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At least 919 records · Page 51Linked to original sources

Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye.

Approximately 1 out of every 10 eyes undergoing surgery for retinal detachment develops excessive intraocular fibrosis that can lead to traction retinal detachment and ultimate blindness. This disease process has been termed proliferative vitreoretinopathy (PVR). The ability to monitor and grade this fibrotic response accurately within the eye as well as the ability to aspirate vitreous cavity fluid bathing the fibrotic tissue makes this an ideal setting in which to investigate the development of fibrosis. Although laboratory studies have recently shown that transforming growth factor-beta (TGF-beta) can enhance fibrosis, little clinical evidence is yet available correlating the level of this or other growth factors with the degree of fibrosis in a clinical setting. We have found that vitreous aspirates from eyes with intraocular fibrosis associated with PVR have more than three times the amount of TGF-beta (1,200 +/- 300 pM [SEM]) found in eyes with uncomplicated retinal detachments without intraocular fibrosis (360 +/- 91 pM [SEM]). Using an in vitro assay, 84-100% of the TGF-beta activity could be blocked with specific antibodies against TGF-beta 2, whereas only 10-21% could be blocked by specific antibodies against TGF-beta 1. TGF-beta 1 was used in an animal model of traction retinal detachment. Since beta 1 and beta 2 have essentially identical biologic effects and only human beta 1 was available in quantities required, beta 1 was chosen for these in vivo studies. The injection of TGF-beta1 plus fibronectin (FN) but not TGF-beta1 alone into the vitreous cavity of rabbits resulted in the increased formation of intraocular fibrosis and traction retinal detachments as compared to control eyes. In previous studies, intravitreal FN levels were also found to be elevated in eyes with intraocular fibrosis.

Adolescent↗

Study of central regulation of intraocular pressure using ventriculocisternal perfusion.

The ability of hypoosmotic solution, prostaglandin E1 (PGE1) and clonidine to influence intraocular pressure (IOP) by a central mechanism was studied using the technique of ventriculocisternal perfusion in conscious rabbits. IOP remained unchanged during the perfusion of 150 mOsm artificial cerebrospinal fluid. IOP rapidly increased by 15 mmHg during the perfusion of PGE1 at the dose of 1 or 3 micrograms/min. However, when PGE1 was perfused intravenously at the dose of 1 microgram/min, a similar IOP response was observed. Furthermore, during the ventriculocisternal perfusion of PGE1 a significant systemic absorption occurred. These observations indicate that the ocular hypertension during the ventriculocisternal perfusion of PGE1 is primarily due to the peripheral action of systematically absorbed PGE1. IOP gradually decreased by 3 mmHg during the ventriculocisternal perfusion of clonidine at the dose of 0.1 or 0.33 micrograms/min. Intravenous perfusion of clonidine at the same doses did not change the IOP. These results indicate that clonidine can lower IOP by a centrally mediated mechanism. Ventriculocisternal perfusion of clonidine (0.1 micrograms/min) in rabbits with unilateral superior cervical ganglionectomy lowered IOP in both eyes, indicating that ocular adrenergic innervation does not participate in this centrally mediated IOP response. However, the cardiovascular parameters of anesthetized rabbits were altered by the ventriculocisternal perfusion of clonidine (0.1 micrograms/min), suggesting that a change in systemic hemodynamics is involved in the central IOP effect of clonidine.

Alprostadil↗

Ridley intraocular lens revisited: chemical analysis of residuals in the original lens material.

Two original Ridley intraocular lenses, made of poly(methyl methacrylate) (PMMA) at least 35 years ago, were extracted in two different media, diethyl ether and water. The extracts were suitably processed and analyzed by high resolution capillary gas chromatography. Residual monomer (MMA) was detected in both extracts. The amount of MMA in the aqueous extract was significantly lower than that in the ether extract. It is postulated that the residual monomer in lenses originated from an incomplete polymerization at the time of the polymer production. However, the MMA content found in one lens (0.147%) is comparable to that currently detected in modern IOLs, and probably does not cause toxic reaction in the eye because it is leached out by aqueous fluid action to a very low extent.

Chromatography, Gas↗

Iris retraction associated with rhegmatogenous retinal detachment syndrome and hypotony. A new explanation.

Eyes with rhegmatogenous retinal detachment can occasionally be seen with hypotony and a peculiar retraction of the peripheral iris. Herein I report the following new observations in this syndrome: (1) seclusion of the pupil, (2) resolution of the retraction configuration after disruption of the seclusion, (3) the initial manifestation as angle closure secondary to iris bombé interchangeable with the iris retraction configuration with the addition (to bombé) and the withdrawal (from retraction) of pharmacologic aqueous suppressants, and (4) the rapid cataract formation. The theory that vitreous traction or retraction is the cause of the retrodisplacement of the iris was disproved. A hydrodynamic theory is presented. A lowering of pressure behind the iris, at least partially, due to posterior removal of fluid, presumably from the subretinal space, was shown to be the cause of the iris retraction. The iris retrodisplacement occurred when posterior aqueous removal exceeded aqueous formation. This removal of fluid may be an important factor in the understanding of proliferative vitreoretinopathy as the fluid flow involved may draw cells posteriorly.

Acetazolamide↗

Diagnostic yield of vitrectomy in eyes with suspected posterior segment infection or malignancy.

PURPOSE: To determine the yield of diagnostic pars plana vitrectomy in eyes with suspected posterior segment inflammation or malignancy when clinical examination and systemic laboratory testing did not yield a specific diagnosis. DESIGN: Non-comparative interventional case series PARTICIPANTS: Eighty-seven consecutive patients (90 eyes) who underwent diagnostic pars plana vitrectomy from 1989 through 1999. INTERVENTIONS: Vitreous samples were analyzed in a directed manner based on the preoperative clinical examination and systemic laboratory testing. MAIN OUTCOME MEASURES: Diagnosis from each test performed on the vitreous samples. RESULTS: Diagnostic vitrectomy was performed alone in 6 eyes (7%) and as part of a therapeutic procedure in the remaining 84 eyes. The diagnostic tests performed most frequently included cytopathology (83%), microbiologic culture and sensitivity (43%), polymerase chain reaction (PCR) (36%), and intraocular antibody levels for T. canis (14%). Of these, intraocular antibody testing and PCR had the highest positive yield, 46% and 39%, respectively. Overall, directed vitreous analysis identified a specific cause in 35 eyes (39%). Of the 65 cases in which an underlying infection was suspected preoperatively, the procedure yielded a specific diagnosis in 27 (42%). When intraocular malignancy was considered preoperatively (71 eyes), a diagnosis of intraocular lymphoma was obtained in seven (10%). This difference between these diagnostic yields was significant (P = 0.02, Fisher's exact test). CONCLUSIONS: Diagnostic vitrectomy with directed vitreous fluid analysis yields a specific cause and guides subsequent therapy in a high percentage of cases. This procedure is a valuable adjunct in cases that cannot be diagnosed by less invasive methods.

Adolescent↗

Ocular pharmacokinetic/ pharmacodynamic modeling for bunazosin after instillation into rabbits.

PURPOSE: To develop a pharmacokinetic/pharmacodynamic (PK/PD) model for an alpha1-blocker (bunazosin) after instillation. The PK/PD model can predict both the drug concentrations in various ocular tissues and the hypotensive effect. METHODS: Bunazosin concentrations were determined with High Performance Liquid Chromatography (HPLC) in tear fluid, the aqueous humor, cornea, and iris-ciliary body after instillation or ocular injection into the anterior chamber in rabbits. After instillation of bunazosin in rabbits, intraocular pressure (IOP) was also determined with a pneumatic tonometer. The PK/PD parameters were estimated by fitting the concentration-time profiles and the hypotensive effect-time profiles to the developed PK/PD models using the MULTI (RUNGE) program. RESULTS: On the basis of the concentration-time profiles of bunazosin, a PK model, including seven compartments, was developed for examining the behavior of bunazosin after instillation. Then, two PK/ PD models for hypotensive effect of bunazosin were developed using an indirect response (model A) and the relationship between IOP and aqueous humor flow (model B). These models well described the concentration-time profiles and hypotensive effect-time profiles of bunazosin after instillation. CONCLUSIONS: This study is the first trial to develop a PK/PD model for an antiglaucoma agent using an indirect response and the relationship between IOP and aqueous humor flow.

Adrenergic alpha-Antagonists↗

Myocilin is expressed in the glomerulus of the kidney and induced in mesangioproliferative glomerulonephritis.

BACKGROUND: Myocilin is a 55 to 57 kD secreted glycoprotein and member of the olfactomedin protein family. It is expressed in high amounts in the outflow tissues of the aqueous humor in the eye where it is supposed to contribute to outflow resistance. Myocilin is mutated in some forms of primary open angle glaucoma and affected patients show very high intraocular pressures because of an increase in resistance to aqueous humor outflow. To obtain information, if myocilin may play a comparable role in other tissues with transendothelial fluid flow, we investigated its expression in the rat kidney. METHODS: The expression of myocilin in the normal rat kidney and its changes during mesangioproliferative glomerulonephritis were investigated by immunohistochemistry, one- and two-dimensional gel electrophoresis with Western blotting, and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Myocilin and its mRNA were detected in isolated glomeruli. Immunohistochemistry showed specific labeling of glomerular cells, while tubular and interstitial regions were essentially negative. Double staining with the podocyte-specific markers synaptopodin and ezrin indicated that myocilin-positive cells were predominately podocytes. During mesangioproliferative glomerulonephritis, an induction of myocilin immunoreactivity was observed. Labeling for myocilin was now observed in activated mesangial cells and areas of glomerular sclerosis. In parallel cell culture experiments, mRNA for myocilin was detected in cultured murine podocytes and rat mesangial cells. CONCLUSION: Myocilin is expressed in podocytes of the kidney and induced in mesangial cells during experimental mesangioproliferative glomerulonephritis. The specific function of myocilin in the kidney is not clear, but in a parallel to functions of other olfactomedin proteins, it might have a role in cell-cell adhesion and/or signaling processes.

Animals↗

B-scan echographic measurement of endobulbar foreign bodies.

Echography plays an important role in symptomatology investigations of ocular traumatology. Trauma causes the opacification of eye fluids, and so echography is particularly suitable for studying the endobulbar situation. We wished to enrich ocular investigations with another methodology: ultrasonic evaluation of the dimensions of intraocular foreign bodies, and report here the results obtained with experimental studies introducing foreign bodies into enucleated bovine eyes.

Animals↗

Carbonic Anhydrase Inhibitors. Synthesis of Topically Effective Intraocular Pressure Lowering Agents Derived from 5-(omega-Amino- alkylcarboxamido)-1,3,4-Thia- diazole-2-Sulfonamide.

Reaction of the acyl chlorides of phthalimido-glycine or phthalimido-beta-alanine with 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded after hydrazinolysis and deprotection of the phthalimido group the corresponding 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamides. Reaction of 5-(beta-aminoethylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide with sulfonyl halides or acyl halides afforded a series of compounds possessing beta-alkyl/arylsulfonyl/carbonylamidoethylcarboxamido moieties in the 5 position of the thiadiazole-2-sulfonamide ring. The new derivatives were efficient inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form), but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play an important role in aqueous humor secretion within the ciliary processes of the eye. Some of the synthesized inhibitors possessed good water solubility (as hydrochlorides or sodium salts) and were applied as 2% solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them for prolonged periods of 1-2 h, and the active drug was detected in eye tissues and fluids indicating that the antiglaucoma effect is due to CA inhibition within the eye.

Journal Article↗

[Results of combined use of taufon and timolol in the treatment of patients with open-angle glaucoma].

The effect of taufon and timolol maleate combination on intraocular pressure and ocular hemodynamics was studied in 44 patients (63 eyes) with primary open-angle glaucoma. Combined administration of these agents elevated almost twofold the fluid discharge efficacy coefficient and normalized Becker's coefficient in 68.6 percent of patients. The patients were followed up for 8 weeks. Taufon addition to timolol modified the action of this latter drug, normalizing the ocular hemodynamics.

Adult↗

[Clinical aspects of leukemic infiltration of the choroid and the optic nerve].

A case of presumed leukemic infiltration of the choroid and two cases of leukemic involvement of the optic nerve are presented. These complications are rarely observed clinically. Leukemic infiltration of the choroid may cause a serous detachment of the retina, which is often bilateral. The fluoroangiographic aspect is similar to what is observed in acute choriocapillaris occlusion. Leukemic involvement of the optic nerve first appears as papilledema. In more advanced cases the optic disc and the peripapillary retina are covered by a white-yellowish infiltrate which protrudes into the vitreous. The diagnosis is confirmed by CT scan of the orbit and the cerebro-spinal fluid often contains leukemic cells. As optic nerve infiltration is often associated with CNS involvement the prognosis is usually poor. Intrathecal chemotherapy has little effect on the intraocular manifestations, which however respond to orbital radiotherapy.

Adult↗

[Expulsive retinal hemorrhage. Secondary treatment by vitreoretinal surgery].

Expulsive hemorrhage is a catastrophic complication of intraocular surgery that can result in total loss of vision. Patients with massive hemorrhagic choroidal detachment were treated by vitrectomy and silicone oil or gas tamponade. A reattachment of the retina was achieved with stabilization of visual function. Properly timed drainage of the choroidal fluid components with pars plana vitrectomy and silicone or gas injection is a useful approach in these disorders and may salvage useful vision in complicated cases.

Adult↗

Ultrasound activates the TM ELAM-1/IL-1/NF-kappaB response: a potential mechanism for intraocular pressure reduction after phacoemulsification.

PURPOSE: Elevated intraocular pressure (IOP), the major causal risk factor for glaucoma, often decreases after cataract removal by phacoemulsification ultrasound. In this study, the hypothesis that ultrasound energy propagated through a fluid medium induces a stress response with the potential to lower IOP was investigated. METHODS: Normal and glaucomatous trabecular meshwork (TM) cell culture lines were initiated from tissue isolated from human cadaveric eyes or trabeculectomy specimens. Cultured cells were treated for 60 seconds with a phacoemulsification ultrasound probe set to a power of 70%. Activation of the TM cell-specific stress response was assayed by enzyme-linked immunosorbent assay (ELISA) and immunolocalization. RESULTS: Normal TM cell cultures did not release detectable levels of the stress response protein, IL-1alpha, into their culture medium. In contrast, IL-1alpha was easily detected after treatment with ultrasound energy. Consistent with earlier findings, glaucomatous TM cells produced IL-1alpha constitutively, and the level of expression was increased after treatment with phacoemulsification ultrasound. As was previously demonstrated, the stress-regulated transcription factor NF-kappaB was present in the cytoplasm of normal cells, but in the nucleus of glaucomatous cells. After treatment with ultrasound energy, NF-kappaB translocated to the nucleus in the normal cells. Endothelial leukocyte-adhesion molecule (ELAM)-1 was not detected in normal TM cells, but was constitutively present on glaucomatous TM cells, consistent with findings in previous work. ELAM-1 expression was induced in normal cells by ultrasound treatment. CONCLUSIONS: A potentially IOP-lowering stress response is induced in TM cells by ultrasound. The findings suggest that this response may be induced clinically during cataract removal by phacoemulsification, and may be one mechanism responsible for the reduction in IOP that often follows this procedure.

Cells, Cultured↗

Low mature TGF-beta 2 levels in aqueous humor during uveitis.

PURPOSE: To investigate whether transforming growth factor-beta 2 (TGF-beta 2), a strong immunosuppressive factor normally present in aqueous humor, is involved in the inflammatory process of clinical uveitis. METHODS: Mature TGF-beta 2 levels were determined in aqueous humor samples of 9 patients with Fuchs' heterochromic cyclitis, aqueous humor samples of 21 patients with other uveitis entities, and vitreous fluid samples of 19 patients with uveitis by using a commercially available sandwich ELISA: Total TGF-beta 2 levels in ocular fluids were measured after heat activation. Aqueous humor samples from patients with cataract and glaucoma and vitreous fluid samples from eye bank eyes were tested as controls. Albumin levels, determined by radial immunodiffusion, were used as a measure of the disruption of the blood aqueous barrier. RESULTS: Significantly lower mature TGF-beta 2 levels were detected in aqueous humor samples of patients with uveitis, compared to the two control groups without intraocular inflammation. Samples of patients with uveitis without detectable mature TGF-beta 2 did contain latent TGF-beta 2 levels (504 to 6024 pg/ml). In aqueous humor, there was a significant negative correlation between mature TGF-beta 2 and albumin levels. No mature TGF-beta could be detected in vitreous fluid. Total TGF-beta 2 levels in vitreous fluid were significantly lower in samples from patients with uveitis than in samples from eye bank eyes. CONCLUSION: These results indicate that the mature TGF-beta 2 levels in aqueous humor and the total TGF-beta 2 levels in vitreous fluid are reduced during ocular inflammation. In aqueous humor, this might be caused by binding of mature TGF-beta to serum proteins, for instance, alpha 2-macroglobulin, or by a disturbance in the activation process of latent TGF-beta 2.

Aqueous Humor↗

Review of optical coherence tomography for intraocular tumors.

PURPOSE OF REVIEW: Optical coherence tomography has assumed an important role in the management of numerous ocular conditions. With regard to ocular oncology, optical coherence tomography can illustrate retinal changes overlying choroidal tumors. Some of these features include photoreceptor loss, intraretinal edema, and retinal thinning overlying choroidal nevus; fresh subretinal fluid with preservation of photoreceptors overlying choroidal melanoma; and intraretinal edema, retinoschisis, and retinal thinning overlying irradiated choroidal melanoma. RECENT FINDINGS: The optical coherence tomography features of tumors of the retinal pigment epithelium include typical findings of peaked vitreoretinal traction and retinal disorganization with combined hamartoma of the retina and retinal pigment epithelium, full-thickness retinal shadowing with congenital simple hamartoma, and photoreceptor loss and retinal thinning overlying congenital hypertrophy of the retinal pigment epithelium. SUMMARY: Optical coherence tomography of retinal tumors, such as retinoblastoma and astrocytic hamartoma, reveals full-thickness replacement of the retinal anatomic layers with the tumor and shadowing corresponding to the intralesional calcification. For all intraocular tumors, optical coherence tomography provides valuable information regarding the status of the retina and the retinal pigment epithelium and can be useful in ascertaining reasons for visual loss.

Choroid Neoplasms↗

[Clinical and immunological factors in predicting an early exudative reaction after extraction of senile cataracts with implantation of elastic IOL].

Clinical and immunological studies in 170 patients with senile cataracts carried out before and during the first 7 days after cataract extraction with implantation of intraocular lenses helped define the risk factors for development of an early exudative reaction: patients' age under 60 years, clinical signs of secondary immune deficiency presenting as infection syndrome, increased levels of nonspecific immunity factors with deterioration of the phagocytic component, T-lymphopenia, CD4/CD8 imbalance, and increased levels of interleukin-1 beta and tumor necrosis factor in the serum and lacrimal fluid.

Aged↗

Trabeculectomy with releasable sutures.

OBJECTIVE: To determine whether the use of releasable scleral-flap sutures affects the success rate and the incidence of complications following trabeculectomy. DESIGN: A retrospective chart review of a consecutive series of trabeculectomies. SETTING: A university-based referral practice. PATIENTS: Two hundred fifty-eight consecutive patients (274 eyes) undergoing trabeculectomy because of uncontrolled glaucoma. INTERVENTION: During the first year, 124 patients (128 eyes) underwent trabeculectomies with permanent scleral-flap sutures. During the second year, 134 patients (146 eyes) underwent trabeculectomies with releasable scleral-flap sutures. MAIN OUTCOME MEASURES: Incidence of flat and shallow anterior chamber, incidence of operations to drain choroidal detachment and to re-form anterior chamber, and long-term control of intraocular pressure. RESULTS: In the group with permanent sutures, 42 eyes (32.8%) had clinically detectable shallowing of the anterior chamber in the early postoperative period. In contrast, a shallow anterior chamber was noted in 21 eyes (14.4%) in the group with releasable sutures (P = .0003). Flat anterior chamber, defined as iridocorneal apposition to the pupil margin, occurred in 11 eyes with permanent sutures (8.6%) but in only two eyes (1.4%) with releasable sutures (P = .0078). Surgical intervention to drain suprachoroidal fluid and re-form the anterior chamber was required in eight eyes with permanent sutures (6.2%) but in only one eye with releasable sutures (0.7%) (P = .014). At 1-year follow-up, the two groups were similar in terms of intraocular pressure and the need for ocular hypotensive medications. CONCLUSIONS: Releasable scleral-flap sutures reduce the incidence of shallow and flat anterior chamber after trabeculectomy without compromising long-term control of intraocular pressure.

Aged↗

C-kinase manipulations disrupt activity-driven retinotopic sharpening in regenerating goldfish retinotectal projection.

Regenerating optic axons initially branch over a wide area in tectum to form a crude retinotopic map. The map is sharpened, and retinotopically appropriate synapses are stabilized via NMDA receptors that detect, via summation of EPSPs, the coincident activity of neighboring ganglion cells that make synapses onto common tectal cells. Sharpening shares a number of properties with long-term potentiation (LTP) in hippocampus. This study tested whether protein kinase C (PKC) activation is necessary for sharpening as it is for LTP. Intraocular (IO) or intracranial (IC) injections of kinase inhibitors or activators were made every other day from 19 to 37 days postcrush (sensitive period), and the projections formed were later recorded. Retinotopic sharpening was prevented by IC injection of the following agents: (1) general kinase inhibitors sphingosine and H7 (100-200 microM in fluid above brain), (2) active but not inactive phorbols (TPA, 1 microM), and (3) calphostin C (1 microM), a specific and irreversible PKC inhibitor. The mature projection on the opposite tectum, however, when examined was not unsharpened. Lack of sharpening was reflected in multiunit fields at each tectal point that averaged 27 degrees-30 degrees versus 11 degrees in Ringers and inactive phorbol control regenerates. Intraocular injections of either TPA (1 microM), or calphostin C (1 microM) also prevented sharpening (26 degrees and 32 degrees multiunit fields), suggesting action on PKC axonally transported to the presynaptic terminals. Calphostin C had no noticeable effect on the firing patterns of retinal ganglion cells. The endogenous activator of PKC, arachidonic acid (AA), disrupted sharpening at 20 microM or higher (IC injection, 32 degrees multiunit fields), while a control fatty acid, elaidic acid, had no effect. Although AA at 5 microM showed no effect, and diacylglycerol at 5 microM exhibited only small effects, together they produced a large synergistic effect (32 degrees multiunit fields). Such synergy mirrors the synergy in the activation of several isoforms of PKC. Actual concentrations in the extradural fluid around the brain were assayed via injections of 3H-AA. Levels fell about sixfold after a day and by an additional fivefold the second day before the next injection. The results confirm that activity-driven retinotopic sharpening is very sensitive to manipulations of kinases, especially PKC.

Animals↗