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Biomedical subjects

T Moritera

Publications and source records attributed to T Moritera.

15 recordsLinked to original sources

[The relation of retinal vascular occlusion and carotid artery stenosis].

We evaluated carotid ulceration and stenosis in 16 patients with central retinal artery occlusion (CRAO), 13 patients with branch retinal artery occlusion (BRAO), and 27 patients with central retinal vein occlusion (CRVO). One of three kinds of angiography was selected according to the patient's condition. These included conventional cerebral angiography, intravenous digital subtraction angiography (IVDSA), and magnetic resonance angiography (MRA). Carotid artery stenosis (50% or greater) was noted in 37.5% (6/16) of the patients with CRAO and in 23.1% (3/13) of the patients with BRAO. Only one of 27 patients with CRVO had a contralateral 50% carotid artery stenosis. In order to detect an underlying systemic disease in evaluating patients with retinal artery occlusion, examination of the carotid vessels is essential. It may also be helpful to estimate the risk of cerebral stroke for patients with retinal stroke.

Adult↗

Experimental retinal tolerance to very low viscosity silicone oil (100 cs) as a vitreous substitute compared to higher viscosity silicone oil (5000 cs).

We evaluated the toxicity of very low viscosity (100 centistokes) and higher viscosity silicone oil (5000 centistokes) in rabbit eyes as a short-to-long-term postoperative vitreous substitute (6 weeks to 5 months). Emulsification of 100-cs and 5000-cs silicone oil did not occur in eyes which were followed for as long as 5 months. No toxic effects to retinal cells were detected by light or electron microscopy. Because no toxic effects were seen with 100-cs silicone oil, it can be used in an outpatient setting as a short-term postoperative tamponading agent. Electroretinographic responses of silicone-injected eyes were normal.

Animals↗

Scleral plug of biodegradable polymers for controlled drug release in the vitreous.

We designed a new device, a scleral plug, that releases drugs into the vitreous after being implanted and fixed at the pars plana. Use of the plug for provision of doxorubicin hydrochloride was evaluated in rabbits. The scleral plug (8.5 mg) was made of poly(lactic-glycolic acid) (molecular weight, 40,000 daltons) containing 1% doxorubicin. Vitreous concentrations of doxorubicin were measured after the implantation. In vitro studies showed that the plug released 26% of the drug during 4 weeks. In vivo studies demonstrated that the concentration in the vitreous humor was maintained at a therapeutic range for longer than 4 weeks. No substantial toxic reactions were observed by electroretinographic and histopathologic evaluations. Our findings suggested that a scleral plug made of biodegradable polymers is a promising device for a controlled drug-release system in the vitreous.

Animals↗

Contact diode laser: high power application through fiberoptic cutting tips.

Diode laser energy has been applied through a fiberoptic probe using a power setting of 2.5 watts (W) in the continuous mode. In this study we employed high-power diode laser energy (4 to 12 W, continuous wave) to incise ocular tissue through a fiberoptic probe using 100 microns and 300 microns tips. The retina was photocoagulated with a 300 microns orb tip. No bleeding occurred at the incision sites. Histologic evaluation revealed coagulation into the healthy tissue ranging from 10 to 50 microns.

Animals↗

Feasibility of drug targeting to the retinal pigment epithelium with biodegradable microspheres.

There are several systems of delivering drugs to cells with phagocytic activity. We studied the possibility of targeting drugs to retinal pigment epithelial (RPE) cells with the use of surface-modified microspheres. A fluorescent dye, 1,4-bis[2-(5-phenyloxazolyl)]-benzene (POPOP), was incorporated into microspheres of poly(lactic acid) for use as a marker to evaluate drug delivery. Phagocytosis of the microspheres, with or without gelatin precoating, was carried out at 37 degrees C and 4 degrees C. The cell-incorporated fluorescence of POPOP was measured, and scanning electron microscopy was used to confirm phagocytosis. At 4 degrees C, no uptake of POPOP was noted; however at 37 degrees C, cell-associated fluorescence was observed to increase for up to 24 hr. In comparison with bare microspheres, gelatin precoating significantly enhanced phagocytosis (P < 0.001) at the same incubation times. These results suggested that drug delivery to RPE cells may be feasible by means of surface-modified polymer microspheres.

Animals↗

In vitro phagocytosis of polylactide microspheres by retinal pigment epithelial cells and intracellular drug release.

We investigated phagocytosis of biodegradable microspheres containing a drug by retinal pigment epithelial (RPE) cells and drug release within the cells to evaluate the potential usefulness of microspheres for intracellular drug delivery. The biodegradable polymers used were L-lactic acid, and DL-lactic acid with different molecular weights or the copolymers of different monomer compositions. The microspheres containing a non-bioactive fluorescent dye (rhodamine 6GX) as a model drug, were prepared by a solvent evaporation method. The in vitro release of the dye from the microspheres was examined. Phagocytosis of the microspheres by RPE cells was conducted to evaluate the extent of phagocytosis by phase-contrast microscopy and transmission electron microscopy. The RPE cells ingesting the microspheres at different stages were examined by fluorescent microscopy to estimate the intracellular release of the dye. The dye was released with time from every microsphere and the release was controlled by changing the type of polymers constituting microspheres. The microspheres containing the dye were phagocytosed by RPE cells and the dye was released intracellularly with time. The present study indicates that the drug incorporated in the microspheres was delivered into RPE cells by way of phagocytosis and released within the cells. It is concluded that this microsphere system is a promising delivery form capable of drug targeting to RPE cells.

Animals↗

Breakdown of the blood-retinal barrier after radiofrequency-induced ocular hyperthermia.

To study the possible application of hyperthermia in the treatment of proliferative vitreoretinopathy (PVR), we induced hyperthermia in 15 normal rabbit eyes by a radiofrequency capacitive heating device. The retinal surface of each eye was warmed to a presumed temperature of 41 or 43 degrees C for 30 min. The thermal effect on the blood-retinal barrier (BRB) was evaluated before and 2 h after the hyperthermic regimen by means of vitreous fluorophotometry. Heat treatment to 43 degrees C at the retinal surface for 30 min increased the fluorescein leakage compared with the 41 degrees C treatment. This finding suggests that retinal hyperthermia at 43 degrees C for 30 min may cause breakdown of the BRB.

Animals↗

Tissue reactions induced by modified poly(vinyl alcohol) hydrogels in rabbit cornea.

The purpose of this study was to compare the tissue reactions induced by modified poly(vinyl alcohol) (PVA) hydrogels with other materials implanted in the rabbit cornea. PVA hydrogels with and without covalently bonded collagen were compared to ethylene-vinyl alcohol copolymer, and polysulfone discs. These materials were implanted in the rabbit corneal stroma. The resultant tissue reactions were histologically and clinically studied. The PVA hydrogels had high flux rates of glucose and L-lactic acid in vitro. Covalent immobilization of collagen onto their surface was found to render them more biocompatible. However, excessive ulceration and vascularization of the cornea still occurred in vivo, possibly because of extremely little blinking of the rabbits, which might cause desiccation of the cornea.

Animals↗

Mass cultivation of human retinal pigment epithelial cells with microcarrier.

Microcarrier cell culture permits mass cultivation of anchorage-dependent cells. In this study, mass cultivation of human retinal pigment epithelial (RPE) cells was studied using Cytodex 3 (Pharmacia) as a microcarrier. Human RPE cells were established from aborted fetuses and cultured in Dulbecco's modified Eagle's Medium (DMEM). After the 3rd-5th passages, RPE cells were suspended in 50 ml of DMEM in a spinner flask at a density of 2 x 10(5)/ml, and Cytodex 3 was added to the spinner flask at a bead density of 10 mg/ml. Cultures were maintained at 20-50 rpm (final speed) on a magnetic stirrer, and DMEM was added up to 100 ml. Fifty milliliters of DMEM were decanted and replaced with fresh DMEM every 2 days. After 1 week, a cell density of 10(6)/ml DMEM was obtained. Phase contrast microscopy showed bridging formation between microcarriers, which suggests tight cell adhesion. Microcarrier cell culture has a variety of advantages which include greater cell production, use of less medium and less risk of contamination compared to the conventional monolayer culture technique, and it also allows passaging without using proteases. Using this culture system, greater possibilities for wider application of new cell cultures can be expected.

Cell Count↗

Biodegradable microspheres containing adriamycin in the treatment of proliferative vitreoretinopathy.

The use of biodegradable polymer microspheres containing adriamycin for the treatment of proliferative vitreoretinopathy (PVR) in an experimental rabbit model was investigated. A single injection of microspheres containing 10 micrograms of adriamycin effectively decreased traction retinal detachment to 10% (n = 10), whereas 50% of eyes injected with blank microspheres (n = 10) developed retinal detachment (P < 0.05). A single injection of microspheres, containing 3 micrograms of adriamycin, did not suppress retinal detachment. Electroretinographic and histologic studies confirmed that the 10 micrograms injection of adriamycin in microspheres was not toxic to the retina, although the injection of the same amount of free adriamycin caused retinal necrosis and detachment. Thus, microspheres containing adriamycin hold promise as a new treatment modality for PVR.

Animals↗

Injectable microspheres with controlled drug release for glaucoma filtering surgery.

The authors evaluated the effects of biodegradable poly (lactic acid) microspheres that provided the controlled release of the antimetabolic agent adriamycin (ADR) to prevent post surgical fibrosis after glaucoma filtering surgery. Fifty six eyes of 28 rabbits underwent posterior lip sclerotomy and received a 0.2 ml subconjunctival injection that contained microspheres 90 degrees from the filtering site immediately after surgery. Microspheres containing ADR (100 or 200 micrograms) were randomly administered to one eye. The fellow eyes served as controls and received microspheres without the drug. Intraocular pressure in the eyes treated with the microspheres that contained the drug was significantly lower than that in the control eyes from days 7-12 in the 100 micrograms group and from days 6-16 in the 200 micrograms group (P < .05). Eyes that received ADR had a significantly longer patent filtering bleb compared with the control eyes (P < .05). No corneal complications were observed in the eyes treated with 100 micrograms of ADR and the control eyes. Peripheral corneal opacities (25%) and epithelial erosion (17%) were observed in the eyes that received the 200 micrograms dose, but the cornea returned to normal after 4 wk. These results suggest that controlled-drug-release microspheres with an antimetabolic agent may be promising for preventing fibrosis after surgery.

Animals↗

Collagen-immobilized hydrogel as a material for lamellar keratoplasty.

A transparent poly(vinyl alcohol) hydrogel disc covalently immobilized with Type I collagen, fibronectin, and an adhesive oligopeptide and preseeded with corneal epithelial cells was implanted in the rabbit cornea using a technique of lamellar keratoplasty, and the tissue response was studied by light and electron microscopy. Covalent immobilization of type I collagen on the surface of hydrogel was found to support growth and adhesion of the corneal epithelium in vitro. The in vivo experiment showed that cell seeding could prevent infection of the hydrogel. However, the implanted disc was rejected from the host cornea by epithelial downgrowth and the exchange between the seeded cells and host corneal epithelia was not observed until 14 days after surgery. The rejection might have occurred because of unsatisfactory fixation of the hydrogel to the host cornea.

Animals↗

Microspheres of biodegradable polymers as a drug-delivery system in the vitreous.

Microspheres of biodegradable polymers were evaluated as a potential controlled-release drug-delivery system in the vitreous. The microspheres were prepared with polymers of poly(lactic acid) or copolymers of glycolic acid and lactic acid. The release of 5-fluorouracil (5-FU) from the microspheres was studied in vitro. Poly(lactic acid) microspheres released 70-85% of total 5-FU over 7 days. Microspheres of polymers with a smaller molecular weight released the drug more rapidly. Copolymer microspheres released 98% of 5-FU over 2 days. The rate of drug release was controllable by changing the molecular weight of the polymers or using a matrix of copolymer. The intravitreal kinetics of the microspheres were studied in ten rabbits in vivo. A suspension of microspheres was injected into the vitreous cavity of five normal eyes and five vitrectomized eyes. By 48 +/- 5.2 days after injection, the microspheres disappeared from the vitreous cavity in the five normal eyes. Clearance from the vitreous cavity was accelerated in the five rabbits that underwent vitrectomy (14 +/- 2.4 days; P less than 0.001). No difference was found in the b waves of electroretinograms before and after injection of the microspheres. The histologic study showed no abnormal findings as a result of the injection. These results suggested that microspheres of biodegradable polymers may be a potential delivery system for the controlled release of drugs in the vitreous.

Animals↗

[Intravitreal drug delivery by microspheres of biodegradable polymers].

We evaluated the efficacy of microspheres of biodegradable polymers as a slow releasing drug delivery system in the vitreous body. Microspheres containing 5-FU were prepared with polymers of poly-(lactic acid) or copolymers of glycolic acid and lactic acid. The release of the drug was studied in vitro. Poly-(lactic acid) microspheres released 5-FU for 7 days. The intravitreal kinetics of the microspheres was studied in rabbits in vivo. The microspheres disappeared from the vitreous cavity of normal eyes by 48 +/- 5 days after injection. Disappearance was accelerated from the vitreous cavity of vitrectomized rabbits (14 +/- 2 days, p less than 10(-6)). No abnormality was found on electroretinographic or histological examinations after microspheres injection. These results suggested that microspheres of biodegradable polymers could be useful as a potential drug delivery system for sustained drug release in the vitreous body.

Animals↗