Search PubMed⌕ Search

Biomedical subjects

R W Beuerman

Publications and source records attributed to R W Beuerman.

At least 37 records · Page 2Linked to original sources
PubMed1998

A unified theory of the role of the ocular surface in dry eye.

It is our belief that the pathology of dry eye occurs when systemic androgen levels fall below the threshold necessary for support of secretory function and generation of an anti-inflammatory environment (Fig. 3). When this occurs, both the lacrimal gland and the ocular surface become irritated and inflamed, and they secrete cytokines that interfere with the normal neural connections that drive the tearing reflex. This leaves the lacrimal gland in an isolated condition, perhaps exacerbating atrophic alterations of the glandular tissue. These changes allow for antigen presentation at the surface of the lacrimal acinar cells and increase lymphocytic infiltration of the gland. A similar series of events may be occurring on the ocular surface. From this hypothesis we conclude: 1. The ocular surface, lacrimal gland, and interconnecting innervation act as an integrated servo-mechanism. 2. Once the lacrimal gland loses its androgen support, it is subject to immune/neurally mediated dysfunction. 3. The ocular surface is an appropriate target for dry eye therapeutics.

Animals↗
PubMed1998

Interface inflammation after laser in situ keratomileusis. Sands of the Sahara syndrome.

PURPOSE: To determine the source of the interface debris that causes the interface inflammation known as "sands of the Sahara" after laser in situ keratomileusis (LASIK). SETTING: Department of Ophthalmology, LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans, USA. METHODS: A microkeratome (Automated Corneal Shaper) was used to make a LASIK flap in 8 eyes of 4 rabbits. In 4 eyes, the blade was used directly from the sterile pack; in the contralateral 4 eyes, the blade was cleaned prior to use. In vivo confocal microscopy of the corneas was performed 1 day after surgery. An unused, cleaned blade and an unused, uncleaned blade, as well as blades used in the rabbit eyes, were examined by scanning electron microscopy. RESULTS: Confocal microscopy revealed numerous fragments of debris surrounded by inflammatory cells in the LASIK flap interfaces created by blades taken directly from the sterile package. Interfaces created by the cleaned blades showed only rare, scattered bits of debris. Scanning electron microscopy of the unused blades showed debris on the uncleaned blade removed directly from the sterile package. CONCLUSION: Post-LASIK interface inflammation may be caused by debris on the microkeratome blade, although other sources are possible. The interface debris and inflammation can be reduced or eliminated by cleaning the microkeratome blade before use.

Animals↗
PubMed1998

Effect of sensory denervation on the structure and physiologic responsiveness of rabbit lacrimal gland.

PURPOSE: This work was conducted to determine the effects of unilateral trigeminal ganglion ablation on lacrimal gland structure and secretory activity. METHODS: Adult male New Zealand rabbits underwent unilateral thermocoagulation of the ophthalmic division of the trigeminal ganglion. Sensory denervation was affirmed by anatomic inspection of the lesion and transmission electron microscopy (TEM) of the lacrimal gland innervation. Eight to 10 days after the procedure, the intraorbital lacrimal glands were removed from both sides. To compare the physiologic competence of the intact and denervated glands, freshly isolated gland fragments from the paired intact and denervated glands were stimulated with carbachol (100 microM), isoproterenol (10 microM), phorbol-12,13-dibutyrate (PDBu, 10 microM), forskolin (40 microM), or vehicle. Total secreted protein was measured at 30 or 60 min after the establishment of baseline values. Intact and denervated glands also were examined by light and TEM, and the morphologic appearance of the acinar structures as well as the appearance of nerves innervating the gland after denervation were assessed. Similar experiments were conducted with animals that underwent unilateral superior cervical ganglionectomy. RESULTS: Tissues from sensory denervated glands released significantly more protein than did tissues from innervated glands in response to in vitro stimulation by carbachol or isoproterenol but not in response to PDBu or forskolin. Microscopy showed that the acinar cells that had undergone sensory denervation showed a massive accumulation of secretory granules. The secretory granules filled the entire cytoplasmic space and displaced the ellipsoidal nuclei to the extreme periphery. Examination of segments of nerves revealed numerous unmyelinated axons, a few small-diameter myelinated axons, and a large amount of nerve degeneration after sensory denervation. In contrast to the effects of sensory denervation, sympathetic denervation did not alter either the acinar appearance or secretory responsiveness of the gland. CONCLUSION: Loss of the considerable sensory innervation from the trigeminal ganglion has pronounced effects on the pharmacologic responsiveness and the structure of the lacrimal gland. The effects of sensory innervation on the gland may be mediated through two possible pathways: direct input to the gland or control of the preganglionic parasympathetic pathway.

Animals↗
PubMed1998

The pathology of dry eye: the interaction between the ocular surface and lacrimal glands.

BACKGROUND: Most dry-eye symptoms result from an abnormal, nonlubricative ocular surface that increases shear forces under the eyelids and diminishes the ability of the ocular surface to respond to environmental challenges. This ocular-surface dysfunction may result from immunocompromise due to systemic autoimmune disease or may occur locally from a decrease in systemic androgen support to the lacrimal gland as seen in aging, most frequently in the menopausal female. HYPOTHESIS: Components of the ocular surface (cornea, conjunctiva, accessory lacrimal glands, and meibomian glands), the main lacrimal gland, and interconnecting innervation act as a functional unit. When one portion is compromised, normal lacrimal support of the ocular surface is impaired. Resulting immune-based inflammation can lead to lacrimal gland and neural dysfunction. This progression yields the OS symptoms associated with dry eye. THERAPY: Restoration of lacrimal function involves resolution of lymphocytic activation and inflammation. This has been demonstrated in the MRL/lpr mouse using systemic androgens or cyclosporine and in the dry-eye dog using topical cyclosporine. The efficacy of cyclosporine may be due to its immunomodulatory and antiinflammatory (phosphatase inhibitory capability) functions on the ocular surface, resulting in a normalization of nerve traffic. CONCLUSION: Although the etiologies of dry eye are varied, common to all ocular-surface disease is an underlying cytokine/receptor-mediated inflammatory process. By treating this process, it may be possible to normalize the ocular surface/lacrimal neural reflex and facilitate ocular surface healing.

Animals↗
PubMed1998

In vivo confocal imaging of corneal neovascularization.

PURPOSE: To investigate the cellular dynamics of vessel formation during corneal neovascularization in the living eye by confocal microscopy. METHODS: Corneal neovascularization was initiated by placing a 7-0 silk suture through the corneal stroma 3 mm from the limbus at the 12 o'clock position in both eyes of 10 New Zealand white rabbits. The corneas were examined for vessel ingrowth at intervals from 1 to 15 days after suture placement using a tandem scanning confocal microscope with a 20X water immersion objective, as well as a slit-lamp biomicroscope. Changes in the limbal vessels were recorded on videotape for later analysis. As early vessel growth appeared to be associated with corneal nerves, the total number of sprouts and the number of sprouts along nerves were counted in confocal images, and the results analyzed for statistical significance. Vessel growth and the structural relationship between vascular buds and the deep stromal nerves were examined by light and transmission electron microscopy. RESULTS: The early events of cell migration from the limbal microvessels were found to be associated with the deep stromal nerves; although this association was easily visualized by confocal microscopy, it could not be documented by slit-lamp biomicroscopy. By 18 h after suture placement, the limbal vessels were dilated and the first vascular buds appeared as short, pointed, or flat-topped protrusions from the deep limbal capillaries. By 96 h, the capillary buds had increased in density and had begun to form lumens. Movement of red blood cells was established between 72 and 80 h after the first signs of bud formation, at the same time that cells of immune origin were seen. Confocal microscopy revealed and transmission electron microscopy verified that new bud formation began with the formation of vascular tubes by endothelial migration along the deep stromal nerves. The total number of sprouts and the number of sprouts associated with stromal nerves were similar on days 1 and 2 but differed on days 3-7, suggesting an association between sprouts and nerves in the early stages of neovascularization. CONCLUSION: Using real-time white light confocal microscopy, we were able, for the first time, to observe the process of corneal neovascularization in the living eye, from the earliest stages within hours after initiation to 2 weeks. The deep stromal nerves appear to serve as a focus for the growth of new vessels, by attracting and supporting vessel growth and/or by providing a potential space for movement of the endothelial cells. Confocal microscopy may provide a new approach to achieving a better understanding of the mechanisms involved in corneal neovascularization.

Animals↗
PubMed1998

Characterization of fibrous retrocorneal membrane by confocal microscopy.

PURPOSE: To study the appearance of a fibrous retrocorneal membrane as seen by confocal microscopy. METHODS: A 67-year-old white woman with a history of multiple ocular surgeries, including repeated penetrating keratoplasties for aphakic bullous keratopathy, developed a retrocorneal membrane in the right eye. The membrane was first noticed 3 years after the last corneal transplant and remained stable subsequently. The patient was examined by in vivo white light tandem-scanning confocal microscopy. RESULTS: At the level of the retrocorneal membrane, confocal microscopy disclosed the presence of a hyperreflective fibrous-appearing layer. Normal endothelial cells could not be found. Anterior to the hyperreflective layer, activated keratocytes were identified. CONCLUSION: Confocal microscopy may allow noninvasive diagnosis of fibrous retrocorneal membrane. Additionally, our data suggest that the posterior keratocytes might play a role in the production and deposition of fibrous tissue.

Aged↗
PubMed1998

Expression of c-Fos protein in the spinal cord after brachial plexus injury: comparison of root avulsion and distal nerve transection.

OBJECTIVE: Clinical reports indicate poor outcomes for avulsion injuries, compared with more peripheral nerve damage. These two different injuries may both affect gene expression in spinal neurons, and the changes in gene expression may be related to the types of injuries. METHODS: The brachial plexus of 48 adult male rats was lesioned by either root avulsion close to the spinal cord or distal nerve transection. The rats were quickly revived and remained awake until death at 30, 60, or 120 min after surgery. In rats with avulsive injuries, traumatic sites on the dorsal and ventral horns of the spinal cord were microscopically detected. Immunocytochemical analysis of the c-fos product was performed for the two experimental groups and for sham-treated control animals at the same survival times. RESULTS: An increase in Fos-like immunoreactivity (FLI) in cells of the spinal cord, at levels C4-T1, was detected at 30 min after nerve transection or root avulsion. The number of FLI-positive cells continued to increase at 60 and 120 min after the nerve injury (P=0.001). FLI-positive cells were compared at the C7 level, in laminae 1 and 2, 3 and 4, and 5 to 10, after the two injuries and were found to be more abundant after the avulsive injury (P=0.0001); furthermore, the number of FLI-positive cells increased with time (P=0.001). In a comparison of all levels, both experimental groups demonstrated significantly greater numbers of FLI-positive cells than did controls, and the group with nerve root avulsion showed significantly (P=0.0001) more FLI-positive cells than did the group with distal nerve transection. CONCLUSION: These results suggest that nerve root avulsion from the spinal cord leads to increased and prolonged expression of c-fos and, potentially, greatly increased transcription of new messages for recovery, survival, or cell death.

Animals↗
PubMed1997

Neurotization of motor nerves innervating the lower extremity by utilizing the lower intercostal nerves.

An animal model in the rat was developed to study the reinnervation of ventral roots contributing to lower-extremity nerves by use of intercostal nerves. Intercostal nerves and distal cauda equina roots were anastomosed, using a collagen tube and microsurgical technique. Most experimental animals could lift their previously paralyzed legs and could walk with a severe limp by 9 months postoperatively. Recordings of nerve action potentials (NAPs) and muscle action potentials (MAPs) indicated that the intercostal and sciatic nerves had some functional connections. Histologic analysis 12 months after repair demonstrated axonal regeneration extending from the intercostal nerves to and down lumbar ventral roots. Most of the regenerated fibers were moderately well-myelinated. Connections between the neurons of the anterior horn cells in the lower thoracic spinal cord and the reinnervated sciatic nerve were confirmed by retrograde tracer, using fast blue.

Action Potentials↗
PubMed1997

Detection of substance P in human tears by laser desorption mass spectrometry and immunoassay.

PURPOSE: To determine whether substance P is present in human tears. METHODS: Tear samples (1-2 microliters) were collected from one eye of each of 12 subjects. Two of the eyes had dry eye syndrome, two wore contact lenses and had dry eye syndrome, and eight were normal. Five of the eight normal eyes were scheduled to undergo excimer laser refractive surgery, and tears were collected from these eyes before and after surgery. Tear samples were analyzed by laser desorption mass spectrometry. Pooled samples from one individual were subjected to enzyme-linked immunoabsorbent assay. RESULTS: Laser desorption mass spectra of the 18 tear samples displayed well defined peaks with mass to charge (m/z) ratios ranging from 1343.7 to 1355.9 and/or 1356.9 to 1364.7, corresponding to an average m/z of 1349.8 +/- 1.13 for protonated substance P and 1361.2 +/- 0.54 for oxidized substance P obtained from 14 mass spectra of standards formulated with substance P concentrations ranging from 10(-4) M to 10(-12) M. As confirmation, an enzyme-linked immunoabsorbent assay performed twice on pooled tears from one eye detected substance P in both replicates at a concentration of 125 pg/ml (9.26 x 10(-11) M). CONCLUSIONS: These findings demonstrate that substance P is a component of tears obtained from normal eyes of men and women ranging in age from 26 to 60 years, from eyes fitted with contact lenses, from eyes with dry eye syndrome, and from eyes 1 and 2 days after excimer laser refractive surgery. Whether the concentration of substance P in tears varies with sex, age, or eye condition, the source of substance P in tears, and its role in tears remains to be discovered.

Adult↗
PubMed1997

Growth factor and neurotrophic factor mRNA in human lacrimal gland.

PURPOSE: This study examined the expression of important growth factor and receptor messenger RNA (mRNA) in human lacrimal gland. METHOD: Lacrimal gland tissue was obtained from six women, aged 31-85 years, who were undergoing surgery. The specimens were frozen immediately in liquid nitrogen. Total cellular RNA was collected by cesium chloride centrifugation, and the integrity of the RNA was analyzed by gel electrophoresis and spectrophotometry. For the reverse-transcription polymerase chain reaction (RT-PCR) procedure, 1 microgram of total cellular RNA was used for the first strand synthesis and amplified in separate reactions for 34 cycles by using primers specific for transforming growth factor-beta 1, -beta 2, and -beta 3 (TGF beta 1, TGF beta 2, TGF beta 3), TGF beta 3 receptor (TGF beta 3R), basic fibroblast growth factor (bFGF), fibroblast growth factor receptor-1 (FGF-R1), nerve growth factor (beta-NGF), low-affinity NGF receptor (p75NGF-R), and platelet-derived growth factor-AA (PDGF-AA; two of the six cases) and -BB (PDGF-BB; three of the six cases). Product identity was confirmed by restriction endonuclease digestion, by the "hot blot" technique, by DNA sequencing, or by a combination of these. RESULTS: All the lacrimal gland specimens were positive for all growth factors, neurotrophic factors, and receptors except for two specimens that were negative for bFGF. The patients from whom the bFGF-negative specimens were obtained were 68 and 74 years old, and both were identified as having dry eyes-one severe and the other moderate, respectively. These specimens were also analyzed for PDGF-AA and PDGF-BB mRNA, and both were positive. CONCLUSIONS: This study demonstrates that RT-PCR is a rapid and sensitive method for analyzing rare mRNA transcripts in small amounts of tissue. The results suggest that these growth and neurotrophic factors may have autocrine and paracrine roles in modulating the lacrimal gland, and their absence may play a role in pathologic states such as fibrosis and dry eyes.

Adult↗
PubMed1996

Transient corneal stromal and endothelial changes following soft contact lens wear: a study with confocal microscopy.

PURPOSE: Previous studies have described transient corneal endothelial changes in non-contact lens wearers after a short period of soft contact lens wear by means of contact and noncontact specular microscopy and modified slit lamp biomicroscopy, which provide magnifications from 60 to 100x. In this investigation, we documented and characterized these contact lens-related corneal changes using the white light, real-time confocal microscope, which is capable of cellular resolution imaging of all layers within the cornea at magnifications of 100 to 500x. METHODS: We used a clinical confocal microscope to study corneal changes in three patients wearing a high water content soft contact lens for the first time. RESULTS: In one patient, endothelial changes consisting of irregularly shaped, round or oval, dark regions were observed within the endothelial mosaic. Scattered hyper-reflective keratocyte nuclei were seen in the posterior stroma. The keratocytic and endothelial changes were most evident 20 minutes after placement of the lens. By 30 minutes, the changes were fewer and less prominent, and the brightness of the highly reflective keratocyte nuclei had decreased. CONCLUSIONS: These studies show, for the first time, that the transient changes associated with contact lens wear occur not only in the endothelium, but also in the corneal stroma. It has been suggested that the changes result from an increase in CO2 and lactic acid, which causes a transient reduction in the corneal pH. We hypothesize that the resulting acidic environment may induce gene expression that causes changes in the involved nuclei, which in the keratocytes become hyper-reflective, and in the endothelium become enlarged, resulting in posterior displacement of the cell membrane and producing the dark "blebs" and irregular lines observed at this level of the posterior cornea.

Contact Lenses, Hydrophilic↗
PubMed1996

Diagnosis of bacterial contact lens related keratitis with the white-light confocal microscope.

PURPOSE: We used white-light confocal microscopy to identify the causative organisms in two patients with contact lens related keratitis. METHODS: The corneal infiltrates were examined by confocal microscopy and corneal specimens were obtained for culture. RESULTS: In both patients, confocal microscopy revealed 1.5- to 2-micron diameter hyper-reflective bodies below the level of the epithelium. The sizes of these structures were consistent with those of bacteria. The corneal cultures from one patient grew Staphylococcus werneri and the cultures from the other patient grew Streptococcus viridans. CONCLUSIONS: The confocal microscope permitted the in vivo observation of what we believe to be bacteria in patients diagnosed with contact lens related keratitis.

Adult↗
PubMed1995

Cell cycle kinetics in pterygium at three latitudes.

The cell cycle kinetics of 93 specimens of pterygial tissue, as well as 19 specimens of normal conjunctiva, from patients at three sites representing three different latitudes (Singapore, 1 degree; Hong Kong, 22 degrees; and Little Rock, Arkansas, 34 degrees) were evaluated by flow cytometry. The results showed no difference in cellular proliferation patterns between pterygial and conjunctival tissue at any of the sites, suggesting that pterygium is not a disorder of excess cellular proliferation. Transmission electron microscopy showed extracellular matrix to be a prominent component of pterygium. Cellular proliferation patterns of primary and recurrent pterygium were not significantly different from each other. Factors associated with increased incidence of pterygium included male sex, outdoor occupation, and advanced age.

Adult↗