RESUMEN
PURPOSE: Fibroblast growth factor 2 (FGF-2) is not only a potent mitogen, it is a modulator for corneal endothelial cells. To define how the modulation activities of FGF-2 are mediated, we used pharmacologic inhibitors to examine the association of phospholipase C-gamma 1 (PLC-gamma) with FGF receptor or with cytoskeleton. METHODS: Cell proliferation was determined either by the incorporation of 3H-thymidine into DNA or by counting cell numbers in the absence or presence of the inhibitors. The protein expression was analyzed by immunoprecipitation and immunoblot analysis. Cell shape change was determined by phase-contrast microscopy. RESULTS: FGF-2 stimulated DNA synthesis, whereas genistein inhibited the FGF-2-mediated cell proliferation in a dose-dependent manner, regardless of the concentration of FGF-2. The PLC-gamma 1 specific antisense oligonucleotide primer was able to inhibit cell proliferation by 25% in the absence of FGF-2; however, the antisense primer was not able to override the action of FGF-2. Fibroblast growth factor receptor was phosphorylated on treatment of the cells with FGF-2; however, 24-hour treatment with the growth factor significantly reduced phosphorylation of the receptor. Phospholipase C gamma 1 appears to be abundant in cytoplasm in the absence and presence of FGF-2, and a minor portion of the molecule is translocated to membrane after treatment with FGF-2; genistein inhibited the translocation. When the cytoskeleton fraction of the normal and the modulated corneal endothelial cells was immunoprecipitated with PLC-gamma 1 antibodies, PLC-gamma 1, actin, and vinculin were coprecipitated in both cell cultures. Phospholipase C gamma 1 associated with cytoskeleton was phosphorylated on treatment of the cells with FGF-2. In the presence of FGF-2 of the modulated cells, cytochalasin B, which did not revert the modulated cell morphology, abolished the association of PLC-gamma 1 with actin and vinculin; colchicine, which did revert the modulated cell shape to the polygonal shape, did not block the association of these three molecules. Interestingly, colchicine slightly enhanced the stimulatory effect of FGF-2 on corneal endothelial proliferation in contrast to the effect of cytochalasin B, which slightly decreased the FGF-2 action on cell proliferation. CONCLUSIONS: The association of PLC-gamma 1 with cytoskeleton plays a role in cell proliferation, whereas the association of PLC-gamma 1 with actin and vinculin has no effect on cell shape changes. These findings indicate that FGF-2 appears to use distinct signaling pathways for cell proliferation and cell shape changes in corneal endothelial cells.
Asunto(s)
Endotelio Corneal/fisiología , Factor 2 de Crecimiento de Fibroblastos/fisiología , Transducción de Señal , Animales , División Celular/efectos de los fármacos , División Celular/fisiología , Tamaño de la Célula/efectos de los fármacos , Tamaño de la Célula/fisiología , Células Cultivadas , ADN/biosíntesis , Replicación del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Endotelio Corneal/citología , Factor 2 de Crecimiento de Fibroblastos/efectos de los fármacos , Factor 2 de Crecimiento de Fibroblastos/farmacología , Genisteína , Inhibidores de Crecimiento/farmacología , Isoenzimas/metabolismo , Isoflavonas/farmacología , Fosfolipasa C gamma , Conejos , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Fosfolipasas de Tipo C/metabolismoRESUMEN
BACKGROUND AND PURPOSE: Functional MR (fMR) imaging is based on changes in regional blood flow. The purpose of this study was to evaluate the role of fMR imaging for detection of a vascular compromised status in the occipital lobe in patients with ischemia in the visual cortex. METHODS: We performed fMR imaging in seven control subjects and seven patients with symptoms and signs of visual cortical transient ischemia and/or infarct. fMR imaging was performed using a gradient-echo sequence with the 2D fast low-angle shot technique. An axial slice including both visual cortices was selected, and stimulation of the visual cortex was performed using a red photostimulator. The number of activated pixels in each primary visual cortex area were counted and an asymmetry ratio [AR (%) = 100 x (R-L)/(R+L)/2] was calculated. Patients and control subjects underwent visual field examination, conventional MR imaging, and vascular imaging (MR angiography in all patients and control subjects, conventional catheter angiography in two patients). fMR imaging results were compared with the results of a visual field examination, conventional MR imaging, and vascular imaging. RESULTS: fMR imaging of the patients showed significant activation asymmetry (P <.05) compared with that of control subjects. Vascular abnormalities in the posterior circulation were found in all seven patients. By conventional MR imaging, five patients were found to have infarction in the occipital lobe and the remaining two patients showed no abnormality. In visual field examination, six of the seven patients showed homonymous hemi- or quadrantanopsia suggesting postchiasmic abnormalities, and the remaining patient had normal findings. fMR imaging showed decreased activity in the visual cortices corresponding to vascular abnormalities (seven of seven patients), permanent infarction (five of seven patients), or visual field defect (six of seven patients). Two patients with normal conventional MR imaging had vascular lesions in the posterior circulation, and fMR imaging showed decreased activity in the corresponding visual cortices. One patient with normal visual field examination had multifocal stenosis in the posterior cerebral artery without infarction, and fMR imaging showed decreased activity in the corresponding visual cortex. CONCLUSION: fMR imaging of the visual cortex may be a sensitive method for the detection of vascular-compromised status in the occipital lobe.
Asunto(s)
Infarto Cerebral/diagnóstico , Ataque Isquémico Transitorio/diagnóstico , Imagen por Resonancia Magnética , Corteza Visual/irrigación sanguínea , Adulto , Anciano , Infarto Cerebral/fisiopatología , Diagnóstico Diferencial , Dominancia Cerebral/fisiología , Femenino , Humanos , Ataque Isquémico Transitorio/fisiopatología , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Valores de Referencia , Flujo Sanguíneo Regional/fisiología , Corteza Visual/patologíaRESUMEN
PURPOSE: To compare the effectiveness, safety, and stability of laser epithelial keratomileusis (LASEK), a modified photorefractive keratectomy (PRK) technique, with those of conventional PRK for low to moderate myopia. SETTING: Department of Ophthalmology, Yonsei University School of Medicine, Seoul, Korea. METHODS: In this prospective study, 27 patients with a manifest refraction of -3.00 to -6.50 diopters were treated and followed for 3 months. In each case, PRK was performed in 1 eye and LASEK in the other eye. The first eye treated and the surgical method used in the first eye were randomized. Postoperative pain, epithelial healing time, uncorrected visual acuity (UCVA), manifest refraction, corneal haze, and surgical preference were examined in PRK- and LASEK-treated eyes. RESULTS: During the 3 month follow-up, there were no significant between-eye differences in epithelial healing time, UCVA, or refractive error. However, LASEK-treated eyes had lower postoperative pain scores (P =.047) and corneal haze scores (1 month; P =.02) than PRK-treated eyes. Seventeen patients (63%) preferred the LASEK procedure. CONCLUSIONS: Laser epithelial keratomileusis safely and effectively treated eyes with low to moderate myopia. It reduced the incidence of significant postoperative pain and corneal haze and may prevent the flap- and interface-related problems of laser in situ keratomileusis.
Asunto(s)
Córnea/cirugía , Queratomileusis por Láser In Situ , Miopía/cirugía , Queratectomía Fotorrefractiva , Adulto , Femenino , Estudios de Seguimiento , Humanos , Láseres de Excímeros , Masculino , Dolor Postoperatorio/prevención & control , Estudios Prospectivos , Refracción Ocular , Seguridad , Resultado del Tratamiento , Agudeza Visual , Cicatrización de HeridasRESUMEN
PURPOSE: Although transforming growth factor-betas (TGF-beta s) inhibit epithelial cell proliferation, these same substances stimulate cell proliferation of fibroblasts. In order to elucidate the mechanism of stimulatory activity of TGF-beta on fibroblast, the present study was performed to determine whether TGF-beta might be an indirect mitogen acting through induction of an endogenous growth factor(s) that then acts as the direct mitogen in an autocrine manner in corneal stromal fibroblasts (CSFs). METHODS: Cell proliferation was determined either by counting cell numbers or by analyzing the incorporation of [3H]-thymidine into DNA. The synthesis of TGF-beta, TGF-beta receptors, FGF-2 and p27 was analyzed by immunoprecipitation and immunoblotting. RESULTS: TGF-beta 1, TGF-beta 2, and TGF-beta 3 significantly stimulated cell proliferation of CSFs in a dose-dependent manner. The medium conditioned by CSFs and subsequently activated by acid-inhibited cell proliferation of corneal endothelial cells by 40%. When the acid-activated media conditioned by CSFs were immunoprecipitated with either combined anti-TGF-beta 1 and TGF-beta 2 antibodies or anti-TGF-beta 3 antibody, all three TGF-beta s, with an apparent molecular size of 25 kDa, were detected, whereas CSFs produced an 80-kDa latent form of TGF-beta 1. These cells can also express TGF-beta type II receptor and betaglycan. Interestingly, CSFs produced and secreted 18-kDa FGF-2, the synthesis of which is further stimulated by either TGF-beta 1 or TGF-beta 3, while both the neutralizing antibody to FGF-2 and the FGF-2 specific antisense oligonucleotide primers significantly inhibited the stimulatory activities of TGF-beta 1 in CSFs. The expression of p27, a negative regulator in cell cycle, was not altered by TGF-beta. CONCLUSIONS: These findings indicate that CSFs produce both TGF-beta s and FGF-2 and that FGF-2 appears to be a direct stimulator for TGF-beta-mediated cell proliferation in CSFs.
Asunto(s)
Proteínas de Ciclo Celular , Sustancia Propia/citología , Factor 2 de Crecimiento de Fibroblastos/biosíntesis , Factor de Crecimiento Transformador beta/farmacología , Proteínas Supresoras de Tumor , Animales , Recuento de Células , División Celular/efectos de los fármacos , Células Cultivadas , Sustancia Propia/efectos de los fármacos , Sustancia Propia/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Replicación del ADN , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Poliacrilamida , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Técnicas para Inmunoenzimas , Proteínas Asociadas a Microtúbulos/biosíntesis , Oligonucleótidos Antisentido/química , Conejos , Receptores de Factores de Crecimiento Transformadores beta/biosíntesis , Factor de Crecimiento Transformador beta/biosíntesis , Regulación hacia ArribaRESUMEN
PURPOSE: A prospective study was conducted to compare the effectiveness, safety, and stability of photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK) for correction of low to moderate myopia. METHODS: Forty-five patients with a manifest refraction (PRK, -4.54 +/- 0.80; LASIK, -4.82 +/- 1.10) from -1.50 to -6.00 diopters (D) were treated and followed-up for 6 months. In each case, 1 eye received PRK and the other LASIK. The first eye treated, and the surgical method used in the first eye, were randomized. Uncorrected and corrected visual acuity, manifest refraction, corneal haze, and topographic analysis of ablation decentration were examined. RESULTS: The uncorrected visual acuity was 20/20 or better in 35 PRK eyes (77.8%) and 28 LASIK eyes (62.2%) at 6 months (P =.107). At 6 months, 28 eyes (62.2%) that received PRK showed a spherical equivalent of within +/-0.5 D as compared with 24 eyes (53.4%) that received LASIK (P =.393). The amount of ablation decentration was 0.37 +/- 0.25 mm in PRK eyes and 0.49 +/- 0.38 mm in LASIK eyes at 3 months (P =.36). CONCLUSIONS: In our study, PRK and LASIK were found to be similarly effective and predictive of correction in low to moderate myopia. PRK has the advantage of less ablation decentration and is safer than LASIK, so we recommend PRK for eyes with low to moderate myopia.
Asunto(s)
Córnea/cirugía , Queratomileusis por Láser In Situ/métodos , Miopía/cirugía , Queratectomía Fotorrefractiva/métodos , Femenino , Estudios de Seguimiento , Humanos , Láseres de Excímeros , Masculino , Estudios Prospectivos , Seguridad , Resultado del Tratamiento , Agudeza VisualRESUMEN
BACKGROUND AND OBJECTIVE: To determine the prophylactic effect of 0.2% brimonidine in reducing the elevated intraocular pressure (IOP) in patients undergoing Nd:YAG laser posterior capsulotomy. PATIENTS AND METHODS: The 81 patients (81 eyes), who underwent Nd:YAG laser posterior capsulotomy, were allocated to two treatment groups. One drop of 0.2% brimonidine or vehicle was instilled 1 hour preoperatively and one drop immediately after capsulotomy. IOPs were measured preoperatively and 1, 2, 3, and 24 hours postoperatively. RESULTS: Intraocular pressure decreased from the baseline in the brimonidine group by the third postoperative hour (P<0.05), while the vehicle group exhibited an increase. Intraocular pressure elevations of 5 mm Hg or greater occurred in 7.3% (3/41) in the brimonidine group compared to 20.0% (8/40) in the vehicle group. IOP elevations of 10 mm Hg or greater occurred in 2.4% (1/41) in the brimonidine group compared to 7.5% (3/40) in the vehicle group. CONCLUSIONS: One drop of 0.2% brimonidine instilled 1 hour preoperatively and immediately after capsulotomy was found to be efficacious and safe in preventing IOP elevations that frequently follow Nd:YAG laser posterior capsulotomy.
Asunto(s)
Agonistas alfa-Adrenérgicos/uso terapéutico , Presión Intraocular/efectos de los fármacos , Terapia por Láser/efectos adversos , Cápsula del Cristalino/cirugía , Hipertensión Ocular/prevención & control , Quinoxalinas/uso terapéutico , Agonistas alfa-Adrenérgicos/administración & dosificación , Tartrato de Brimonidina , Extracción de Catarata , Método Doble Ciego , Femenino , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Hipertensión Ocular/etiología , Soluciones Oftálmicas , Estudios Prospectivos , Quinoxalinas/administración & dosificaciónRESUMEN
Retinal pigment epithelial (RPE) cells transdifferentiate in culture, a transition which is accompanied by a shift in biological activity. The present study investigates whether transforming growth factor (TGF)-beta has the same effects on morphologically transformed RPE cells that it has on primary RPE cells. It also evaluates the autocrine and paracrine activities of TGF-beta s synthesized by RPE cells as well as the anti-TGF-beta effect of mannose-6-phosphate (M-6-P). RPE cells were subcultured at the sixth passage to induce morphological change. The effect of second passaged RPE-conditioned medium (CM) on DNA synthesis was evaluated by the incorporation of 3H-thymidine in rabbit subconjunctival fibroblasts (SCFs) and primary RPE cells. The presence of TGF-beta in RPE-CM was determined using immunoblotting analysis. And the inhibitory effect of M-6-P on cell proliferation mediated by RPE-CM was also analyzed using 3H-thymidine incorporation into DNA. TGF-beta 1, TGF-beta 2, and TGF-beta 3 inhibited the proliferation of the primary cultures of RPE cells in a dose-dependent manner, but the spindle-shaped sixth passaged RPE cells were not inhibited by these growth factors. The medium conditioned by RPE cells stimulated the proliferation of SCFs and inhibited the proliferation of primary RPE cells, in a manner similar to TGF-beta. When this medium was precipitated with either anti-TGF-beta 1, anti-TGF-beta 2, or anti-TGF-beta 3 antibodies, all three TGF-beta s, with an apparent molecular size of 25 kDa, were detected. Mannose-6-phosphate significantly blocked the effect of RPE-CM on cell proliferation. These findings indicate that RPE cells produce biologically functional TGF-beta s and that M-6-P can block the inhibitory effect of RPE-CM on cell proliferation.
Asunto(s)
Epitelio Pigmentado Ocular/metabolismo , Factor de Crecimiento Transformador beta/biosíntesis , Animales , División Celular/efectos de los fármacos , Células Cultivadas , Conjuntiva/citología , Conjuntiva/efectos de los fármacos , Conjuntiva/metabolismo , Medios de Cultivo Condicionados/farmacología , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Immunoblotting , Manosafosfatos/farmacología , Epitelio Pigmentado Ocular/citología , Epitelio Pigmentado Ocular/efectos de los fármacos , Conejos , Porcinos , Factor de Crecimiento Transformador beta/antagonistas & inhibidoresRESUMEN
To investigate changes in the level of matrix metalloproteinase-2 (MMP-2) in the anterior chamber of rabbit with intraocular pressure (IOP) elevation. The IOP was elevated with scleral encircling in 12 rabbits. In the control group (4 rabbits), IOP was not changed after scleral encircling, and in group 1 (4 rabbits) and 2 (4 rabbits), IOP was elevated about 10 and 20 mmHg respectively after scleral encircling. At 2 days after scleral encircling, aqueous sampling was performed and levels of MMP-2 were checked by Western blots and gelatin zymograms. The greater the IOP elevation, the more MMP-2 expression in the anterior chamber by Western blots and gelatin zymograms. The increase in MMP-2 expression in response to IOP elevation may have important implications for the IOP feedback control mechanism.
Asunto(s)
Cámara Anterior/enzimología , Humor Acuoso/enzimología , Presión Intraocular , Metaloproteinasa 2 de la Matriz/metabolismo , Hipertensión Ocular/enzimología , Animales , Biomarcadores , Western Blotting , Hipertensión Ocular/etiología , Conejos , Esclerótica/cirugía , Tapones Quirúrgicos de Gaza/efectos adversosRESUMEN
PURPOSE: Tube-corneal touch occurring after Ahmed glaucoma valve (AGV) implantation is conventionally treated by tube cutting or tube transposition from the original pathway. However, in some cases, tube cutting is insufficient, and rearranging the pathway of the tube through a new sclera tunnel, ciliary sulcus, or pars plana is not feasible, as the conjunctiva and sclera covering the tube are difficult to be redissected. So, we propose a novel technique that repositions malpositioned AGV tube using scleral fixation and its successful applications in two patients with tube-corneal touch. METHODS: (A) A scleral flap is made at the point for scleral fixation. (B) The anterior chamber is maintained using an anterior chamber maintainer. The incision is made immediately above the tube entering the anterior chamber and the tube end is flipped out using a Sinskey. (C) A double-armed 10/0 prolene straight needle is penetrated through the tube end. The leading needle enters the anterior chamber through the previously made incision and is pulled through the scleral flap. (D) The tube tip and the second needle of the double-armed 10/0 prolene straight needle also enter the anterior chamber through the previously made incision and the second needle is pulled through the scleral flap. The tube end is extended to be parallel to the cornea surface. RESULTS: Patients maintained good tube positioning without any serious complications during average of 15 months of follow-up after operation. CONCLUSION: We believe that our method is a simple and minimally invasive surgical method for treating AGV tube touching of the corneal endothelium. However, considering the limited number of cases studied and the short follow-up period, a larger group with a longer follow-up period is necessary.
Asunto(s)
Edema Corneal/cirugía , Implantes de Drenaje de Glaucoma/efectos adversos , Glaucoma de Ángulo Cerrado/cirugía , Implantación de Prótesis/métodos , Esclerótica/cirugía , Edema Corneal/etiología , Femenino , Humanos , Presión Intraocular , Persona de Mediana Edad , Polipropilenos , Reoperación , Colgajos Quirúrgicos , Técnicas de Sutura , Suturas , Tonometría OcularRESUMEN
Agmatine, an endogenous polyamine and putative neuromodulator, is known to have neuroprotective effects on various neurons in the central nervous system. We determined whether or not topically administered agmatine could reduce ischemic retinal injury. Transient ocular ischemia was achieved by intraluminal occlusion of the middle cerebral artery of ddY mice (30-35 g) for 2 h, which is known to also induce occlusion of the ophthalmic artery. In the agmatine group (N = 6), a 1.0 mM agmatine-containing ophthalmic solution was administered four times daily for 2 weeks before occlusion. In the control group (N = 6), a 0.1% hyaluronic acid ophthalmic solution was instilled at the same times. At 22 h after reperfusion, the eyeballs were enucleated and the retinal sections were stained by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Transient ocular ischemia induced apoptosis of retinal cells in the entire retinal layer, and topically administered agmatine can significantly reduce this ischemic retinal injury. The proportion of apoptotic cells was definitely decreased (P < 0.001; Kruskal-Wallis test). Overall, we determined that topical agmatine application effectively decreases retinal damage in an in vivo ocular ischemic injury model. This implies that agmatine is a good candidate as a direct neuroprotective agent for eyes with ocular ischemic diseases.
Asunto(s)
Agmatina/administración & dosificación , Arteriopatías Oclusivas/complicaciones , Isquemia/tratamiento farmacológico , Fármacos Neuroprotectores/administración & dosificación , Arteria Oftálmica , Enfermedades de la Retina/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Isquemia/etiología , Masculino , Ratones , Enfermedades de la Retina/etiologíaRESUMEN
BACKGROUND/AIMS: Although studies using optical coherence tomography (OCT) reported that the retinal nerve fibre layer (RNFL) thickness of myopic eyes was thinner than those of normal controls, it was unclear if this finding indicated the difference in actual structural thickness or that created by sources affecting accuracy of OCT measurement. This study's aim was to evaluate the effect of refraction power on the measurement of the RNFL thickness using spectral-domain OCT. METHODS: OCT scans to measure RNFL thickness were repeated in 15 cycloplegic eyes of 15 participants, while different refraction powers were induced by wearing soft contact lenses of eight different dioptres (-6 to +8). RESULTS: Measured RNFL thicknesses decreased significantly with soft contact lenses of higher plus dioptres and increased with those of more minus dioptres. This finding was consistent with or without controlling factors including the signal strength and test-retest variability of the machine. Measurement of peripapillary RNFL thicknesses was not varied between scans performed with and without plano contact lenses. CONCLUSIONS: In spectral-domain OCT, RNFL thickness was underestimated in eyes with increasing negative refraction power and overestimated with increasing positive refraction power.
Asunto(s)
Errores Diagnósticos , Miopía/patología , Fibras Nerviosas/patología , Refracción Ocular , Células Ganglionares de la Retina/patología , Tomografía de Coherencia Óptica/métodos , Adulto , Femenino , Humanos , Masculino , Miopía/fisiopatología , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
Agmatine has neuroprotective effects on retinal ganglion cells (RGCs) as well as cortical and spinal neurons. It protects RGCs from oxidative stress even when it is not present at the time of injury. As agmatine has high affinity for various cellular receptors, we assessed protective mechanisms of agmatine using transformed RGCs (RGC-5 cell line). Differentiated RGC-5 cells were pretreated with 100 muM agmatine and consecutively exposed to 1.0 mM hydrogen peroxide (H2O2). Cell viability was determined by measuring lactate dehydrogenase (LDH), and the effects of selective alpha 2-adrenergic receptor antagonist yohimbine (0-500 nM) and N-methyl-D-aspartic acid (NMDA) receptor agonist NMDA (0-100 microM) were evaluated. Agmatine's protective effect was compared to a selective NMDA receptor antagonist MK-801. After a 16-h exposure to H2O2, the LDH assay showed cell loss greater than 50%, which was reduced to about 30% when agmatine was pretreated before injury. Yohimbine almost completely inhibited agmatine's protective effect, but NMDA did not. In addition, MK-801 (0-100 microM) did not significantly attenuate the H2O2-induced cytotoxicity. Our results suggest that neuroprotective effects of agmatine on RGCs under oxidative stress may be mainly attributed to the alpha 2-adrenergic receptor signaling pathway.
Asunto(s)
Agmatina/farmacología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Células Ganglionares de la Retina/efectos de los fármacos , Antagonistas de Receptores Adrenérgicos alfa 2/farmacología , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patologíaRESUMEN
PURPOSE: We described the techniques and results of phacoemulsification using iris hook and scleral fixation of intraocular lens (IOL) in patients with secondary glaucoma associated with lens subluxation. METHODS: Eight eyes of seven patients with secondary glaucoma associated with lens dislocation, who had undergone the surgery, were retrospectively reviewed. RESULTS: At a mean of 23.5 months+/-13.6 (SD) after the surgery, the mean best-corrected visual acuity improved from 0.24+/-0.21 to 0.83+/-0.3, and mean intraocular pressure (IOP) was changed from 38.4+/-11.4 to 15.5+/-1.8 mmHg at the final examination. There were no vitreoretinal complications except cystoid macular oedema in one eye. CONCLUSION: The technique appears to be safe and effective in terms of visual rehabilitation and controlling IOP in patients with secondary glaucoma associated with lens subluxation.
Asunto(s)
Glaucoma/complicaciones , Iris/cirugía , Subluxación del Cristalino/cirugía , Lentes Intraoculares/efectos adversos , Facoemulsificación/métodos , Esclerótica/cirugía , Adulto , Anciano , Femenino , Glaucoma/cirugía , Humanos , Presión Intraocular/fisiología , Subluxación del Cristalino/complicaciones , Masculino , Persona de Mediana Edad , Facoemulsificación/instrumentación , Estudios Retrospectivos , Instrumentos Quirúrgicos , Agudeza Visual/fisiologíaRESUMEN
Agmatine, an endogenous polyamine and putative neuromodulator, is known to have neuroprotective effects on various neurons in the central nervous system. We determined whether or not topically administered agmatine could reduce ischemic retinal injury. Transient ocular ischemia was achieved by intraluminal occlusion of the middle cerebral artery of ddY mice (30-35 g) for 2 h, which is known to also induce occlusion of the ophthalmic artery. In the agmatine group (N = 6), a 1.0 mM agmatine-containing ophthalmic solution was administered four times daily for 2 weeks before occlusion. In the control group (N = 6), a 0.1 percent hyaluronic acid ophthalmic solution was instilled at the same times. At 22 h after reperfusion, the eyeballs were enucleated and the retinal sections were stained by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Transient ocular ischemia induced apoptosis of retinal cells in the entire retinal layer, and topically administered agmatine can significantly reduce this ischemic retinal injury. The proportion of apoptotic cells was definitely decreased (P < 0.001; Kruskal-Wallis test). Overall, we determined that topical agmatine application effectively decreases retinal damage in an in vivo ocular ischemic injury model. This implies that agmatine is a good candidate as a direct neuroprotective agent for eyes with ocular ischemic diseases.
Asunto(s)
Animales , Masculino , Ratones , Agmatina/administración & dosificación , Arteriopatías Oclusivas/complicaciones , Isquemia/tratamiento farmacológico , Fármacos Neuroprotectores/administración & dosificación , Arteria Oftálmica , Enfermedades de la Retina/tratamiento farmacológico , Modelos Animales de Enfermedad , Isquemia/etiología , Enfermedades de la Retina/etiologíaRESUMEN
Agmatine has neuroprotective effects on retinal ganglion cells (RGCs) as well as cortical and spinal neurons. It protects RGCs from oxidative stress even when it is not present at the time of injury. As agmatine has high affinity for various cellular receptors, we assessed protective mechanisms of agmatine using transformed RGCs (RGC-5 cell line). Differentiated RGC-5 cells were pretreated with 100 ìM agmatine and consecutively exposed to 1.0 mM hydrogen peroxide (H2O2). Cell viability was determined by measuring lactate dehydrogenase (LDH), and the effects of selective alpha 2-adrenergic receptor antagonist yohimbine (0-500 nM) and N-methyl-D-aspartic acid (NMDA) receptor agonist NMDA (0-100 µM) were evaluated. Agmatines protective effect was compared to a selective NMDA receptor antagonist MK-801. After a 16-h exposure to H2O2, the LDH assay showed cell loss greater than 50 percent, which was reduced to about 30 percent when agmatine was pretreated before injury. Yohimbine almost completely inhibited agmatines protective effect, but NMDA did not. In addition, MK-801 (0-100 µM) did not significantly attenuate the H2O2-induced cytotoxicity. Our results suggest that neuroprotective effects of agmatine on RGCs under oxidative stress may be mainly attributed to the alpha 2-adrenergic receptor signaling pathway.
Asunto(s)
Animales , Ratas , Agmatina/farmacología , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Células Ganglionares de la Retina/efectos de los fármacos , /farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Ratas Sprague-Dawley , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patologíaRESUMEN
Fifty-two eyes of 26 healthy volunteers were recruited for evaluating the effects of 0.005% latanoprost on optic nerve head (ONH) and peripapillary retinal blood flow. In a randomized double-blind design, one eye received one drop of 0.005% latanoprost and its fellow eye received one drop of a placebo eyedrop. Intraocular pressure (IOP), ONH and peripapillary retinal blood flow were measured with Heidelberg retinal flowmetry (HRF) before, 2 and 24 h after administration of eyedrops. IOP was decreased significantly in latanoprost-treated eyes at 2 and 24 h after administration (p < 0.05). In the volume, flow or velocity of ONH and peripapillary retina, there were no significant changes from the baseline values at 2 and 24 h after latanoprost administration in either latanoprost-treated eyes or their fellow eyes (p > 0.05). No significant differences were found in the measured quantities between latanoprost-treated eyes and their fellow eyes at each time point (p > 0.05). This result may suggest that 0.005% latanoprost in healthy subjects does not have any adverse effect on ONH and peripapillary retinal blood flow.
Asunto(s)
Disco Óptico/irrigación sanguínea , Disco Óptico/efectos de los fármacos , Prostaglandinas F Sintéticas/farmacología , Vasos Retinianos/efectos de los fármacos , Adulto , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Método Doble Ciego , Femenino , Humanos , Presión Intraocular/efectos de los fármacos , Flujometría por Láser-Doppler , Latanoprost , Masculino , Soluciones Oftálmicas/farmacología , Valores de Referencia , Flujo Sanguíneo Regional/efectos de los fármacos , Reproducibilidad de los Resultados , Vasos Retinianos/fisiologíaRESUMEN
Retinal pigment epithelium (RPE) cells of the proliferative vitreoretinopathy (PVR) membrane take on the shape of fibroblasts and participate in fibrosis, thus deviating from the character of epithelial cells. This study was undertaken to evaluate RPE cell transdifferentiation in vitro. During the culture of porcine RPE cells, primary and 10th-passaged RPE cells were investigated for cell growth in response to transforming growth factor (TGF) beta(2), change of phenotype and amount in collagen synthesis as well as expression of alpha-smooth-muscle actin (alpha-SMA). TGF-beta(2) inhibited the proliferation of the primary cultures of RPE cells in a dose-dependent manner, while the spindle-shaped 10th-passaged RPE cells were not inhibited by TGF-beta(2). The 10th-subcultured cells did not show much difference in the quality of collagen synthesis, other than type VIII collagen which was not produced. Collagen synthesis was dose-dependently stimulated by TGF-beta(2). The stimulation by TGF-beta(2) in the 10th-passaged RPE cells was much greater than in primary RPE cells. The 10th-subcultured RPE cells produced substantial alpha-SMA compared to alpha-SMA production by primary RPE cells. These results were also observed by confocal laser microscopy. These findings indicated that RPE metaplasia resulting in a change of biological cell behavior might be a necessary predisposing step in the development of PVR.
Asunto(s)
Epitelio Pigmentado Ocular/patología , Actinas/biosíntesis , Animales , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Células Cultivadas , Colágeno/biosíntesis , Relación Dosis-Respuesta a Droga , Metaplasia , Fenotipo , Epitelio Pigmentado Ocular/efectos de los fármacos , Epitelio Pigmentado Ocular/metabolismo , Porcinos , Factor de Crecimiento Transformador beta/farmacología , Factor de Crecimiento Transformador beta2 , Vitreorretinopatía Proliferativa/patologíaRESUMEN
Forty-one healthy volunteers were recruited for a study to compare the intraocular pressure (IOP)-lowering efficacy and side effects of 2% dorzolamide and 1% brinzolamide. In a randomized double-blind design, one eye received one drop of 2% dorzolamide and the other eye received one drop of 1% brinzolamide. The IOP and side effects were evaluated by Goldmann applanation tonometry and slit lamp biomicroscopy before administration, and 3, 7 and 14 days after the initial administration of eyedrops. The IOP decreased significantly from baseline for both drugs (p < 0.05). However, there were no statistically significant differences between 2% dorzolamide and 1% brinzolamide either before or after eyedrop administration (p > 0.05). The most frequent side effect was ocular pain in the case of 2% dorzolamide and blurred vision in 1% brinzolamide. The results suggested that 2% dorzolamide and 1% brinzolamide have similar IOP-lowering efficacies with different side effects
Asunto(s)
Inhibidores de Anhidrasa Carbónica/farmacología , Presión Intraocular/efectos de los fármacos , Sulfonamidas/farmacología , Tiazinas/farmacología , Tiofenos/farmacología , Adulto , Inhibidores de Anhidrasa Carbónica/efectos adversos , Método Doble Ciego , Femenino , Humanos , Masculino , Soluciones Oftálmicas , Seguridad , Sulfonamidas/efectos adversos , Tiazinas/efectos adversos , Tiofenos/efectos adversos , Tonometría OcularRESUMEN
Agmatine, 2-(4-aminobutyl)guanidine, has been reported to have neuroprotective effects against various neuronal damages. In this study it was investigated whether agmatine pretreatment rescues the retinal ganglion cells from oxidative injury in vitro. Alter differentiation of transformed rat retinal ganglion cells (RGC-5 cell line) with staurosporine, agmatine (0.0 to 100.0 microM) pretreatment was performed for 2 hours. Subsequently, they were exposed to hydrogen peroxide (0.0 to 2.5 mM) as an oxidative stress. Cell viability was monitored for up to 48 hours with the lactate dehydrogenase (LDH) assay and apoptosis was examined by the Terminal deoxynucleotide transferase-mediated terminal uridine deoxynucleotidyl transferase nick end-labeling (TUNEL) method. As a result, differentiated RGC-5 cells were found to have decreased viability after addition of hydrogen peroxide in a dose-dependent manner. This hydrogen peroxide induced cytotoxicity caused apoptosis characterized by DNA fragmentation. Agmatine pretreatment not only increased cell viability but also attenuated DNA fragmentation. In conclusion, agmatine pretreatment demonstrated neuroprotective effects against oxidative stress induced by hydrogen peroxide in differentiated RGC-5 cells in vitro. This suggests a novel therapeutic strategy rescuing retinal ganglion cells from death caused by oxidative injury.
Asunto(s)
Animales , Ratas , Agmatina/farmacología , Apoptosis , Células Ganglionares de la Retina , Células Ganglionares de la Retina/metabolismo , Estrés Oxidativo , Inhibidores Enzimáticos/farmacología , Fármacos Neuroprotectores/farmacología , Línea Celular , Diferenciación Celular , Estaurosporina/farmacologíaRESUMEN
The effect of hypoxia on the release of tumor necrosis factor-alpha (TNF-alpha) in transformed rat retinal ganglion cells (RGCs) and the effect of agmatine on the hypoxia-induced production of TNF-alpha in RGCs were evaluated. RGCs were cultured under hypoxic conditions with 5% oxygen, with or without 100 microM agmatine. The expression levels of TNF-alpha and its receptor-1 (TNF-R1) were investigated by Western blot analysis. After 6 hours of hypoxia, we noted an increase in TNF-alpha production in RGCs. Agmatine significantly reduced TNF-alpha level after 12 hours of hypoxic treatment. The expression of TNF-R1 was not affected by the hypoxia or agmatine treatment. Our results show that agmatine inhibits the TNF-alpha production of RGCs in hypoxic condition. These results demonstrate a possible neuroprotective mechanism for agmatine against hypoxic damage in RGCs.