Aquaporins and ion conductance.
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Animals↗
Biomedical subjects
M B Wax
Publications and source records attributed to M B Wax.
Parapapillary chorioretinal atrophy in patients with ocular hypertension. I. An evaluation as a predictive factor for the development of glaucomatous damage.
OBJECTIVE: To determine whether parapapillary chorioretinal atrophy is a risk factor for the development of glaucomatous optic disc or visual field damage. METHODS: The initial morphometric parameters of the optic disc and parapapillary atrophy were retrospectively investigated in 350 eyes of 175 patients with ocular hypertension. The prognostic value of parapapillary atrophy at the baseline examination and its relationship with known risk factors for the development of glaucomatous damage were analyzed by multivariate analysis. RESULTS: Visual field loss, optic disc damage, or both were detected in 98 eyes of 53 patients during the follow-up period of at least 10 years. By univariate analysis, the presence of parapapillary atrophy, as well as higher parapapillary atrophy area-disc area, zone beta area-disc area, and parapapillary atrophy length-disc circumference ratios, at the baseline examination was associated with the conversion to glaucoma. In addition, higher intraocular pressure, larger vertical cup-disc ratio, and smaller neural rim area-disc area ratio at the baseline examination were associated with subsequent glaucomatous optic nerve damage. In a multivariate regression model adjusted for other factors, intraocular pressure (relative risk, 1.19), neural rim area-disc area ratio (relative risk, 0.72), and zone beta area-disc area ratio (relative risk, 1.32) were found to be associated with the development of optic disc damage, visual field damage, or both. CONCLUSION: The presence and the size of parapapillary atrophy are related to the development of subsequent optic disc or visual field damage in patients with ocular hypertension.
Choroid↗
Parapapillary chorioretinal atrophy in patients with ocular hypertension. II. An evaluation of progressive changes.
OBJECTIVE: To determine whether parapapillary chorioretinal atrophy in patients with ocular hypertension remained stationary or progressed along with glaucomatous optic nerve damage. METHODS: The morphometric parameters and progression of parapapillary atrophy were retrospectively investigated, using serial photographs, in 350 eyes of 175 patients with ocular hypertension. The association of parapapillary atrophy progression with subsequent glaucomatous conversion and with other baseline patient- and eye-specific characteristics was analyzed. RESULTS: Progression in the area and extension of parapapillary atrophy before noticeable optic disc or visual field changes was observed in 48 (49.0%) of 98 eyes that converted to glaucoma, while parapapillary atrophy progression was noted in 25 (9.9%) of 252 ocular hypertensive eyes that did not develop glaucomatous damage (P<.001). The predictive sensitivity and specificity of this observation were 49% and 90%, respectively. In a logistic multiple regression model, the progression of parapapillary atrophy was associated with a family history of glaucoma (odds ratio, 2.7) and the initial size of zone beta (odds ratio, 1.64, for an increase of 0.10 of the zone beta area-disc area ratio). CONCLUSION: The progression of parapapillary chorioretinal atrophy may be an early glaucomatous finding in some patients with ocular hypertension.
Choroid↗
Expression of aquaporins in the rat ocular tissue.
The aquaporins (AQPs) are a rapid growing family of water channel proteins found in animals, plants and microorganisms that raise plasma membrane water permeability required for efficient isosmotic fluid transport. Five homologs of aquaporins (AQP1, AQP2, AQP3, AQP4 and AQP5) have been identified from various mammalian tissues; the expression of these aquaporins in ocular tissues was studied. Semiquantitative expression levels of these aquaporins were determined in ciliary body, cornea, lens, retina, iris and choroid using RT-PCR. Expression levels of AQP1 are highest among the known aquaporins in each rat ocular tissue examined. In cornea, AQP1 is expressed approximately three-fold higher than AQP3 and 2.5 fold higher than AQP5. However, the highest intraocular expressions of AQP3 and AQP5 are in the cornea. In the iris, expression levels of AQP1 are approximately 600-700 fold higher than AQP4 and AQP5. In the ciliary body, the expression levels of AQP1 are approximately ten-fold higher than AQP4, the only other aquaporin expressed. In the lens, the major water channel is AQP1 with detectable levels of AQP4 and AQP5 that are approximately 1000-fold lower than AQP1. In choroid, AQP1 is the only water channel expressed. In retin, AQP1 is expressed approximately six-fold higher than AQP4, the only other aquaporin expressed. However, the highest ocular expression of AQP4 is in retina. AQP2 is not detected in the eye. Finally, the possible physiological roles of aquaporins in maintaining and regulating the aqueous flow, and corneal and lens transparency are discussed.
Animals↗
Plasma and aqueous humor endothelin levels in primary open-angle glaucoma.
PURPOSE: Endothelins (ET) have some effects on the regulation of aqueous humor dynamics. To investigate their possible role in glaucoma, we measured plasma and aqueous humor ET levels in patients with and without primary open-angle glaucoma. METHODS: Plasma and aqueous humor samples were obtained from 31 patients with primary open-angle glaucoma and 24 patients without glaucoma. Measurements were made by radioimmunoassay (RIA) for ETs with the following cross-reactivities: ET-1, ET-2, and big ET-1, 100%; and ET-3, 70%. RESULTS: The ages (mean +/- SD) of the patients with primary open-angle glaucoma (72.3 +/- 10 years) and normal subjects (72.8 +/- 8 years) were similar (p = 0.92). There was no significant difference between plasma ET levels of the two groups (p = 0.07). However, aqueous humor ET levels (mean +/- SD) were higher in the primary open-angle glaucoma group (44.26 +/- 2.6 pg ml-1) than in normal subjects (42.17 +/- 1.6 pg ml-1) (p = 0.001). The ratios of corresponding aqueous humor to plasma levels of ETs were approximately 10% higher in the primary open-angle glaucoma group (3.76) than in normal subjects (3.41) (p = 0.0002). CONCLUSIONS: The small increase in aqueous humor endothelin levels in patients with primary open-angle glaucoma versus controls of similar age may be relevant to the understanding of the various roles of ETs in aqueous humor dynamics in these patients.
Aged↗
Primary valve malfunction of the Krupin eye valve with disk.
PURPOSE: To examine the management and possible causes of primary valve malfunction of the Krupin eye valve with disk. METHODS: The authors reviewed the results of 113 patients undergoing implantation of the Krupin eye valve with disk and identified eight patients with primary valve malfunction requiring surgical revision. RESULTS: Valve revision involved manipulation (n = 1 case), explantation of the malfunctioning valve and implantation of a new valve (n = 2), and amputation of the valve (n = 5). Six of eight patients had final intraocular pressures of < 21 mmHg on one or no medications at a mean interval of 15.9 months (range 5-36) after surgical revision. Transient postoperative hypotony was noted in three patients and chronic hypotony with loss of light perception in one patient. One explanted valve was examined and found to have partially fused leaflets. CONCLUSIONS: Surgical revision in cases of primary valve malfunction of the Krupin eye valve with disk may be accomplished relatively safely with an acceptable level of postoperative complications. The etiology of primary valve malfunction may be related to the sterilization process and prolonged storage before implantation.
Filtering Surgery↗
Comparative results of combined procedures for glaucoma and cataract: I. Extracapsular cataract extraction versus phacoemulsification and foldable versus rigid intraocular lenses.
BACKGROUND AND OBJECTIVES: The refinements of small-incision cataract surgery by phacoemulsification with foldable intraocular lens (IOL) implantation have recently permitted new options for combined trabeculectomy with cataract extraction. The objectives of this study were to compare the long-term intraocular pressure (IOP) control and visual outcome between trabeculectomies combined with extracapsular cataract extraction (ECCE) versus those with phacoemulsification, and to analyze these same factors for foldable versus rigid IOLs. PATIENTS AND METHODS: The authors retrospectively reviewed the charts of 311 patients (397 eyes) who underwent combined trabeculectomy with cataract extraction and posterior chamber IOL implantation. In all of the surgeries, releasable scleral flap sutures were used. The mean follow-up was 22.9 +/- 15.1 months, with a minimum follow-up of 12 months. RESULTS: Trabeculectomy combined with phacoemulsification had a lower postoperative complication rate and was more effective than trabeculectomy combined with ECCE in reducing IOP to less than 20 mm Hg with or without medication (95% vs 82%) and in improving vision to levels of 20/40 or better (71% vs 52%) (P < .001). Regarding IOLs, foldable silicone lenses were found to be an effective alternative to polymethylmethacrylate lenses in combined surgeries in terms of a controlled IOP of less than 20 mm Hg (97% vs 97%) and visual recovery to 20/40 or better (78% vs 63%). CONCLUSION: The combination of trabeculectomy with releasable scleral flap sutures and small incision cataract surgery with foldable IOL implantation has improved postoperative IOP control and visual rehabilitation.
Aged↗
Comparative results of combined procedures for glaucoma and cataract: II. Limbus-based versus fornix-based conjunctival flaps.
BACKGROUND AND OBJECTIVE: One of the variables to be considered in a combined procedure for glaucoma and cataract is the type of conjunctival flap to be used. The objective of this study was to compare the effects of limbus-based and fornix-based conjunctival flaps on postoperative long-term intraocular pressure (IOP) control and visual acuity after combined trabeculectomy with phacoemulsification. PATIENTS AND METHODS: The authors retrospectively reviewed the charts of 189 patients (215 eyes) who underwent combined trabeculectomy with phacoemulsification, posterior chamber intraocular lens (IOL) implantation, and intraoperative mitomycin-C administration and who had a minimum follow-up of 12 months. The results of the limbus-based (151 eyes) versus fornix-based (64 eyes) conjunctival incisions used in these combined procedures were compared. RESULTS: In the limbus-based conjunctival flap group, 146 eyes (97%) achieved an IOP of less than 20 mm Hg, with or without medication; 62 eyes (97%) of the fornix-based conjunctival flap group (P > .05) achieved this result. A visual acuity of 20/40 or better was noted in 106 eyes (70%) in the limbus-based conjunctival flap group and in 45 eyes (70%) in the fornix-based conjunctival flap group (P > .05) at the last examination. Early wound leakage was observed more frequently in the fornix-based conjunctival flap group (8% vs 1%) (P = .014); however, it was not a serious clinical problem, as only 1 eye required surgical repair. Posterior capsular opacification was found more often in the limbus-based conjunctival flap group (25% vs 14%) (P = .072) and required more frequent laser capsulotomy (22% vs 9%) (P = 0.03). CONCLUSION: Limbus-based and fornix-based conjunctival flaps appear to be comparable with respect to postoperative IOP control and visual acuity after a combined trabeculectomy with phacoemulsification and posterior chamber IOL implantation in cases supplemented by intraoperative mitomycin-C.
Administration, Topical↗
Comparative optic disc analysis in normal pressure glaucoma, primary open-angle glaucoma, and ocular hypertension.
PURPOSE: The authors wished to determine whether characteristics of optic disc and parapapillary atrophy differ between eyes with ocular hypertension, primary open-angle glaucoma (POAG) and those with normal-pressure glaucoma, including a subset of patients with normal-pressure glaucoma with evidence of serum abnormalities of humoral autoimmunity. METHODS: Three hundred ninety-two eyes of 196 patients with ocular hypertension, 394 eyes of 197 patients with POAG, and 135 eyes of 68 patients with normal-pressure glaucoma were analyzed. Nerve fiber layer hemorrhage in the optic disc region, retinal arteriolar narrowing, and morphometric parameters of optic disc and parapapillary atrophy were investigated in these groups. Parapapillary atrophy was differentiated in two different zones (alpha and beta). RESULTS: Nerve fiber layer hemorrhage and arteriolar narrowing were found more frequently in patients with normal-pressure glaucoma than in patients with POAG (P = 0.014, P = 0.004) and ocular hypertension (P < 0.0001, P < 0.0001). Zone beta was detected more often in patients with normal-pressure glaucoma than in those with ocular hypertension (P < 0.001) and POAG (P = 0.013). Although patients with normal-pressure glaucoma had more advanced neural rim loss and larger parapapillary atrophy, there were similar correlations between neural rim area and the area and extension of parapapillary atrophy in patients with normal-pressure glaucoma and POAG. Parapapillary atrophy parameters also were similar in different stages of neural rim damage in patients with normal-pressure glaucoma and POAG (P > 0.05). Optic disc characteristics were not different (P > 0.05) between the subgroups of patients with normal-pressure glaucoma. CONCLUSION: The authors' findings support the idea that besides the enlargement of the area and extension of parapapillary atrophy that accompanies neural damage in glaucoma, the severity of the parapapillary atrophy also increases as assessed by the increase in zone beta in more damaged eyes. Furthermore, the final clinical appearance of optic nerve damage is similar among patients with POAG, normal-pressure glaucoma, and the subgroups of normal-pressure glaucoma, regardless of their possibly different mechanisms of neuropathy.
Aged↗
Anti-rhodopsin antibodies in sera from patients with normal-pressure glaucoma.
PURPOSE: To explore further the potential role autoimmunity may play in the pathogenesis of normal-pressure glaucoma (NPG) in some patients, the authors examined the sera of patients with NPG for the presence of antibodies directed toward retinal antigens. METHODS: Using patient sera, immunoblotting was performed on subcellular fractions of retina, purified bovine rhodopsin, and immunoaffinity-purified recombinant human rhodopsin. A chemiluminescence-enzyme-linked immunosorbent assay (ELISA) to detect anti-rhodopsin antibodies was developed and used. RESULTS: A patient with NPG was found to have a high titer of immunoglobulin M-lambda antibody against a 40-kd retina-specific glycoprotein antigen subsequently identified as rhodopsin. ELISA analysis conducted on sera from 28 patients with NPG and 26 patients with primary open-angle glaucoma (POAG) revealed highly significant differences in anti-rhodopsin antibody activity between these groups (P < 0.0002, Mann-Whitney test). For example, the majority of patients with NPG (19/28; 68%) had anti-rhodopsin antibody activity higher than the highest value obtained from among 26 age-matched patients with POAG. CONCLUSIONS: An elevated anti-rhodopsin antibody count is related to NPG. This may indicate that there is an autoimmune component in the optic neuropathy in these patients. The specific role of these autoantibodies, if any, in the pathogenesis of the disease remains to be determined.
Aged↗
Cloning of a novel cDNA homologous to CHIP28 water channel from ocular ciliary epithelium.
Water channel protein (CHIP28) has been initially identified from human erythrocyte and subsequently localized in human kidney, rat kidney and bovine corneal endothelium. We report here cloning of homologous cDNA (CHIP29) from an expression cDNA library constructed from bovine ciliary epithelium poly A+ that codes a 271 amino acid, 28.8 kDa protein. At the amino acid level, bovine CHIP29 is 91% identical to the CHIP28 protein. Analysis of the deduced amino acid sequence indicated a hydrophobic protein with six membrane spanning domains, one N-linked glycosylation site, two conserved NPA boxes common to MIP26 family proteins, and conserved amino acid residue cysteine 189 common to water channels. Northern blotting revealed a major mRNA of 2.8 Kb size expressed in bovine ciliary epithelium. The results presented here confirm the presence of water channel gene in the bovine ciliary epithelium, a primary site for the aqueous humor production.
Amino Acid Sequence↗
Increased incidence of paraproteinemia and autoantibodies in patients with normal-pressure glaucoma.
We assessed the incidence of paraproteins and autoantibodies in 44 patients (mean age, 65.3 +/- 1.9 years) with normal-pressure glaucoma and 41 patients (mean age, 68.8 +/- 1.8 years) monoclonal proteins occurred more often (P = .0047) in patients with normal-pressure glaucoma (eight of 44, 18%) than in control subjects with primary open-angle glaucoma (zero of 41, 0%). Autoantibodies to extractable nuclear antigens, most often Sjögren's syndrome A antigen (SSA[Ro]), were also found more frequently (P = .0022) in patients with normal-pressure glaucoma (13 of 44, 30%) than in control subjects (one of 41, 2%). Paraproteins and autoantibodies to extractable nuclear antigens generally occurred in different patients with an overall incidence of 20 of 44 (45%) patients with normal-pressure glaucoma. In contrast, no significant difference in the incidence of antinuclear antibodies existed between the groups. These findings suggest that humoral immune mechanisms may have a role in the pathogenesis of optic neuropathy in patients with normal-pressure glaucoma.
Adult↗
Immunoprecipitation of A1 adenosine receptor-GTP-binding protein complexes in ciliary epithelial cells.
PURPOSE: To examine the interaction of alpha subunits of guanine nucleotide binding proteins with A1 adenosine receptors from the SV40-transformed bovine-derived pigmented (PE) and human-derived nonpigmented (NPE) ciliary epithelial cell lines using an immunoprecipitation approach and [3H]DPCPX, a selective radioligand to adenosine receptor. METHODS: Solubilized preparations of adenosine receptors from PE and NPE cell lines were immunoprecipitated with G protein specific antisera 8730 (anti-Gi alpha), 3646 (anti-Gi alpha 1), 1521 (anti-Gi alpha 2), and 1518 (anti-Gi alpha 3), and of adenosine receptor-G protein complexes were detected by the binding of radioactive [3H]DPCPX. RESULTS: Data indicate that [3H]DPCPX forms high-affinity complex with membrane-bound and solubilized forms of adenosine receptors from PE and NPE cells. Peptide-directed antisera against various G protein alpha subunits indicate that the A1 adenosine receptors from these cells are specifically coupled to Gi alpha complexes. The results further indicate that the A1 adenosine receptors are predominantly associated to Gi alpha-3. CONCLUSION: The findings document a selective interaction between the alpha subunits of the inhibitory guanine nucleotide binding protein (Gi) and A1 adenosine receptors in ocular ciliary epithelial cells in culture. The results suggest that adenosine receptors coupled to Gi alpha-3 may provide a site at which modulation of aqueous humor production in the ciliary epithelium occurs via the G protein-adenylyl cyclase pathway.
Animals↗
Optic nerve sheath decompression for glaucomatous optic neuropathy with normal intraocular pressure.
OBJECTIVE: To report our therapeutic experience with optic nerve sheath decompression in patients with normal-pressure glaucoma. DESIGN: A case series of seven eyes from six patients with glaucoma and normal intraocular pressures who continued to have progressive visual field loss despite conventional therapy. SETTING: A hospital-based, referral glaucoma service. PATIENTS: Three men (67, 67, and 72 years of age) and three women (58, 61, and 70 years of age). INTERVENTIONS: Optic nerve sheath decompression. MAIN OUTCOME MEASURES: Visual field data and visual acuity measurements were obtained at regular intervals during the postoperative periods (range, 3 to 18 months). RESULTS: Two of seven eyes from six patients appear to have enjoyed an initial significant improvement in their visual fields with improved visual acuity in one eye of one patient. The visual fields, however, appear to have deteriorated 18 months after the initial procedure in these two patients. In the remaining four patients, no further improvement or deterioration was observed within a limited follow-up period. CONCLUSIONS: The transient improvement in the visual fields of one eye from each of two patients documents an initial successful use of optic nerve sheath decompression in patients with nerve fiber bundle damage in the absence of optic nerve head swelling. However, the long-term potential of optic nerve sheath decompression in these patients may be of limited value.
Aged↗
Does dopamine act at dopamine receptors in the ciliary epithelia?
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Adenylyl Cyclases↗
Regulation of adenylyl cyclase in rabbit iris ciliary body.
The enzyme adenylyl cyclase has been shown to be important in the regulation of intraocular pressure. We therefore studied the activity of adenylyl cyclase (AC) activity in the rabbit iris/ciliary body (I/CB) after pre-treatment with the beta-adrenergic agonist isoproterenol (ISO) which activates cAMP dependent protein kinase A, and phorbol 12,13 dibutyrate (PDB) which activates protein kinase C. When I/CB was pre-treated with ISO (10 microM) or PDB (1 microM), attenuated AC activity (approximately 35%) resulted when the activity of the enzyme was assessed by rechallenge with isoproterenol. However, when AC activity was assessed by rechallenge with forskolin or prostaglandin, enhanced activity resulted. In an effort to identify the mechanism of this apparent heterologous regulation of AC, studies were performed that showed no significant changes in the density of beta-adrenergic receptors or the affinity of the receptors for the ligand (125I)-Iodopindolol occurred in ISO or PDB treated tissue. Similarly, in membranes prepared from ISO or PDB treated tissue, no significant changes in the functional activity of the guanine nucleotide binding proteins Gi or Gs could be ascertained as assessed by somatostatin inhibition of forskolin-stimulated AC (to assess Gi function), or in an adenylyl cyclase complementation assay (to assess Gs function). However, AC activity stimulated by Mn2+ and purified Gs was enhanced (approximately 2X) following isoproterenol or phorbol ester pre-treatment, suggesting that an alteration at the level of the catalytic subunit of AC resulted from ISO or PDB pretreatment. Therefore, the assessment of net changes in receptor coupled AC activity induced by phorbol esters or isoproterenol appears to be dependent on the drug used to rechallenge the AC system and cAMP production is dependent on the sum of diverse effects on multiple components of the AC pathway.
Adenylyl Cyclases↗
Distinct profiles of phosphodiesterase isozymes in cultured cells derived from nonpigmented and pigmented ocular ciliary epithelium.
Alterations in either cyclic AMP (cAMP) or cyclic GMP (cGMP) may modulate the production of aqueous humor by the ciliary epithelium of the eye, thereby affecting intraocular pressure. We have found distinct profiles of phosphodiesterase (PDE) isozyme activity in cultured cells derived from bovine pigmented ciliary epithelium (PE) and cells derived from human nonpigmented ciliary epithelium (NPE), as well as corresponding differences in the effects of selective PDE inhibitors on the accumulation of cAMP and cGMP. In NPE cells, but not in PE cells, the major peak of PDE activity was stimulated by Ca++/calmodulin-stimulated (PDE I), and hydrolyzed both cAMP and cGMP. In contrast, PE cells contained a cGMP-specific PDE V not found in NPE cells. Rolipram, a selective inhibitor of PDE IV, was more potent and effective than the selective PDE III inhibitor CI-930 at potentiating intracellular cAMP accumulation in both cell types. Zaprinast, a selective inhibitor of PDE V, potentiated cGMP accumulation in PE but not in NPE cells. The results suggest that selective PDE inhibitors may modulate aqueous humor production by pigmented and nonpigmented ciliary epithelium, the two cell types may have different functional roles, and selective modulation of their functions may be possible. Furthermore, there may be distinct roles for intracellular calcium in regulating cGMP and cAMP in pigmented vs. nonpigmented ciliary epithelial cells.
3',5'-Cyclic-AMP Phosphodiesterases↗
Effects of adrenergic agents on transepithelial electrical measurements across the isolated iris-ciliary body.
Transmembrane electrical measurements were performed on the isolated rabbit iris-ciliary body to study direct effects of adrenergic drugs on the ciliary epithelium. Alpha-adrenergic agonists (epinephrine, norepinephrine, or phenylephrine) lowered the short-circuit current (SCC) in a dose-dependent fashion relative to which chamber side the drug was added: simultaneous addition to both chambers greater than blood side only greater than aqueous side only. Pretreatment (5 x 10(-5) M) with the non-selective beta-adrenergic antagonist timolol had no effect while the non-selective alpha-adrenergic antagonist, phentolamine, completely prevented the alpha agonist-induced decrease in SCC. The alpha-adrenergic response was mediated by the alpha 1 subtype since prazosin, but not yohimbine, blocked the induced reduction in SCC. The beta-adrenergic agonist isoproterenol caused a dose-dependent decrease in the SCC. The decrease was similar when the drug was added to only the blood side or to both sides of the chamber. Addition to only the aqueous chamber had no effect. Pretreatment with beta-adrenergic antagonists blocked the isoproterenol response: non-selective = selective beta 2 greater than selective beta 1. The isoproterenol-induced decrease in SCC was also blocked by non-selective alpha-adrenergic antagonists. The response was mediated by the alpha 1 subtype since prazosin, but not yohimbine, blocked the isoproterenol response. This suggests that isoproterenol interacted with the alpha 1-adrenergic sensitive pathway in the rabbit ciliary process.
Animals↗