Glaucomatous optic neuropathy.
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Biomedical subjects
Publications and source records attributed to E M Van Buskirk.
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A trabeculectomy technique with conventional instruments, but without conjunctival incision or intracameral manipulation, was completed in 12 eye-bank eyes, two cat eyes, and in five patients with glaucoma. A partial-thickness limbal corneal flap provided access to an intrastromal limbal pocket through which the subconjunctival space was entered with an irrigating cystotome. The anterior chamber was entered at the surgical corneoscleral limbus beneath the corneal flap and the peripheral iridectomy was completed without difficulty. Full-thickness or guarded limbal fistulas could be created. Guarded limbal fistulas were completed in five of five patients with glaucoma. The technique produced low-lying, diffuse filtration blebs that persisted throughout the three-month postoperative period and reduced mean intraocular pressure from 33 to 12 mm Hg. Corneal trabeculectomy holds promise as a method for a filtration operation that does not require conjunctival incision, intracameral manipulation, or costly technology.
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Vascular luminal castings of rabbit eyes were microdissected and studied with scanning electron microscopy to elucidate the three-dimensional angioarchitecture of the optic nerve head. Using sequential microdissection, an incomplete arterial circle was identified as terminal branches of two to three short posterior ciliary arteries around the optic nerve head. Several recurrent branches from the arterial circle form a pial arterial network. This pial system supplies the optic nerve head microvasculature and receives numerous venules from them. The only large vessel to enter the optic nerve is a central retinal artery that has few branches within the optic nerve and provides several branches at the surface of the optic disc. Moderately numerous vessels connect the retinal and ciliary vascular layers within the optic nerve head. Few arterioles to the optic nerve head arise from the choroid; however, there are a small number of capillary and numerous venous connections between them. These results indicate that the principal blood supply of the rabbit optic nerve head is derived from the short posterior ciliary arteries by the arterial circle. The retinal arteries contribute to the surface vasculature of the optic nerve head. The pial system also plays a significant role in both supply and drainage of the rabbit optic nerve head.
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The effect of exercise conditioning on elevated intraocular pressure has not been previously described among sedentary individuals. We prospectively observed intraocular pressure for nine sedentary subjects suspected of having glaucoma before and after 3 months of aerobic exercise training. Mean (+/- SEM) aerobic capacity, as assessed by maximal oxygen uptake, increased 6.3 +/- 1.6 mL.kg-1.min-1 (30%) (P less than .02). Mean intraocular pressure decreased 4.6 +/- 0.4 mmHg (20%) (P less than .001) at the end of the conditioning period. With cessation of exercise and subsequent detraining, intraocular pressure returned to elevated preconditioning levels by 3 weeks. Regular aerobic exercise is associated with a reduction in elevated intraocular pressure and may represent an effective nonpharmacologic intervention for patients suspected of having glaucoma.
Extracellular matrix (ECM) turnover and remodeling are initiated, at least in part, by the regulated secretion of members of a family of matrix metalloproteinases. Human and bovine trabecular mesh-work in culture secrete interstitial collagenase, both the 72- and the 92-kD forms of type IV collagenase (gelatinases) and stromelysin, and the tissue inhibitor of metalloproteinases (TIMP). These proteinases and TIMP were identified by immunoblotting western transfers from sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) using several specific antiprotein and antipeptide polyclonal antibodies. Gelatinase and stromelysin enzymatic activities were also analyzed by substrate SDS-PAGE, in which proteinase substrates were polymerized into the gels before electrophoresis to allow subsequent activity assays. These matrix metalloproteinases and TIMP are secreted at low basal levels into trabecular culture medium; their secretion levels are increased several-fold by treatment of the cultures with the phorbol mitogen. 12-O-tetradecanoylphorbol-13-acetate (TPA). Characteristics of the trabecular matrix metalloproteinases and TIMP are similar to those secreted by numerous other tissues, including the retinal pigment epithelium. These proteinases may serve an important role in the maintenance and regulation of the trabecular extracellular matrix and, subsequently, of the aqueous humor outflow pathway in normal and glaucomatous eyes.
Rabbits underwent the single-dose or long-term therapeutic administration of the adrenergic drugs phenylephrine hydrochloride, timolol maleate, and betaxolol hydrochloride. After a single dose, all three drugs caused substantial, localized constriction in the arterioles that supply the ciliary processes but did not affect the downstream bore of the same vessels. After seven weeks of a daily dose, tolerance reduced the response to betaxolol to insignificant levels and that to phenylephrine substantially, whereas timolol maleate continued to produce identical levels of vasoconstriction to those seen with single-dose administration. In addition to the consequent lowering of perfusion of the ciliary processes and presumptive impact on aqueous humor production, vasoconstriction also reinforces concerns about impaired vascular perfusion of eyes undergoing long-term ocular therapy.
To study further the transient increase in trabecular cell division within the first two days after laser trabeculoplasty in human corneoscleral explant organ cultures, we used a pulse-chase protocol in which immediately after laser treatment 3H-thymidine was added to the culture medium for 48 hours (the pulse period). Fresh medium without radiolabel was then added for variable times (the chase period) before termination of the experiment. Autoradiography was used to follow changes in the regional distribution of the cells that divided during the pulse period and had 3H-thymidine-labeled DNA. Laser-treated explants, evaluated after a pulse with no chase, showed a fourfold increase in cell division (P less than .001) over nontreated controls. Nearly 60% of this cell division was localized to the anterior, nonfiltering region of the trabecular meshwork where it inserts into the cornea beneath Schwalbe's line. Trabecular cell division in other regions of the meshwork was not increased over controls at this time. After seven or 14 days of chase without radiolabel, the regional distribution of radiolabeled cells changed in laser-treated explants but not in controls. By 14 days, only 26% of the labeled cells remained in this anterior insert region, while 60% were found in the region of the burn sites. Macroautoradiography of whole explants corroborated these observations. Our data support the hypothesis that laser trabeculoplasty causes early cell division by a population of cells in the anterior meshwork; these new cells then migrate and repopulate the burn sites over the next few weeks.
The limbus forms the border between the transparent cornea and opaque sclera, contains the pathways of aqueous humour outflow, and is the site of surgical incisions for cataract and glaucoma. Externally the epithelial cell border between conjunctiva and cornea possesses multipotential cells important for differentiation of the respective cell types. By the same token, the internal limbal border zone between corneal endothelium and anterior trabeculum appears to contain specialised cells some of which are activated to migrate and repopulate the trabecular meshwork after trabecular injury. The oblique interface between corneal and scleral stroma determines the appearance of the surgical limbus whose landmarks vary around the circumference of the globe but predictably correlate with structures of the anterior chamber angle. The vasculature of the limbus derives in primates primarily from the anterior ciliary arteries. Their superficial branches form arcades to supply the limbal conjunctiva and peripheral cornea. Perforating branches contribute to the vascular supplies of the deep limbal structures and the anterior uvea.
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A select population of patients received repeat laser trabeculoplasties of 40 to 100 burns over 180 to 360 degrees. These eyes had shown an excellent prolonged response to initial laser trabeculoplasty. Eight of 11 eyes with greater than one year follow-up showed a sustained hypotensive response to repeat laser trabeculoplasty. No significant posttreatment intraocular pressure increases were observed. Repeat argon laser trabeculoplasty was effective for these patients who had shown a prolonged response to their initial treatment.
The usefulness of argon laser trabeculoplasty (ALT) in the treatment of some patients with glaucoma has been established; yet, the mechanism of ALT is not understood. The hypothesis that the mechanism involves trabecular cell division was examined. Autoradiographic assessment of tritiated thymidine incorporation into trabecular cell DNA in a human corneoscleral explant organ culture system demonstrated a basal level of DNA replication that increased by 180% in the two days immediately after ALT. When labeling was initiated five days after ALT, DNA replication declined to 70% of the control level. The autoradiographic findings were confirmed using biochemical evaluation of tritiated thymidine incorporation into acid-precipitable macromolecules (DNA) in excised trabecular meshwork. One biologic response of the trabecular meshwork after laser trabeculoplasty is a change in the level of ongoing trabecular cell division.
We have refined the technique of vascular corrosion casting with methacrylate to permit the reproduction of physiological states of vascular tone and to produce sturdy castings of ocular microvasculature. The method entails careful maintenance of homeostasis up to the moment of plastic perfusion, avoidance of vascular rinsing or fixation with the attendant anoxia, reduction of the viscosity of the casting resin without impairing the properties of the resultant polymer, addition of a cross-linking agent to increase the strength of the plastic, and injection at physiological temperature and pressure. This casting regimen reproduces the normal anatomical conditions of blood vessels and can be used to demonstrate altered conditions of vascular tone. In all instances, the second, untouched eye serves as a control for unilateral manipulations. Special problems of replicating the ocular vasculature are related to the intraocular pressure, which opposes the vascular perfusion pressure and constitutes an impediment to perfusion.
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Human corneoscleral explants were maintained for several weeks in defined, serum-free media. Trabecular cell vitality, as judged by vital stain exclusion, is high for at least one month. Trabecular ultrastructure, as compared to that of fresh eyes, first shows minor cellular and extracellular matrix degradation after 3 weeks in culture. The biosynthetic profiles of trabecular glycosaminoglycans (GAGs) change significantly by 3 weeks in culture. Eyes that are stored at 5 degrees C for up to 48 hr postmortem exhibit changes in trabecular ultrastructure and in GAG profiles; both characteristics return to normal by 7 days in culture. The incorporation pattern of 35S-sulfate and 3H-glucosamine into the GAGs of the trabecular meshwork (TM) is distinct from corneal or scleral incorporation. The relative incorporation of 3H-glucosamine into trabecular GAGs, as determined by sequential enzymatic degradation, is: 22.3% hyaluronic acid (HA), 27.9% chondroitin sulfate (CS), 21.3% dermatan sulfate (DS), 5.9% keratan sulfate (KS), 17.7% heparan sulfate (HS) and 4.9% unidentified material. The relative incorporation of 35S-sulfate into trabecular GAGs is: 0% HA, 32.9% CS, 34.8% DS, 7.7% KS, 13.8% HS and 11.1% into unidentified material. This profile is in good agreement with the profile that was previously obtained for human and nonhuman primate meshworks prior to culture. We conclude that corneoscleral explant organ culture is a useful tool for extracellular matrix studies within a time window from 7 to at least 14 days in culture.
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