ISSN:0271-3683    

DOI:10.3109/02713689309024619

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The effect of ethacrynic acid, a potential outflow agent for the treatment of glaucoma, was studied in a series of 25 pairs of human eyes in perfusion organ culture.Concentrations varied from 0.01 mM to 2.4 mM and were used in single or repetitive doses.Intraocular pressure was continuously recorded for up to two weeks after exposure. Eyes were then fixed and the meshwork examined histologically.Ethacrynic acid in single doses of 0.05 mM, 0.3 mM, and 0.6 mM increased facility of outflow at least 40% when compared with fellow control eyes. The duration of effect was approximately 18 hours, during which time the intraocular pressure gradually returned to baseline. Histologic examination revealed dose related effects on the trabecular cells, ranging from clumping of nuclear chromatin in some eyes to cellular swelling, disruption of cytoplasmic membranes, and cell necrosis in other eyes at concentrations of 0.1 mM and higher. No recovery or reversal of these changes was noted with time, even two weeks after a single exposure to the drug. Although ethacrynic acid is effective in temporarily lowering intraocular pressure in the human eye, a low therapeutic index may limit its clinical usefulness.

ISSN:0271-3683    

DOI:10.3109/02713689309024620

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

5-Fluorouridine (5-FUR), a ribonucleotide metabolite of 5-Fluorouracil (5-FU), is a more potent inhibitor of cellular proliferation and cell-mediated contractionin vitrothan 5-FU. We compared the efficacy of these two drugs in a cell injection model of proliferative vitreoretinopathy using New Zealand albino rabbits. Forty-five eyes were divided into three groups and injected intravitreally with homologous fibroblasts. Eyes were examined at the time of injection and 7, 14, 21 and 28 days thereafter. By day 28, 70.5% (12 of 17) of 5-FUR treated eyes demonstrated no appreciable proliferative or tractional activity compared with 41.7% (5 of 12) of 5-FU treated eyes and 10% (1 of 10) of control eyes (p<0.006). Medullary ray puckers developed in 29.4% (5 of 17) and 25% (3 of 12) of 5-FUR and 5-FU treated eyes respectively. No 5-FUR treated eye developed extensive tractional or combined tractional and rhegmatogenous retinal detachment compared with 33.3% (4 of 12) of 5-FU treated eyes and 80% (8 of 10) of control eyes (p<0.001). These results suggest that 5-Fluorouridine may be more effective than 5-FU for the treatment of vitreoretinal scarring.

ISSN:0271-3683    

DOI:10.3109/02713689309024621

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Incubation of cultured bovine lens epithelial cells (BLECs) in minimal essential medium (MEM) containing 40 mM galactose for 20 hr results in an attenuation of3H-myo-inositol (3H-MI) concentrating ability. Decreased MI uptake could negatively impact on normal phospho-inositide turnover and diacylglycerol production, and presumably, protein kinase C (PKC) activation. The present report examines the relationship between PKC activity, myo-inositol transport and hyperglycemic conditions. PKC activities in the cytosol and particulate fractions of bovine lens epithelial cells in culture were quantitated using a mixed micelle assay following DEAE-cellulose (DE52) and Sephadex G-25 chromatography. Protein kinase C activity was assessed as Ca2+and phospholipid-dependent Ac-myelin basic protein substrate peptide phosphorylation and confirmed using a PKC pseudosubstrate inhibitor peptide (PKC 19–36). Total PKC activity was similar in galactose-incubated cells (871±64 pmol/mg total protein/min) and control cells (881±8 pmol/mg total protein/min) after 20 hr. In unstimulated cells, approximately 90% of the total cellular PKC activity was recovered in the cytosolic fraction. Enzyme translocation was induced with the tumor promoting phorbol ester, phorbol 12-myristate 13-acetate (PMA), resulting in a 6-fold increase in membrane-associated PKC activity. A similar PMA-induced translocation was observed in BLECs incubated with 40 mM galactose MEM-maintained cells briefly treated with PMA or the non-phobol PKC activators, SC-10 and mezerein, displayed a rate of3H-MI uptake similar to the untreated control cells. Treatment of galactose-incubated cells with any of the three PKC activators failed to alter the galactose-attenuated3H-MI accumulation. These observations demonstrated the presence of a Ca2+and phospholipid-dependent PKC activity in BLECs that appeared to function equally well in acute hyperglycemic conditions (20 hr) as in cells maintained in physiological medium. Moreover, these studies indicated that MI transport was not regulated directly by PKC and the galactose-induced attenuation in3H-MI-concentrating capability was not a consequence of a derangement in PKC activity under these incubation conditions.

ISSN:0271-3683    

DOI:10.3109/02713689309024622

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

In primates, ciliary muscle contraction causes accommodation and facilitates aqueous outflow. In living rhesus monkeys, accommodative, outflow facility, and ciliary muscle movement responses to cholinergic agonists all decline with age. We developed an apparatus to determine in vitro whether the latter is related to intra- or extra-ciliary muscle factors, and whether ciliary muscle contraction in the coronal (putatively more accommodation-relevant) and longitudinal (putatively more facility-relevant) vectors can be dissociated pharmacologically.In fresh ciliary muscle strips, carbachol and aceclidine each induced dose-dependent contraction in the longitudinal and coronal vectors. With neither drug was there any apparent dissociation of the responses in the two vectors. Atropine pretreatment completely prevented a supramaximal dose of carbachol from inducing ciliary muscle contraction in either vector.Ciliary muscle strips responded to several cholinergic agonists as well on day 2 (24–32 hours post-enucleation) as on day 1 (1–9 hours post-enucleation) when kept in a cell culture medium at 4°C. By light microscopy, the general architecture of the ciliary muscle, the muscle bundles, and the single muscle cells appeared normal; however, cellular and nuclear swelling were apparent following the 32-hour culturing period.Contractile responses to near-maximal doses of carbachol and aceclidine did not vary markedly with age in either vector, suggesting that the age-related decrease in ciliary muscle mobility in vivo is due to extra-muscular restrictive factors rather than diminished muscular contractility.

ISSN:0271-3683    

DOI:10.3109/02713689309024623

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

In recent years, there has been renewed interest in the association between DNA damage to the lens epithelium and the development of lens opacities. Although a number ofin vitrostudies have indicated that lens epithelial cells are susceptible to a variety of DNA damaging insults and that these cells posess the capacity to repair such damage, no previous studies have directly addressed whether DNA damage is associated with human cataractin vivo. Utilizing samples of lens epithelial cells obtained from patients undergoing cataract surgery, the percentage of cells containing DNA single strand breaks was directly determined by the single-cell gel assay (SGA) method. Non-cataractous human Eye Bank lenses of similar ages to the cataractous samples and calf lenses were used as controls. In approximately 50% of the cataractous samples analyzed, the proportion of cells containing DNA single strand breaks was significantly higher than in control lenses. No relationship between age and DNA damage was noted. These findings are consistent with the hypothesis that in some human patients with cataract, DNA damage in the lens epithelial cell population may be related to the development of lens fiber cell opacity.

ISSN:0271-3683    

DOI:10.3109/02713689309024624

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

The distribution of glutathione-S-transferase (GST) activity was determined in frozen normal human lenses. The highest activity of GST was found in the peripheral and equatorial regions, whereas the lowest activity was found in the nucleus. Western blot showed that bothμandχisoenzymes of GST were present in human lenses. This result is similar to that found in rat lenses. In addition, GST activity was analyzed in 50 lens epithelia which were obtained during cataract surgery. Twenty-seven lens epithelia showed no activity. Statistically significant association was found between cortical and mixed cortical-nuclear cataract and loss of GST activity. No association was found between pure nuclear cataract and loss of epithelial GST activity.

ISSN:0271-3683    

DOI:10.3109/02713689309024625

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Carbachol-stimulated release of inositolphosphates (IP) was studied in the whole retina from Long-Evans rats of different ages (day 5, 10, 15, 20, adult) followingin vitroincorporation of [3H]myo-inositol. Unlike the albino rat retina, the pigmented retina was highly light-sensitive, making it necessary to dark adapt the animals and perform retinal dissections under low illumination to prevent light-induced IP release. Retinae from postnatal day 10 rats showed the highest amount of carbachol-stimulated IP released. This response to carbachol decreased with age until postnatal day 20 when it reached adult levels. The pigmented rat retina showed a sharp fall in the degree of carbachol (1 mM)-stimulated IP released at the time of eye-opening (450% above basal in retinae from 10 day old animals, as compared to 230% above basal in 15 day old retinae). Basal release of IP was not altered in the retina during development. Muscarinic cholinergic receptor density was, however, found to increase 5 fold with age, reaching adult levels by PND 20. Retinal weight and protein per retina also increased (four fold) from day 5 to adult; however, thein vitroincorporation of [3H]myo-inositol into phosphoinositides (calculated as per mg protein) did not change during development. Thus, in animals prior to eye opening, a much higher proportion of phosphoinositides appears to be hydrolyzed upon muscarinic receptor stimulation. During retinal development a change in sensitivity to the agonist-sensitive pool(s) of phosphoinositides may occur and/or there may be alterations in the efficacy of receptor coupling to the second messenger system resulting in the disassociation observed between the drastic increase in receptor number and the apparent decrease in receptor-stimulated release of IP.

ISSN:0271-3683    

DOI:10.3109/02713689309024626

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

Dexmedetomidine is a selective alpha2- adrenoceptor agonist which has previously been shown to reduce the ocular pressure of normotensive rabbits as well as those with pressures artificially elevated by laser irradiation. In this study instillation of an equivalent hypotensive dose (12.5μg) did not cause changes in heart rate, blood pressure, blood glucose or plasma catecholamine content even though dexmedetomidine could be detected in plasma. However, this dose given intravenously (i.v.) was also without effect. Higher ocular doses resulted in equivalent bradycardia and changes in blood glucose levels as when the dose was given i.v. These two parameters proved to be most sensitive indicators of systemic alpha2-agonism, blood pressure did not change and plasma catecholamine levels were too low to be reliably assayed. It is concluded that when hypotensive doses of dexmedetomidine are instilled into the eye, intraocular concentrations are sufficiently high to exert pharmacological effects. As it is absorbed into the general circulation, it is diluted such that its systemic effects are minimal.

ISSN:0271-3683    

DOI:10.3109/02713689309024627

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor

摘要:

To study the role of the host inflammatory response inPseudomonas aeruginosakeratitis, rabbits were made leukopenic with intravenous injections of cyclophosphamide and dexamethasone. Twenty-four hr later, keratitis was initiated in all rabbits with an intrastromal injection of 1,000 log phase P. aeruginosa strain 27853. Slit lamp examination of eyes showed that leukopenic rabbits had significantly less (P<0.0001) ocular pathology at 16, 22, and 27 hr postinfection. The number of viable bacteria recovered from corneas of leukopenic rabbits was the same as the number recovered from nonleukopenic rabbits (P=0.95). These results suggest that the host inflammatory response significantly contributes to the overall ocular pathology associated with P. aeruginosa keratitis, but does not influence the survival of the infecting organism in the cornea at the height of the infection.

ISSN:0271-3683    

DOI:10.3109/02713689309024628

出版商:Taylor&Francis    

年代:1993

数据来源: Taylor