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[Noncompaction of the left ventricular myocardium. Case report and review of the literature].

Left ventricular non-compaction is an unclassified cardiomyopathy characterized by an excessively prominent trabecular meshwork due to an arrest in myocardial morphogenesis. We report on a 51-year-old female patient with abnormal myocardial trabeculations associated with a congenital mitral valve stenosis post commissurotomy at the age of 14. In the present case report, clinical manifestation of the disorder included impaired left ventricular systolic function and atrial fibrillation. Noncompaction was diagnosed by echocardiography and levocardiography. In addition, a review of the literature on this rare disorder is presented.

Adolescent↗

Plasminogen activator inhibitor-1 mRNA expression in cultured pigmented ciliary epithelial cells of the porcine eye.

BACKGROUND: Plasminogen activator inhibitor-1 (PAI-1) is a main regulator of the fibrinolytic system. PAI-1 inhibits tissue plasminogen activator and urokinase-type plasminogen activator, resulting in reduced plasminogen activity and attenuated fibrinolysis and proteolysis. The present study was performed to determine the gene expression encoding for PAI-1 in cultured pigmented ciliary epithelial cells of the porcine eye and to detect PAI-1 activity in cell culture supernatants. METHODS: Total mRNA of respective confluent primary cultures of porcine ciliary epithelial cells, porcine liver cells and porcine kidney cells was isolated. Reverse transcribed PAI-1 mRNA was measured by real-time polymerase chain reaction (TaqMan PCR) with PAI-1 primers and probes deduced from the human PAI-1 gene. PAI-1 activity in supernatants of the cell cultures was determined by a specific chromogenic test (Coatest PAI). RESULTS: PAI-1 mRNA was localized in all samples of primary cultures of porcine pigmented ciliary epithelial cells. As a negative control we analyzed total mRNA of porcine kidney cells. PAI-1 mRNA was not detectable in these cells. On the other hand, we established PAI-1 mRNA in porcine liver cells as a positive control. High levels of PAI-1 activity were found in all samples of cell culture supernatants. CONCLUSIONS: Our results indicate that PAI-1 is produced and secreted by the porcine ciliary epithelium. We suggest that PAI-1 together with components of the fibrin/fibrinolytic system may be involved in aqueous humor outflow. Overproduction of PAI-1 may induce less fibrinolysis and extracellular proteolysis in aqueous humor and trabecular meshwork, which could result in an elevated intraocular pressure by increasing the outflow obstruction. Therefore stimulation of PAI-1 production may perhaps contribute to the pathogenesis of primary open-angle glaucoma.

Animals↗

The influence of Latanoprost 0.005% on aqueous humor flow and outflow facility in glaucoma patients: a double-masked placebo-controlled clinical study.

BACKGROUND: Fluorophotometry and pneumotonography were performed to investigate the effect of Latanoprost 0.005% and Placebo on aqueous humor flow and total outflow facility in human glaucomatous eyes. METHODS: In a randomized double-blind clinical study patients with POAG and OHT receive either Latanoprost 0.005% or placebo once in the evening. Fluorophotometry (Fluorotron Master II, Ocumetrics) and, Pneumotonography, Mentor) was performed in 20 eyes of 10 patients (verum) and 22 eyes of 11 patients (placebo). During a 2 week wash-out period all patients received a systemic antiglaucomatous therapy (Acetazolamide) up to 3 days before baseline measurement. Patients with IOP higher than 28 mmHg at baseline were excluded. Fluorophotometry, tonography and IOP were measured at baseline after 1 and 2 weeks of treatment. Data was analysed by the Student's paired t test. RESULTS: All patients completed the protocol. The IOP significantly decreased (25%) after 1 and 2 weeks of treatment with Latanoprost(p<0.01). Fluorophotometry measurements showed no difference in flow over time in both groups. Although tonographic mean C values in both groups did not show any difference over time, the estimated total outflow facility C (Goldmann) increased significantly (p<0.05) in the verum-treated eyes after 2 weeks. A significant difference of outflow co-efficient correlated to normal pressure (P0/C) was found after 2 weeks of treatment with Latanoprost (p<0.05). CONCLUSIONS: In accordance with the literature we found a mean 25% decrease in IOP after 2 weeks of treatment with Latanoprost 0.005%. The analysis of the flow values in both groups showed no increase or decrease in aqueous humor dynamics as proved in many previous studies. The known effect of Latanoprost increase uveoscleral outflow by remodeling extracellular matrix and widening intermuscular spaces in the ciliary body may not detected by pneumotonography after 2 weeks of treatment. The significant increase in estimated total outflow facility (Goldmann formula) in latanoprost-treated eyes and the decrease of IOP took place at constant flow rates. The increase in conventional outflow facility may indicate trabecular meshwork changes, but it cannot explain the significant decrease in IOP. Furthermore, an additional effect, e.g. uveoscleral outflow, may play the major role as considered in many previous studies.

Adult↗

The expression of myocilin during murine eye development.

PURPOSE: To study the expression and localization of myocilin in the developing mouse eye. Myocilin is a 55- to 57-kDa secreted glycoprotein that is mutated in some forms of primary open-angle glaucoma. METHODS: The eyes of NMRI mice were studied from embryonic day (E) 14.5 to postnatal day (P) 21, and at 2-3 months of age. Immunohistochemistry was performed with antibodies against myocilin. The specificity of the antibodies was checked by two-dimensional gel electrophoresis. RNA was isolated from eyes at various ages, and the presence of myocilin mRNA was analyzed by northern blot hybridization. RESULTS: No immunostaining for myocilin was seen before E16.5. At around E17.5, a distinct positive immunoreactivity of optic nerve axons in the developing nerve fiber layer of the retina was observed. At P5-6, immunostaining appeared in perikarya of optic nerve ganglion cells. In the anterior eye, no immunoreactivity was observed until P10. At P12-14, the cells of the epithelial layers of ciliary body and iris, as well as the cells of the trabecular meshwork and iris stroma, became immunoreactive for myocilin. At that time, positive staining for myocilin was also seen in the corneal endothelium and in keratocytes of the corneal stroma. An essentially similar staining pattern was seen in adult eyes. Northern blot analysis for myocilin mRNA in RNA from developing mouse eyes was negative until P9. At P12, a distinct band was observed. A band with similar mobility, but somewhat more intense, was detected in mRNA from adult mouse eyes 2-3 months of age. CONCLUSIONS: The onset of immunoreactivity for myocilin in the retina occurs in parallel with the maturation of optic nerve ganglion cells. In the anterior eye, the expression of myocilin is associated with the final development of those tissues that are directly involved in aqueous humor dynamics. The presence of myocilin might be important for proper function and structure of mature optic nerve ganglion cells and aqueous humor outflow.

Animals↗

Cyclodialysis ab interno as a surgical approach to intractable glaucoma.

PURPOSE: In glaucoma filtration surgery, the problem of subconjunctival scarring has still not been satisfactorily solved. Suprachoroidal drainage of aqueous humour offers a promising, alternative option for intractable glaucoma. We here present a clinical study on the surgical approach of gonioscopic cyclodialysis ab interno. PATIENTS AND METHODS: Twenty-eight eyes of 20 patients with intractable glaucoma were included in this prospective, consecutive, case-control study. The eyes had had a mean of 4.4 +/- 2.4 previous antiglaucomatous interventions. Baseline intraocular pressure (IOP) was 34.3 +/- 10.5 mmHg despite maximum therapy. Under gonioscopic control, cyclodialysis ab interno was performed over two clock times to gain access to the suprachoroidal space. No additional trabecular meshwork surgery was performed. Success was defined as a lowering of IOP to below 21 mmHg without the need for further medication or intervention. RESULTS: Mean postoperative IOP was 14.6 +/- 12.4 mmHg. Mean follow-up (FU) for all eyes was 121.8 days. After a mean of 60 days, 21 eyes (75%) needed further surgical intervention. Qualified success was seen in four eyes (14.3%), with a mean FU of 383.6 days. Three eyes (10.7%) showed absolute success after a mean FU period of 202.7 days. In our series, we obtained the best results for phakic eyes, followed by pseudophakic and aphakic eyes. CONCLUSION: The results of this study do not provide convincing evidence of the functional efficacy of cyclodialysis ab interno. Nevertheless, the technique is easy to perform and offers safe and atraumatic access to the resorptive capability of the choroid. Conjunctival manipulation is avoided. Contrary to reports in the current literature, in our series, the best results were obtained for phakic eyes, though the small number of eyes included does not allow reliable statistics. Further studies will need to focus on the use of different space-retaining substances or a widening of the cyclodialysis cleft to improve surgical outcome.

Adult↗

Transforming growth factor-beta: a growth factor inducing alpha B-crystallin expression in ciliary muscle cells.

BACKGROUND: In a recent study we showed that, in vitro, transforming growth factor-beta 2 (TGF-beta 2) induces alpha B-crystallin expression in cultured trabecular meshwork (TM) cells, but not in cultured fibroblasts. We assumed that alpha B-crystallin can be induced by TGF-beta 2 only if the cells are already expressing a basal level of the protein. In the present study we therefore treated cultured ciliary muscle (CM) cells constitutively expressing alpha B-crystallin and investigated the effect of TGF-beta on expression of alpha B-crystallin and the corresponding mRNA in these cells. MATERIAL AND METHODS: Monolayer cultures of third-passage CM cells from eyes of five human donors (12-73 years), being confluent for 7 days, were treated with 1.0 ng/ml TGF-beta 1 or TGF-beta 2. Induction of alpha B-crystallin and the related mRNA was investigated by immunofluorescence and by western and northern blot analysis. RESULTS: An increase in alpha B-crystallin mRNA was observed following treatment with TGF-beta. Actinomycin blocked the induction of alpha B-crystallin by the cytokine TGF-beta. Using western blotting the increase in alpha B-crystallin expression in CM cells was only small. CONCLUSION: These results confirm our assumption that induction of alpha B-crystallin by the cytokine TGF-beta depends on basal levels of the protein and its mRNA constitutively present within the cells. Comparison of the increase in alpha B-crystallin mRNA and protein expression indicate that post-transcriptional regulation mechanisms are responsible for these findings in CM cells.

Aged↗

The lens influences aqueous humor levels of transforming growth factor-beta 2.

BACKGROUND: Transforming growth factor-beta 2 (TGF-beta 2) is a pluripotent cytokine which has been suggested to play a number of roles in ocular physiologic and pathologic states. Intraocular fluid (i.o.f.) levels of TGF-beta 2 are quite high. Although the sources of ocular TGF-beta are not completely defined, the retinal pigment epithelium, the epithelium of the ciliary body and trabecular meshwork cells all secrete it. In this study we utilized canine lens and rabbit ciliary pigmented epithelial cell cultures to quantitate the in vitro secretion of TGF-beta 2. In addition, the effects of aphakia or the presence of cataractous lenses on IOF TGF-beta 2 levels were determined. METHODS: Lens and ciliary body epithelial cell culture supernatants and aqueous humors were assayed for total TGF-beta 2 levels by ELISA and bioassay. RESULTS: TGF-beta 2 accumulated in the media bathing lens epithelial cell cultures (0.7 +/- 0.03 ng/ml at day 2) and ciliary pigmented epithelial cell cultures (0.8 +/- 0.06 ng/ml at day 2) in a time-dependent manner. Surprisingly, aqueous humor from aphakic rabbit eyes contained significantly higher levels of TGF-beta 2 than their contralateral phakic controls. Furthermore, aqueous humor from canine eyes with cataracts also contained significantly higher levels of TGF-beta 2 than normal eyes. CONCLUSIONS: These results suggest that the lens secretes TGF-beta 2 and that the presence and status of the lens may influence IOF TGF-beta 2 levels.

Animals↗

Anterior segment changes in rabbits after experimental aqueous replacement with various amounts of different perfluorocarbon liquids.

BACKGROUND: We evaluated biomicroscopic and histological effects on the anterior segment in the rabbit eye after temporary aqueous substitution with various amounts (0.2 cc and 0.025 cc) of perfluorodecaline (PFD) and perfluorophenanthrene (PFP). METHODS: A quantity of 0.2 cc of the two perfluorocarbon (PFC) liquids was exchanged simultaneously with about 50% of the aqueous in 15 rabbit eyes each for periods of 1, 2, or 4 weeks. At these points some eyes were enucleated for histological examination. After 2 and 4 weeks the substances were removed from the remaining eyes, which were then followed up for 8-10 weeks. In an additional 8 eyes, 0.025 cc PFD or PFP was injected and left for 8 weeks. Four eyes received balanced salt solution and served as controls. Beside biomicroscopic evaluation and measurement of the intraocular pressure, endothelial cell counts and corneal pachymetry were performed regularly during follow-up. RESULTS: The postoperative results were well comparable for PFD and PFP eyes. Within the first 2 weeks postoperatively corneal edema with endothelial cell loss was observed in both groups. Thereafter regression of the edema started independently of whether the substances were removed or not. IOP was not elevated at any time. At the end of follow-up central corneal thickness was the same as initially. In the inferior corneal endothelium cell density decreased to 45-50% of that in normals. Histologically, vacuoles in the iris and chamber angle were found inferiorly after 4 weeks. Chamber angle closures were present between 5 and 7 o'clock in those eyes where the PFC liquids had been removed after 2 and 4 weeks. Eyes with 0.025 cc PFD or PFP droplets showed vacuolization of the inferior trabecular meshwork 8 weeks postoperatively that was comparable with eyes which had a 50% aqueous replacement for 4 weeks. Control eyes remained unchanged in all aspects. CONCLUSION: Anterior segment damage caused by PFC liquids is a contact-dependent effect seen in the early observation period. Experimentally there was no difference between the products used or between 2 and 4 weeks' duration of the tamponade.

Animals↗

Immunocytochemical localization of thrombomodulin in the aqueous humor passage of the rat eye.

This report describes the distribution and localization of thrombomodulin (TM) in the rat eye by light and electron microscopic immunocytochemistry. In addition to the endothelium of the entire vasculature, TM was found on the non-vascular structures lining the cavities of the posterior and anterior chambers and the limbus. TM was localized on the basal, lateral, and apical plasma membranes of the inner and outer ciliary epithelium, and the posterior iris epithelium in which there was no polarized expression of TM. In the anterior chamber, TM was localized on the luminal surface of the corneal endothelium, but was negative on the anterior border layer of the iris, which is composed of a discontinuous layer of fibroblasts and collagen fibers. Thus, TM was present at sites of cell-to-cell contact. TM was also present on the endothelia of the trabecular meshwork and the Schlemm's canal in the limbus. TM was localized not only on the luminal plasma membrane, but also on the cytoplasmic giant vacuoles in the endothelial cells of the Schlemm's canal. These findings extend the importance of anticoagulant mechanisms to the systems of secretion, circulation, and drainage of the aqueous humor.

Animals↗

Preliminary results of development of a single-mode Q-switched Nd: YAG ring laser at 213 nm and its application for the microsurgical dissection of retinal tissue ex vivo.

The Nd: YAG laser family offers wide possibilities for surgery applications in medicine. The radiation at 213 nm provides similar tissue effects as compared to 193 nm excimer lasers, but offers considerable practical advantages in the operating room. As such, it is of considerable interest to create single-mode Q-switched fifth harmonic Nd: YAG pulsed lasers with a high coefficient of efficiency and low divergence. Parameters of the ring three-mirror anisotropic cavity TEM00-Nd: YAG laser were calculated on the basis of the analysis of Gaussian beam behavior in the three-mirror ring cavity, with one convex spherical mirror and one intracavity positive lens. On the hand of numerical calculations a prototype of a single-mode Q-switched Nd: YAG-213 nm laser with an output energy of 4 mJ and a beam divergence of 1 mrad has been developed. At a pulse repetition rate of 50 Hz, it has a generation efficiency in the Q-switched mode of 0,6%. A hollow core wave guide is used in combination with a short length of a special fused silica optical fiber to guide the laser beam. Full-depth dissection of rabbit retina ex vivo was achieved at the intensities of 0.18-0.05 J/cm2 and a repetition rate of 50 Hz, with a linear cutting rate of 6 mm/s. Although the retina was completely cut, heat necrosis of the choroid did not occur. We are currently in the process of testing the dissection of retinal tissue during retinotomy, and the formation of holes in the trabecular meshwork in glaucoma surgery.

Animals↗

Bone tissue ablation with sub-microS pulses of a Q-switch CO(2) laser: histological examination of thermal side effects.

. The goal of this study is an in vitro evaluation of thermal side-effects by the application of short sub- micro s CO(2) laser pulses in combination with an air-water spray on different types of bone tissue. A mechanically Q-switched CO(2) laser delivered 300 ns pulses at 9.6 micro m wavelength, which were focused down to a spot size of 440 micro m on the tissue (a corresponding energy density of 9 J/cm(2)). Bone samples (blocks from pig femur, rib, or cartilage) were moved through the beam repeatedly until 1-5 mm deep cuts were produced. An air driven water spray was applied to prevent the tissue dehydration. Subsequent visual and histological examinations revealed no carbonisation, melting traces or fissuring of the tissue. An extremely narrow, 2-6 micro m thick thermally altered layer was observed at the cut border in compacta and cartilage. No accumulation of the thermal damage occurred with increasing cut depth. Laser incisions in trabecular tissue were accompanied with a 100-200 micro m thick zone of thermal necrosis in bone marrow. The difference from compacta and cartilage can be explained considering the particular character of the spreading of the ablation products in the trabecular meshwork. Minor thermal side effects make the Q-switched and probably other short pulsed CO(2) laser systems interesting for hard tissue surgery.

Animals↗

The histopathology of pigmentary dispersion syndrome with glaucoma.

Iris tissue and trabecular meshwork, obtained at time of trabeculectomy, was studied using the light and electron microscope in a 54-year-old woman with pigmentary dispersion syndrome with glaucoma. The specific defect was a loss of the outer epithelial cells of the iris with marked thinning of the remaining outer layers so that the two-cell architecture of the iris epithelium was maintained. In addition, the radial muscle layer was increased in both number and size of muscle fiber. It would appear that the pigmentary dispersion syndrome may represent a congenital or developmental abnormality of the iris epithelium, or both, and that the glaucoma which occasionally occurs in conjunction with this syndrome is of the usual open-angle type.

Atrophy↗

Ocular changes in epidermolysis bullosa letalis.

Ocular changes in a rare case of epidermolysis bullosa letalis included edema of the trabecular meshwork, ciliary body, lens, optic nerve, and formation of edema cysts in the iris. The retinal was completely detached and focally necrotic. Foci of necrosis and detachment of the retinal pigment epithelium were also observed with occasional breach in the Bruch's membrane. The choroid showed focal edema and congestion.

Autopsy↗

Protrusions of the inner wall of Schlemm's canal.

Large specific protrusions of the trabecular meshwork into Schlemm's canal (hernias) have been suggested to be the main drainage routes for aqueous humor, similar to the function of the arachnoid villi in draining the cerebrospinal fluid. My quantitative study in cynomolgus monkeys does not support such a hypothesis. The drainage routes of the aqueous humor, evaluated from the number and sizes of the pores observed by scanning electron microscopy, were as common through the hernias as through other parts of the inner wall of Schlemm's canal at different levels of intraocular pressure. The total surface of the hernias was a small percentage of the total surface of the inner wall.

Animals↗

Oculodentodigital dysplasia syndrome with angle-closure glaucoma.

A 14-year-old girl with typical oculodentodigital syndrome had been treated for chronic glaucoma for seven years. She had corneas measuring R.E.: 10 mm; L.E.: 9 mm, with narrow angles open on the right, but almost entirely closed on the left. Gonioscopic examination of the right iris revealed that the root was attached forward on the trabecular meshwork, which suggested a congenital anomaly. Peripheral iridectomies were ineffective. In a case previously studied, a 20-year-old woman with typical oculodentodigital syndrome developed typical acute angle-closure glaucoma seven years after the original examination.

Adolescent↗

Iris involvement in granulocytic sarcoma.

A 6-year-old boy with a diagnosis of acute myeoblastic leukemia in remission developed iris infiltration accompanied by uveitis, hypopyon, and vitreous hemorrhage, which was initially unilateral, later becoming bilateral. Pathologically, the eyes showed leukemic infiltrates in the conjunctiva, episclera, sclera, ciliary body, trabecular meshwork, canal of Schlemm, choroid, vitreous, and the iris. Leder stain studies showed positive esterase activity, indicating granulocytic sarcoma. Granulocytic sarcoma may appear intraocularly as iris nodules. These iris nodules may be the initial manifestation of granulocytic leukemia.

Antineoplastic Agents↗

Histopathologic and clinical associations of scleritis and glaucoma.

Of 92 enucleated eyes with scleral inflammation and 114 eyes from 81 patients with scleritis, 45 (49%) and 20 (18%), respectively, showed evidence of increased intraocular pressure. Damage to the trabecular meshwork of iridocyclitis, overlying corneoscleral inflammation, or peripheral anterior synechiae was the most common cause of increased intraocular pressure. Other causes included topical corticosteroid use, angle neovascularization, and posterior scleritis with secondary angle closure.

Adolescent↗

Photoreceptor outer segments in the aqueous humor in rhegmatogenous retinal detachment.

We treated seven patients (all male, ranging in age from 11 to 31 years) with Schwartz syndrome, a combination of uveitis, high intraocular pressure, and retinal detachment with peripheral tears. The condition was resistant to corticosteroids but responded well to surgery. Puncture of the anterior chamber disclosed many outer segments of the visual cells with few inflammatory cells in the aqueous humor in all seven patients. Possibly the outer segments, flowing from the subretinal space through the peripheral retinal break into the aqueous humor, cover the trabecular meshwork and cause the decrease in the coefficient of outflow. Detection of the outer segments led us to make a definite diagnosis and institute the appropriate treatment.

Adolescent↗