion revealed that EW was the sole source of input to the ciliary ganglion and all, or nearly all, neurons in EW innervate the ciliary ganglion. Immunohistochemical labeling of the ciliary ganglion neurons with an antiserum against choline acetyltransferase revealed that approximately 900 choroidal neurons and approximately 600 ciliary neurons are present in the ganglion, all of which receive cholinergic preganglionic endings. Of the choroidal neurons, 94% receive butonal terminals containing both SP and LENK, while only 2% receive SP+ only boutonal endings and 2% receive LENK+ only butonal endings. Of the ciliary neurons, 25% receive cap-like endings containing both SP and LENK, 30% receive cap-like endings containing only SP and 3% receive cap-like endings containing only LENK.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

The retinal microvasculature of spontaneously diabetic BB rats: structure and luminal surface properties.

Endothelial cell permeability and luminal surface anionic sites were studied in the retinal microvasculature of spontaneously diabetic rats. Horseradish peroxidase (HRP) was used as a tracer of pinocytotic transport, and cationized ferritin (CF) was used as a marker of luminal surface anionic sites. Diabetic and control rats were injected with HRP, and their retinas were fixed. Retinal tissue sections were then incubated in CF, reacted to visualize HRP, and prepared for quantitative electron microscopic analysis. In both control and diabetic rats treated with serotonin and histamine antagonists to prevent HRP-induced vascular changes, the endothelium formed a barrier to the tracer. Pinocytotic uptake was relatively low in most vessels. Reaction product was restricted to pinocytotic vesicles, tubular cisternae, and multivesticular bodies. HRP uptake appeared high in some of the deep capillaries of the diabetic retinas as compared with that of the controls, but the difference was not statistically significant. HRP-induced transendothelial permeability was observed in both control and diabetic rats when serotonin and histamine antagonist pretreatment was omitted. CF studies showed anionic sites in four luminal surface microdomains in control and diabetic endothelial cells. CF-binding, anionic sites were present on the plasma membrane, on all coated vesicles, on some uncoated vesicles, and on most diaphragms of uncoated vesicles. Plasma membrane binding was sparse and patchy in some diabetic vessels, especially in the deep vessels of rats that were not treated with the serotonin and histamine antagonists. However, statistical analysis showed similar numbers of plasma membrane binding sites in diabetic and control rats pretreated with serotonin and histamine antagonists. Our data suggest that the retinal microvasculature in diabetic rats remains normal in terms of permeability and luminal membrane anionic charge.

Animals↗
PubMed1990

Evidence for retinal pathology following interruption of neural regulation of choroidal blood flow: Müller cells express GFAP following lesions of the nucleus of Edinger-Westphal in pigeons.

Choroidal blood flow in pigeons is regulated by the medial part of the nucleus of Edinger-Westphal (EW) via the ipsilateral ciliary ganglion. Interruption of this circuit by unilateral lesions of EW results in pathological modifications in the morphology of retinal photoreceptors in the ipsilateral eye in pigeons housed under 12hr light (400 lux)/12hr dark conditions. In the present study, we examined the effects of unilateral EW lesions on glial fibrillary acidic protein (GFAP) expression by retinal Müller cells in pigeons housed under the same lighting conditions. Since Müller cells in the retina of land vertebrates express increased GFAP during conditions of retinal pathology or stress (e.g. inflammation or hypoxia), this study would enable us to further evaluate the effects of disruption in the neural regulation of choroidal blood flow on the retina. We found that following EW lesions, retinal Müller cells expressed GFAP, with the precise intracellular location of the GFAP dependent on the amount of time elapsed following the lesion. One week after the EW lesions, GFAP labelling was restricted to the Müller cell endfeet in the nerve fiber layer and ganglion cell layer. By two-three weeks, the labelling had extended outward (or sclerad) into the portions of the Müller cells spanning the inner plexiform layer. Finally, by six weeks post-lesion, the entire extent of the Müller cell from the nerve fiber layer to the outer limiting membrane contained GFAP. No GFAP immunoreactivity in Müller cells was observed in the eyes contralateral to the EW lesions or in eyes in which the pupil had been fixed and dilated by lesions of the pretectal region. Our results suggest that the retina is in a state of physiological stress following interruption of the neural regulation of choroidal blood flow by EW lesions. Although the precise mechanisms by which altered choroidal blood flow regulation affects Müller cell GFAP production require elucidation, the results nonetheless highlight the importance of intact neural regulation of choroidal blood flow for retinal health.

Animals↗
PubMed1990

Control of choroidal blood flow by the nucleus of Edinger-Westphal in pigeons: a laser Doppler study.

Anatomical studies in birds have suggested that choroidal blood flow may be regulated by a circuit involving the following serially-connected components: the retina-the suprachiasmatic nucleus (SCN)-the medial subdivision of the nucleus of Edinger-Westphal (mEW)-the ciliary ganglion-the choroidal blood vessels. In order to better clarify the role of this circuit, we examined the effects of electrical stimulation of EW on choroidal blood flow in the ipsilateral eye, using laser Doppler velocimetry to monitor choroidal blood flow in the superior pole of the eye. Baseline choroidal blood flow values (144-311.3 mg/min per eye) were found to be comparable to those previously reported in rabbits, cats and primates. Stimulation of EW dramatically increased choroidal blood flow. The increases were current-related and the average maximal increases ranged between 300-700% above baseline values. In contrast, EW stimulation had little or no effect on overall bodily blood flow. All EW stimulation sites were later verified histologically. These results indicate that the SCN-mEW circuit in birds may be involved in mediating increases in choroidal blood flow, possibly in response to the levels of retinal illumination. Such adaptive neural regulation of choroidal blood flow may play an important role in mitigating the potentially deleterious effects of light on the retina.

Analysis of Variance↗
PubMed1989

Lectin-ferritin binding on spontaneously diabetic and control rat retinal microvasculature.

We previously reported, in the spontaneously diabetic Bio-Breeding (BB) rat, an increase in horseradish peroxidase (HRP) uptake that was associated with reduction and patching of cationized ferritin (CF) binding to anionic sites on the luminal plasma membrane of the retinal capillary endothelium. To see whether alterations in the negatively charged terminal sugar residues, N-acetyl-glucosamine (NAG) and sialic acid (SA), might contribute to these changes in the diabetic rat retina, we used lectin-ferritin (Fe) conjugates to study the distribution of these sugars on the retinal endothelial luminal membranes. Wheat germ agglutin (WGA, binds to NAG and SA) and Limax flavius (LFA, binds only SA) were used. Plasma membrane WGA-Fe binding was dense and uniform in control animals. Binding sites were also found in coated luminal vesicles, within some uncoated luminal vesicles and on their diaphragms. Unlabeled uncoated luminal vesicles were also seen, suggesting two populations of uncoated vesicles. In diabetic animals, the binding sites were present within the same membrane associated microdomains as in the controls. However, in the majority of outer plexiform layer (OPL) vessels in diabetic animals, WGA-Fe binding was reduced to a single, discontinuous layer of particles (p less than 0.02). In both diabetic and control vessels, WGA-Fe binding was greatly reduced by the addition of competitive sugars. A few particles remained on the plasma membrane, on the diaphragms of some vesicles, and at the edge of vesicles. LFA-Fe binding was similar to that seen with WGA-Fe in the presence of competitive sugars. These results suggest that luminal membranes of retinal capillaries are rich in NAG and contain little SA. The sparse WGA-Fe binding pattern in the diabetic OPL may reflect decreases in number or accessibility of NAG residues, since similar binding patterns are seen in both the control and diabetic animals under conditions specific for SA. Thus, alteration of terminal NAG residues may contribute to decreased luminal surface anionic sites and increased pinocytotic transport in the retinal microvasculature of spontaneously diabetic BB rats.

Acetylglucosamine↗
PubMed1989

Alterations in lectin binding accompany increased permeability in the dystrophic rat model for proliferative retinopathy.

In the dystrophic Royal College of Surgeons (RCS) rat, migration of vessels from the inner retina into the retinal pigment epithelium (RPE) is associated with neovascular proliferation and formation of vitreo-retinal membranes (VRMs), (Caldwell et al., 1988; Frank and Das, 1988). We studied permeability and luminal membrane glycoconjugates in these vessels using horseradish peroxidase (HRP) and lectin-ferritin (Fe) techniques. RCS and genetic control rats were injected with HRP, their retinas were fixed, incubated in Fe conjugates of wheat germ agglutinin (WGA-Fe) or concanavalin-A (ConA-Fe), reacted to demonstrate HRP, and prepared for electron microscopy. The RPE and VRM vessels in RCS retinas were compared with the normal inner retina and choriocapillaris vessels in RCS and genetic control rats. In both groups inner retinal vessels formed a barrier to HRP, while fenestrated choriocapillaris (CE) vessels were permeable to the tracer. In both of these vascular beds plasma membrane WGA-Fe binding was dense and uniform, while ConA-Fe binding was sparse and patchy. Studies with competitive sugars showed that WGA-Fe binding was primarily to N-acetylglucosamine (NAG) and that ConA-Fe was to mannose. In both RPE and VRM vessels tight junctions appeared intact, but both vessel types were permeable to HRP with the RPE vessels often containing fenestrae and channels. As compared with binding in the inner retina and CE vessels, WGA-Fe binding was lower in VRM vessels and normal in RPE vessels, while ConA-Fe binding was higher in both RPE and VRM vessels. Thus, increased permeability is accompanied by alterations in both NAG and mannose residues in the VRM vessels and with alterations in mannose residues and the presence of fenestrations and channels in the RPE vessels.

Animals↗
PubMed1982

Studies on the fine structure of the mitochondrial derivative in spermatozoa of a gastropod.

Spermatozoa of Limax sp. were studied by electron microscopy following thin section and freeze-fracture techniques. Mature spermatozoa were seen to be helically shaped, 150 microns long cells. A single mitochondrion extends the entire length of the spermatozoon. Its helical turn is the same as that of the spermatozoon. Freeze-fracture images of the spermatozoon reveal that the EF and PF, plasmalemmal faces contain scattered, 7-9 nm size particles, and that the PF, outer mitochondrial membrane face contains 8-10 nm size particles. The corresponding EF, outer mitochondrial face contains matching pits. A paracrystalline complex is situated between the inner and outer mitochondrial membranes. The complex is constructed of a series of 8-9 nm thick, 35 nm wide, helically orientated, tripartate elements which extend the full length of the spermatozoon. The helical tilt angle is approximately 55 degrees. Each element is composed of tightly approximated (interspace distance 10 nm), strands of particles 8-9 nm in diameter. Speculations as to the significance of this complex, and its location between inner and outer mitochondrial membranes are made. It is concluded that the paracrystalline order of the complex either reflects the molecular packing of enzyme systems present in the mitochondrion, or some other unknown function.

Animals↗
PubMed1981

Studies on membrane specializations in tentacular retractor muscle of the gastropod, Limax sp.

Retractor muscle cells of the optic tentacle of Limax sp. occur as a network beneath the epithelium. The cells are spindle-shaped, irregularly cross-striated, and they contain a large number of subsarcolemmal caveolae. Freeze-fracture images of the sarcoplasmic reticulum, caveolae and sarcolemma demonstrate distinct particulate organizations. Membranes of the sarcoplasmic reticulum contain typical 7-9 nm PF-face particles. The caveolae membranes contain linear, sometimes rhombic arrays of 12-15 nm EF-face particles. An extensive area of the sarcolemmal surface is occupied by caveolar invaginations. Other areas of the sarcolemma contain linear arrays of 7-9 nm PF-face particles and a few rhombic ordered, 7-9 nm PF-face particles. The results of the study are discussed relative to previous studies on particulate arrays in muscle membranes. It is concluded that these highly specialized sarcolemmal and caveolar particulate organizations may, in some way, reflect the large surface area changes which occur in these muscle cells.

Animals↗
PubMed1978

Primary sideroblastic anemia masked by bleeding.

A patient with characteristic features of iron deficiency was unexpectedly found to have circulating siderocytes. Bone marrow iron stain at this time showed absence of both hemosiderin and ringed sideroblasts; electron microscopy revealed absence of mitochondrial iron loading but presence of cytoplasmic ferritin in normoblasts. Replenishment of iron stores led to development of typical sideroblastic anemia. These observations suggest that increased percentage of siderocytes in otherwise typical iron deficiency anemia may signify the presence of a sideroblastic process masked by iron deficiency due to bleeding.

Aged↗
PubMedDate not supplied

Effect of choroidal and ciliary nerve transection on choroidal blood flow, retinal health, and ocular enlargement.

Our previous studies suggested that reduced choroidal blood flow (CBF) occurs with manipulations that yield myopic eye growth and that these reductions are primarily a consequence of the ocular enlargement. We could not entirely rule out the possibility, however, that reductions in CBF are at least to some extent antecedent and causal to the ocular enlargement. We therefore in the present study examined the effects on eye size of artificially reducing CBF by unilaterally transecting the choroidal nerves of the ciliary ganglion in four-day-old chicks. For comparison, we also transected the ciliary nerves in a second group of chicks or transected both ciliary and choroidal nerves in a third group of chicks. The effects of the nerve transections were evaluated in comparison to the effects of the orbital surgery itself (without nerve transection) in a fourth group termed the sham-operated control group. Two weeks after transection, CBF was measured using laser Doppler velocimetry, the ocular axial, nasotemporal and dorsoventral lengths were measured, and the eyes weighed. The results showed that CBF in birds with either choroidal nerve cuts or choroidal plus ciliary nerve cuts was greatly reduced in the treated eye (20-40% of nontreated eye). The treated eyes of these birds also showed gross depigmentation and histologically evident loss of the outer retina, most typically in the temporal retina. Birds with ciliary nerve cuts showed increased CBF in both eyes (131% right eye and 154% left eye compared to shams). Since ciliary nerve cuts yield fixed dilated pupils, increased CBF with ciliary nerve cuts appears consistent with the previously reported involvement of the choroidal nerves within a neural circuit subserving light-mediated upregulation of CBF. Clear effects on eye size were observed in the treated eyes in each group. The sham surgery alone yielded slight enlargement of the right eye compared to left eye, particularly in the axial dimension. In the choroidal nerve and the both nerve cut groups, nasotemporal and dorsoventral elongation were slightly diminished in the treated eyes compared to the sham-treated eyes. In contrast, enlargement of the right eye was slightly enhanced in the ciliary nerve cut group compared to the sham-treated eyes. The overall results suggest that large decreases in CBF do not enhance myopic eye growth, although large increases in CBF may.

Animals↗
PubMedDate not supplied

Central neural circuits for the light-mediated reflexive control of choroidal blood flow in the pigeon eye: a laser Doppler study.

Electrical stimulation in pigeons of the input from the medial subdivision of the nucleus of Edinger-Westphal (EWM) to the choroidal neurons of the ipsilateral ciliary ganglion, which themselves have input to the choroidal blood vessels of the ipsilateral eye, increases choroidal blood flow (ChBF). Since the EWM receives input from the contralateral suprachiasmatic nucleus (SCN), which in turn receives contralateral retinal input, the present study sought to determine if activation of the SCN by microstimulation or by retinal illumination of the contralateral eye would also yield increases in ChBF in that same eye. Using laser Doppler flowmetry (LDF) to measure ChBF, we found that electrical activation of the contralateral SCN by 100-Hz anodal pulse trains yielded increases in ChBF that were stimulus related and proportional to the stimulating current. These increases in ChBF elicited by the SCN stimulation were accompanied by increases in choroidal volume (vasodilation), but not by increases in systemic blood pressure. Furthermore, the increases could be blocked reversibly by lidocaine injection into the EWM. These results suggest that the increases in ChBF in the eye contralateral to the SCN stimulation were specifically mediated by the SCN-EWM pathway. Retinal illumination with a fiber optic light source was also found to increase ChBF in the illuminated eye, and these effects too could be blocked reversibly with lidocaine injection into the EWM or permanently by the EWM lesion. Control studies confirmed that the light-elicited increases were mediated by increases in choroidal volume (i.e. vasodilation), were not accompanied by systemic blood pressure increases, and were not artifactually generated by transocular illumination of the LDF probe. Thus, the SCN-EWM circuit may be involved in regulating ChBF in response to the level of retinal illumination and/or the visual patterns falling on the retina.

Analysis of Variance↗
PubMedDate not supplied

Functional and morphological assessment of age-related changes in the choroid and outer retina in pigeons.

We sought to determine if choroidal and outer retinal deterioration occur with age in pigeons, as they do in other species, and investigated the relationship between age-related retinal and choroidal changes. In 64 pigeons ranging in age over the pigeon lifespan (0.5-20 years), we measured some or all among the following parameters: choroidal blood flow (ChBF) by laser Doppler flowmetry, choroidal thickness and choriocapillary vessel abundance by LM histology, choriocapillary endothelial cell transport specializations by EM histology, acuity by behavioral methods, and degenerating photoreceptor abundance and total photoreceptor abundance by LM histology. Regression and Receiver Operator Curve (ROC) analyses were used to characterize the pattern of age-related changes and determine the ages at or by which significant changes occurred. For the 45 birds for which we measured choroidal parameters, choriocapillary vessel abundance showed a curvilinear decline with age and half of this decline occurred by 3.5-4.6 years. The endothelial cell transport specializations called channels also declined curvilinearly with age. Choroidal thickness was slightly increased between the ages of 3-6 years, and thereafter declined steadily so that choroidal thickness in the oldest birds was half that in the youngest. ChBF showed an abrupt decline of about 20% at 4 years and a further 20% decline thereafter. In the 53 birds for which we obtained visual acuity and/or photoreceptor data, we observed a curvilinear decline in acuity (with half the decline having occurred by 8 years) and a prominent stepwise decline of about 20% in photoreceptor abundance at 4.7 years, followed by further decline thereafter. The period of major photoreceptor loss coincided with ages during which about 10% of photoreceptors appeared to show degenerative changes (4-8 years of age). Using partial correlation analysis with the common effect of age held constant, ChBF was found to have a positive correlation with acuity. Our results show that ChBF and choroidal vascularity decline significantly with age in pigeons, as do acuity and photoreceptor abundance. Our statistical analyses suggest that prominent choroidal vascular decline preceded the visual decline, and that there is a positive relationship between choroidal and visual functions. Thus, our findings are consistent with the view that age-related decline in choroidal function might contribute to age-related vision loss in pigeons.

Aging↗