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Biomedical subjects

M O Tso

Publications and source records attributed to M O Tso.

At least 73 records · Page 4Linked to original sources
PubMed1992

An immunohistochemical study of gelsolin immunoreactivity in corneal amyloidosis.

A variant of the actin-modulating protein gelsolin has recently been identified as a component of the amyloid deposits in familial amyloidosis, Finnish type (Meretoja's syndrome), and has been demonstrated immunohistochemically in amyloid deposits in the cornea, and in the skin, kidney, heart, thyroid gland, salivary gland, and rectum of patients with this disease. With the use of immunohistochemistry involving an antibody against gelsolin, we examined a corneal specimen from a patient with Meretoja's syndrome and 14 corneal specimens with lattice dystrophy type I, atypical lattice dystrophy, polymorphic amyloid degeneration, primary familial amyloidosis, or secondary corneal amyloidosis. Our results showed the presence of a gelsolin-related protein either within or around corneal amyloid deposits in nine of the 15 specimens and markedly increased anti-gelsolin immunoreactivity of the corneal keratocytes in 13 of the 15 diseased corneas. These data indicated that the accumulation of gelsolin may be seen in various forms of amyloidosis and may not be confined to Meretoja's syndrome.

Adult↗
PubMed1992

Effects of intracameral injection of chondroitinase ABC in vivo.

A glycosaminoglycan-degrading enzyme, chondroitinase ABC, was introduced into the anterior chamber of three cynomolgus monkeys. Following the injection, the intraocular pressure decreased in the experimental eyes. Depending on the monkey, the intraocular pressure was lowered for 5, 7, or 14 days before it returned to the normal level. Repeated injections produced a similar response. Structurally, the intertrabecular spaces appeared widened, and marked ballooning of the juxtacanalicular tissue was observed. The outer trabecular beams and the inner wall of Schlemm's canal were greatly disorganized. Considerable loss of the juxtacanalicular tissue was noted even 2 months after the enzyme was injected into the anterior chamber. These observations suggest that chondroitinase ABC digested the trabecular glycosaminoglycans, triggering intraocular pressure reduction and causing disorganization of the extracellular matrices of the disorganized trabecular beams, especially in areas near Schlemm's canal.

Animals↗
PubMed1992

Methylprednisolone ameliorates retinal photic injury in rats.

Since lipid peroxidation induced by oxygen free radicals is believed to play an important role in retinal photic injury and high doses of certain steroids have been demonstrated to inhibit lipid peroxidation, we evaluated the effect of high-dose methylprednisolone sodium succinate on retinal injury inflicted by green light (490 to 580 nm, 160 to 180 foot-candles [1721.6 to 1936.8 lux]) for 24 hours in 36 rats. Animals received either intraperitoneal injections of the drug (80 mg/kg twice daily) or saline as a control, twice daily for 2 days, commencing with light exposure. The retinal photic injury was assessed 6 hours, 6 days, and 14 days after light exposure by light and electron microscopy, morphometric study of outer nuclear layer thickness and count of subretinal macrophages, and spectrophotometric measurement of rhodopsin. A beneficial effect of high-dose methylprednisolone was observed in retinal photic injury.

Animals↗
PubMed1992

Protective effects of flunarizine on ischemic injury in the rat retina.

Intracellular calcium overload has been implicated to be a major factor in triggering cell death after ischemic neuronal injury. We investigated the effects of flunarizine hydrochloride, a calcium-overload blocker, on pressure-induced retinal ischemia in a rat model. Retinal ischemia was induced in intraocular pressure to 110 mm Hg for 45 minutes. Two regimens of treatment with flunarizine were examined: (1) prophylactic treatment, in which flunarizine was administered before ischemia and in the early phase of reperfusion; and (2) postischemic treatment, in which flunarizine was administered only in the early phase of reperfusion. Injury was evaluated morphologically and morphometrically by measuring the thickness of the inner retinal layers on plastic-embedded retinal sections and by counting the retinal ganglion cells on retinal flat preparations. By morphologic and morphometric criteria, a significant but partial protection of the inner retinal layers was noted in the groups given either regimen. This protective effect of flunarizine suggests that elevated intracellular calcium concentration may play an important role in ischemic retinal injury.

Animals↗
PubMed1992

Dexamethasone ameliorates retinal photic injury in albino rats.

The effect of dexamethasone in two regimens on retinal photic injury was studied in Lewis albino rats that were exposed to 24 hr of continuous green fluorescent light. Under regimen 1, dexamethasone was given at a daily dosage of 1 mg kg-1 for 8 days, starting 6 days before light exposure. Under regimen 2, dexamethasone was given at the same daily dosage for 3 days, started 1 day before light exposure. Pathologic study of the light-exposed retina, morphometric evaluation of the photoreceptor cell loss, cell counts of the macrophages in the subretinal space, and measurements of rhodopsin levels were undertaken in the dexamethasone-treated and control retinas at various times. The administration of dexamethasone in both regimens did not produce pathologic changes in the retina before light exposure, but rhodopsin levels were significantly lowered in both treated groups when compared to corresponding vehicle treated control animals. Under regimen 1, at 6 hr after light exposure, both the treated and the control groups showed comparable loss of photoreceptor cells, degeneration of the photoreceptor elements and retinal pigment epithelium, but a significantly lowered level of rhodopsin in the treated group was noted. At 6 days after exposure, the outer nuclear layer thickness, and the outer and inner segments showed significant preservation in the treated group. Also in the treated group, the number of macrophages was significantly reduced and the retinal pigment epithelial (RPE) vacuolation was markedly less. However, there was no difference in rhodopsin levels. At 14 days after exposure, the outer nuclear layer thickness and rhodopsin levels of the treated rats had significantly higher values than the controls. Under regimen 2, however, at 6 days after exposure, an ameliorative effect in the RPE was observed but there were no differences of rhodopsin levels, the outer nuclear thickness and number of macrophages between the treated and control groups. Regimen 1 was associated with a significantly higher retinal level of dexamethasone when compared with regimen 2. The ameliorative effect of dexamethasone on rat retinal photic injury may be through inhibition of lipid peroxidation, in which a high retinal level of the steroid is required.

Animals↗
PubMed1992

Dominantly inherited cystoid macular edema. A histopathologic study.

BACKGROUND: Dominantly inherited cystoid macular edema was described as a clinically distinct form of macular dystrophy with an onset at approximately age 30 years with slow progression over the ensuing decades. This is the first report of the light and electron microscopic findings in two donor eyes of one of the patients with this clinical entity. METHODS: Both eyes were obtained after death and fixed within 24 hours in a buffered 4% formaldehyde-1% glutaraldehyde solution. For light microscopy, tissue was embedded in paraffin and stained with hematoxylin-eosin, periodic acid-Schiff, colloidal iron for mucopolysaccharides, and an antibody to glial fibrillar acidic protein. For ultrastructural investigation, several blocks of choroidal/retinal tissues from the posterior pole, including both maculae, were embedded in epoxy resin and processed for transmission electron microscopy. RESULTS: Major findings included large retinal cysts in the macula, atrophy and marked disorganization of the inner nuclear layer, advanced degeneration of Müller cells with nodular aggregates of basement membrane-like material, and a preretinal membrane. The retinal vasculature did not show excessive endothelial alterations but was surrounded by deposits of multilayered basement membrane in the perivascular space. CONCLUSION: The authors believe that the pathologic features of dominantly inherited cystoid macular edema are different from those of macular edema caused by other disease processes. The predominant pathologic changes affected mainly the inner nuclear layer. The possibility of a primary disease of the Müller cell is suggested.

Aged↗
PubMed1992

Therapeutic parameters of methylprednisolone treatment for retinal photic injury in a rat model.

Methylprednisolone (MP) has been prescribed for the treatment of solar retinopathy presumably because of its anti-inflammatory effect. Recently, high doses of MP have been shown to ameliorate light-induced photoreceptor degeneration, and the mechanism of action was suggested to be the inhibition of lipid peroxidation. In this study we examined the dose-response effect and the effect of delayed treatment with MP in an established rat model of retinal photic injury. Animals received intraperitoneal injections of either MP (8, 160, or 320 mg/kg/day) or saline solution (as a control) for 2 days. Injections were started simultaneously with the commencement of light exposure or delayed for 6 or 24 h. The animals were sacrificed 6 days after light exposure, and the retinal damage was assessed by light microscopy and morphometric measurement of the outer nuclear layer (ONL) thickness. Morphologically and morphometrically, treatment with 8 mg/kg/day of MP was not effective, while treatment with 160 mg/kg/day caused better preserved photoreceptors and a thicker ONL compared with the controls (P less than 0.001). Animals administered with a dose of 320 mg/kg/day showed more severe damage to photoreceptors, resulting in a thinner ONL (P less than 0.05). When treatment with 160 mg/kg/day was delayed for 6 h, a similar efficacy as in the no-delay group was noted, but when treatment was delayed for 24 h, no beneficial effect was observed (P = 0.19). Our results demonstrated that early treatment with high doses of MP ameliorated retinal photic injury in rats.

Animals↗
PubMed1992

'On' response defect in paraneoplastic night blindness with cutaneous malignant melanoma.

Response properties of rod and cone systems were assessed in a patient with an acquired form of night blindness associated with a metastatic cutaneous malignant melanoma. The night blindness, a sensation of shimmering lights, and selective reductions in the amplitudes of both rod and cone electroretinographic (ERG) b-waves were present before and after chemotherapy, confirming that this disorder was a paraneoplastic consequence of the melanoma rather than a response to chemotherapy. During ERG testing with flashes of extended duration, the cone b-wave abnormality was found to be a predominant loss of the cone ERG "on" response with relative preservation of the "off" response, similar to that observed in patients with congenital stationary night blindness. An impairment in signal transmission specific for retinal "on" pathways may be a primary defect in both of these forms of night blindness.

Adolescent↗
PubMed1991

Amelioration of light-induced retinal degeneration by a calcium overload blocker. Flunarizine.

Although free radical formation and lipid peroxidation have been implicated in photoreceptor degeneration following continuous light exposure, recent evidence led us to hypothesize that excessive stimulation of the photoreceptor cells in prolonged light exposure may cause intracellular calcium overload and consequent photoreceptor cell injury. To test this hypothesis, we studied the effects of flunarizine hydrochloride, a calcium overload blocker that inhibits the inositol 1,4,5-triphosphate-induced release of intracellular stores of calcium, in an established rat model of light-induced retinal degeneration. Light and electron microscopic examination of the flunarizine-treated retinas revealed remarkable preservation of the retinal pigment epithelium, rod inner and outer segments, nuclei, and synapses of the photoreceptor cells at all phases of the recovery period. This observation was further supported by morphometric evaluation of the outer nuclear layer thickness, which revealed a greater preservation of the photoreceptor nuclei in the drug-treated animals at 6 and 14 days after exposure. In addition, the rhodopsin levels in the flunarizine-treated retinas were also significantly higher than in the controls in all phases of recovery. The ability of flunarizine to ameliorate light-induced retinal degeneration in the rat supports our hypothesis that elevated intracellular calcium may indeed play a role in light-induced photoreceptor degeneration.

Animals↗
PubMed1991

Retinal and vitreal neovascularization in retinopathy of prematurity. A scanning electron microscopic study in the kitten.

The angioarchitecture of vitreal and retinal neovascularizations produced experimentally in the eyes of kittens aged 2 to 9 weeks was studied with scanning electron microscopy. Various forms of new retinal and vitreal vessels were observed depending on topographic locations. Intraretinal neovascularization was observed at the retinal periphery as it grew toward the avascular zone in forms of short vascular buds, aneurysmal outgrowths, and neovascular loops. Posterior or to this frond of neovascularization, intertwining intraretinal telangiectasia was observed. At the posterior pole, capillaries with microaneurysms extended posteriorly toward the deeper layers of the retina from the vascular trunks at the nerve fiber layer. Vitreal neovascularization broke through the internal limiting membrane and exhibited aneurysmal outgrowths, clusters of glomerular swellings, and sinusoidal vascular channels. At the optic disc, vitreous neovascularization took the form of aneurysmal outgrowths and long vascular buds. Vitreal neovascularization showed different characteristics from the intraretinal neovascularization. We hypothesize that the topographic variation of the angioarchitecture of retinal and vitreal neovascularizations depends on the maturity of the vessels and might be related to the hemodynamics at each site.

Animals↗
PubMed1991

A histopathologic study of retinal lesions inflicted by transscleral iontophoresis.

In the present study, retinal lesions were induced by transscleral iontophoresis (1.5 mA) in rabbits. The size and severity of the lesions increased with the duration of application (2-25 min). No lesion was noted after less than 1 min application. Immediately after 5 min iontophoresis, the edematous retina exhibited necrotic retinal pigment epithelium (RPE), loss of outer segments, and thinning of the inner and outer nuclear layers. At 5 days after iontophoresis, there was a proliferation of RPE cells and macrophages in the subretinal space, with thinning of the inner and outer retinal layers continuing. By day 14, the retina had been reduced to a glial membrane. Immediately after 15 min iontophoresis, the damaged retina appeared in a mummified form containing no cellular elements. By day 5 thereafter, macrophages and actively proliferating RPE cells had been noted in the necrotic retina. By day 14, a glial membrane had formed.

Animals↗
PubMed1991

Clearance of S-(3-amino-2-hydroxypropyl) phosphorothioate (WR-77913) in rats.

Complications of radiotherapy in the treatment of retinal and choroidal neoplastic diseases include cataract formation, radiation retinopathy, neovascular glaucoma, cystoid macular edema, and subretinal neovascularization. These side effects may be minimized by the use of compounds known to have a protective effect on normal ocular tissues without impeding the benefits of therapy. Phosphorothioates, first developed under the Antiradiation Drug Development Program of the U.S. Army Medical Research and Development Command, have been reported to protect normal tissues during radiation therapy in a variety of animal models. One of the phosphorothioates, WR-77913 (S-[3-amino-2-hydroxylpropyl]phosphorothioate) was found to inhibit cataract formation in rats after radiation exposure. To test the efficacy of WR-77913 in the retina, we established a high-pressure liquid chromatography method to measure the levels of dephosphorylated WR-77913 and studied the drug's clearance from the lens, retina, blood, kidney, and liver in rats.

Amifostine↗
PubMed1991

Antiretinal antibodies in serum of patients with age-related macular degeneration.

Antibodies, immunoreactive with normal human retinal proteins, were detected by Western immunoblot analysis in the sera of 30 patients with age-related macular degeneration (AMD). Sera from 14 of these patients demonstrated positive binding predominantly to a doublet protein of molecular weight between 58 and 62 kD. The sera from the remaining 16 patients and from 12 control subjects reacted either weakly or not at all with the doublet protein. No correlation was found with any specific type of AMD. The serum antibodies also immunocrossreacted with the same proteins from isolated photoreceptor outer segments; this was confirmed by indirect immunofluorescence on intact retinas. The crossreactivity of the serum antibodies with a protein of Mr 58 to 62 kD, the lower band present in the bovine purified neurofilament-68 kD preparation, suggests strongly that this protein may be a component of the neuronal cytoskeleton. However, it is not clear whether these autoantibodies play a direct role in the etiology of AMD or represent a nonspecific response to retinal damage.

Aged↗
PubMed1991

Desferrioxamine ameliorates retinal photic injury in albino rats.

Albino rats were given intraperitoneal desferrioxamine before exposure to intense fluorescent light. Morphometric and morphologic studies of the retina indicated that there was better preservation of photoreceptor nuclei and fewer subretinal macrophages in rats treated with desferrioxamine than in the control rats. The results of the study imply that iron and hydroxyl radicals may be important mediators in photic retinal injury.

Animals↗
PubMed1991

A pathologic study of photoreceptor cell death in retinal photic injury.

In the studies of retinal photic injury in the rat model, about 14-47% of the photoreceptor cell loss occurs in the first 24 hours. To understand the mechanism of this massive cell death and subsequent dissolution, we studied the early morphologic changes and examined the effect of cycloheximide, a protein synthesis inhibitor, on photic injury in rats. Groups of 2 dark-adapted albino Lewis rats were sacrificed immediately after 8, 16 or 24 hr of continuous exposure to green fluorescent light (intensity, 160-180 foot-candles; wavelength, 490-560 nm). An additional 2 rats were sacrificed 8 hr after a 24 hr light exposure, and 2 animals served as unexposed controls. The morphologic findings of the degenerating photoreceptor cells were assessed by light and electron microscopy. The integrity of the nuclear chromatin was investigated using a monoclonal anti-DNA antibody. Most of the photoreceptor cell loss was observed between 16 and 24 hr of exposure. No inflammatory or macrophagic cells were seen. Different stages of nuclear condensation and chromatin margination could be defined. The chromatin showed a progressive decrease in DNA labelling density. Scattered photoreceptor cells showed early cytoplasmic densification. To study the effect of cycloheximide, 4 rats were treated with 5 mg/kg subcutaneously at the start of a 24 hr exposure period and were sacrificed 6 hr after the exposure. Four untreated animals served as exposed controls for morphometric comparison of the outer nuclear layer (ONL). The control rats showed a 24% decrease in the thickness of the ONL when compared to cycloheximide-treated rats (p less than 0.001). The observations of mitochondrial changes and early DNA digestion were consistent with necrosis as the mechanism of cell death. However, in scattered photoreceptor cells, cytoplasmic densification, margination of nuclear chromatin, the lack of associated inflammation and the protective effect of cycloheximide were suggestive of apoptosis as another mechanism of cell death.

Animals↗
PubMed1991

Nimodipine, a voltage-sensitive calcium channel antagonist, fails to ameliorate light-induced retinal degeneration in rat.

A recent study demonstrated the amelioration of light-induced photoreceptor degeneration by flunarizine and suggested that the protective effect achieved by the drug may be due to the inhibition of inositol 1,4,5-trisphosphate-induced calcium release from intracellular stores or the inhibition of calcium entry through putative voltage-sensitive calcium channels. In the current study, we investigated the effect of nimodipine, a specific voltage-sensitive calcium channel blocker, in light-induced retinal degeneration to further define the factors involved in the retinal degenerative process. Morphological, morphometric, and biochemical results demonstrated that nimodipine was ineffective in ameliorating light-induced retinal degeneration, and implied that calcium entry through voltage-sensitive channels is unlikely to be involved in this disease process, and inositol 1,4,5-trisphosphate-induced calcium release from intracellular stores may play a dominant role in light-induced photoreceptor cell damage.

Animals↗
PubMed1991

A comparative study of methods of photoreceptor morphometry.

A comparative study was performed to compare methods of quantitative evaluation of damage to photoreceptor cells in rat eyes exposed to light. Using a manual count of individual photoreceptor nuclei as the standard, the following measurements were compared: (1) outer nuclear layer column count, (2) area, (3) thickness, and (4) the number of nuclei of the outer nuclear layer of the retina using a newly developed computer program that counts a digitized image. Linear-regression analysis of the data showed that the computer method was the most accurate with a Pearson correlation coefficient of 0.9911. The other methods tested also correlated well with the manual count, with coefficients ranging from 0.9367-0.9532. All these methods were reasonably accurate measurements of photoreceptor layer integrity, with the computer count most closely approximating the values obtained by a manual count. However, the outer nuclear layer thickness measurement appeared to be the fastest and most convenient method to evaluate photoreceptor cell damage quantitatively. Computer counting could be reserved for situations in which a high degree of accuracy is required.

Animals↗