Biomedical subjects

M O Tso

Publications and source records attributed to M O Tso.

At least 55 records · Page 3Linked to original sources

PubMed1995

Apoptotic photoreceptor cell death after traumatic retinal detachment in humans.

OBJECTIVE: To determine the mechanism of photoreceptor cell death after traumatic retinal detachment in humans. DESIGN: Clinical records from 1975 to 1993 of 75 patients, whose eyes were enucleated after traumatic retinal detachment, were reviewed for age, sex, previous ocular or systemic medical history, interval from initial trauma to enucleation, visual acuity, and types of trauma. The patients were divided into five groups of 15 cases each, based on the interval from initial trauma to enucleation. The retinal tissue was examined for two markers of apoptosis: (1) nicked nuclear DNA in situ by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end labeling (TUNEL) technique and (2) apoptotic bodies by light and electron microscopy. RESULTS: Of the 75 cases of ruptured globe and traumatic retinal detachment that were evaluated, 19 eyes (25.3%) showed TUNEL-positive labeling of photoreceptor cells. Nicked nuclear DNA was detected in photoreceptor cells of detached retinas as early as 8 hours after trauma. The detached retinas in seven of 15 eyes enucleated within 2 days after ocular trauma showed TUNEL-positive photoreceptor nuclei. The number of cases showing TUNEL-positive photoreceptor nuclei decreased as the interval between initial trauma and enucleation increased. The TUNEL-positive photoreceptor cells could still be seen in the detached retinas of two eyes enucleated 22 days after trauma. Light microscopy disclosed condensation and fragmentation of photoreceptor nuclei in the detached retinas. Electron microscopy showed structures resembling apoptotic bodies phagocytosed by neighboring cells in the TUNEL-positive retinas. CONCLUSIONS: Apoptosis is an important mechanism of photoreceptor cell degeneration in the early stage after traumatic retinal detachment in humans.

Adolescent↗

PubMed1995

Bilateral diffuse iris nodular nevi. Clinical and histopathologic characterization.

BACKGROUND: Diffuse nodular nevus of the iris is an uncommon condition that presents with multiple verrucous excrescences distributed diffusely on the iris surface. METHODS: The authors describe 30 patients with bilateral diffuse iris nodular nevi and report associations with bilateral congenital cataract, neurofibromatosis, oculodermal melanocytosis, congenital ptosis, morning glory anomaly, Axenfeld anomaly, or Peters anomaly. RESULTS: Iris nodules were uniform in size and distribution and were brown, as was the surrounding iris. Light and electron microscopy of iridectomy specimens from one patient showed elevated plaques composed of aggregates of plump, lightly pigmented nevoid cells interwoven with mature, densely pigmented spindle-shaped uveal melanocytes. CONCLUSIONS: The authors report the largest clinical series and first ultrastructural description of bilateral diffuse iris nodular nevi, which represents a variant of neural crest development. No ocular complications could be attributed to the iris nodules, which should be differentiated from Lisch nodules and other pathologic iris lesions.

Adolescent↗

PubMed1995

The effect of aurintricarboxylic acid, an endonuclease inhibitor, on ischemia/reperfusion damage in rat retina.

Apoptosis is a form of cell death distinct from necrosis showing distinctive morphologic features and may require energy. It is under various control mechanisms and may involve an endonuclease, which cleavages genomic DNA in the internucleosomal linker regions. Previously, we reported that ischemic/reperfusion injury to rat retina induced endonuclease mediated apoptosis of retinal neurons. In this study, we examined the effect of aurintricarboxylic acid (ATA), an endonuclease inhibitor, on ischemia/reperfusion damage in rat retina in our established rat model. A single intraperitoneal injection of ATA at 2 mg/kg given immediately after 60 minutes of ischemia to the retina showed no observable effect. At 10 mg/kg, there was notable beneficial effect morphologically but not morphometrically. ATA at 100 mg/kg showed significant effect both morphologically and morphometrically. This observation is consistent with the hypothesis that endonuclease mediated apoptosis may be involved in retinal cell loss after ischemia/reperfusion insult.

Animals↗

PubMed1995

Immunoreactivity against tau, amyloid precursor protein, and beta-amyloid in the human retina.

PURPOSE: Increased immunoreactivity (IR) of beta-amyloid and the amyloid-associated proteins tau and amyloid precursor protein (APP) in the brain have been linked to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease. However, the expression of these proteins has not been investigated in the normal or diseased human retina. METHODS: Using immunohistochemical techniques, we examined the distribution and age-related changes of anti-tau-1, anti-tau-2, anti-APP, and anti-beta-amyloid IR in the human retina at various ages (n = 24), in retinitis pigmentosa (RP, n = 6), and in age-related macular degeneration (ARMD, n = 10). RESULTS: Tau-1 immunoreactivity was intense in the inner retinal layers and did not change with age or in RP. Eyes with ARMD showed less intense staining but exhibited a similar distribution. Tau-2 IR was faint and did not change with age but was mildly increased in the retinal pigment epithelium (RPE) of eyes with RP and in the retina of eyes with ARMD. APP IR was most prominent in the ganglion cell and nerve fiber layer, and it appeared to increase in ganglion cells of older persons and in RPE cells of eyes with RP and ARMD. Beta-amyloid IR was only detected focally in sub-RPE deposits in eyes from older persons. CONCLUSIONS: The proteins investigated in this study are present in the human retina. The staining pattern of tau is different from the brain, but it shows no age-related changes. The increased immunoreactivity of APP in retinal ganglion cells of older eyes and in RPE cells of eyes with RP and ARMD, as well as the patchy staining of beta-amyloid within sub-RPE deposits, might indicate a relationship of these proteins to retinal aging and possibly to retinal degeneration in RP.

Adolescent↗

PubMed1995

TEMPOL, a superoxide dismutase mimic, ameliorates light-induced retinal degeneration.

The efficacy of 4-hydroxy-2,2,6,6-tetramethylpiperidine-l-oxyl (TEMPOL), a metal independent superoxide dismutase (SOD) mimic, in ameliorating light-induced retinal degeneration was investigated. Thirty-six Lewis albino rats were exposed to green fluorescent light (490-580 nm, 160-180 foot-candles) for 24 hr, after dark adaptation for 24 hr. The animals received six intraperitoneal (IP) injections of TEMPOL (100 mg/kg) or an equivalent volume of saline solution (vehicle-treated control groups) at 6 hr intervals starting 6 hr before the light exposure and ending 24 hr after light exposure. Another six rats were used as unexposed controls. The animals were killed at 6 hr, 6 days and 14 days after light exposure. Retinal damage was assessed by light and electron microscopy, measurements of outer nuclear layer (ONL) thickness and rhodopsin levels and counting of macrophages in the subretinal space. After light exposure, the TEMPOL-treated rats showed mild edema of the retinal pigment epithelium (RPE), less densified inner segments (IS) at 6 hr and better preserved photoreceptors at 6 days and 14 days compared with vehicle-treated control groups. Morphometrically the ONL was thicker in the TEMPOL-treated rats than in the vehicle-treated control at 6 days (p<0.01) and 14 days (p<0.05) but no significant difference occurred at 6 hr (p>0.05). Rhodopsin levels in the TEMPOL-treated rats were significantly higher at 6 days (p<0.05) but not at 6 hr (p>0.05) or 14 days (p>0.05). Our results demonstrated that TEMPOL ameliorated light-induced retinal degeneration in rats. These findings are consistent with the hypothesis that superoxide radicals may play a crucial role in mediating light-induced retinal degeneration.

Animals↗

PubMed1994

Syringocystadenoma papilliferum of the eyelid.

Syringocystadenoma papilliferum is a benign adnexal tumor of the scalp and face. We treated syringocystadenoma papilliferum in a 31-year-old man who had a circumscribed cup-shaped lesion of the left upper eyelid with a central crater. On histologic examination, the epidermal edge showed hyperkeratosis and invasive acanthosis with papillary projections that filled the central crater. The deeper portions of the projections resembled ductal structures lined by an inner columnar epithelium, which demonstrated luminal apical decapitation secretions, and an outer layer of smaller cuboidal cells. The fibrovascular dermal tissue exhibited prominent plasmacytic infiltration underlying the papillary epithelium. Although rare, syringocystadenoma papilliferum should be considered in the differential diagnosis of umbilicated squamous or basal cell tumors, especially if noted in a young individual.

Adenoma, Sweat Gland↗

PubMed1994

The effects of simultaneous occlusion of the posterior ciliary artery and vortex veins. A histopathologic study.

OBJECTIVE: In previous research, experimental occlusion of the posterior ciliary arteries resulted in an infarction of the retinal pigment epithelium and outer retina. A simultaneous occlusion of one or two vortex veins (VVs) appeared to have an ameliorative effect on the retinal infarct based on previous clinical and angiographic observations. The objectives of this report were to evaluate the histopathologic changes of the ischemic retina and to examine the disruption and healing of the blood-retinal barrier under various combinations of ciliary artery and VV occlusions. METHODS: Experimental posterior ciliary artery (PCA) occlusion with (n = 3) or without (n = 3) simultaneous VV occlusion was carried out in six rhesus monkey eyes. The eyes were enucleated over a course of 3 months. The histopathologic changes of the ischemic retina were examined by light and electron microscopy. In addition, the horseradish peroxidase tracer technique was used to study the blood-retinal barrier. RESULTS: Ischemic changes following the occlusion of the PCA consisted of coagulation necrosis of the retinal pigment epithelium and of the outer retinal layers and were less pronounced in eyes with simultaneous VV occlusion. At 6 hours after the insult, the blood-retinal barrier was broken and horseradish peroxidase leaked into the subretinal space (PCA occlusion with one VV occlusion). Three months later, the blood-retinal barrier had re-formed, even in the eyes with severe ischemic injury. CONCLUSIONS: The histopathologic changes suggest that the ameliorative effect of simultaneous VV occlusion on the effects of PCA occlusion might be due to reduced perfusion in the choroidal circulation.

Animals↗

PubMed1994

The effects of naloxone on retinal ischemia in rats.

The efficacy of naloxone (NL), a broad spectrum opioid antagonist, on retinal ischemia, was evaluated in a rat model of retinal ischemia with histopathologic and morphometric criteria. Two intraperitoneal injections of naloxone 3 mg/kg given immediately and 6 hr after reperfusion showed beneficial effects to the retina as evaluated at 2, 7, and 14 days after reperfusion. Morphologically, the naloxone-treated group showed better-preserved ganglion cells, nerve fiber layer, and inner nuclear layer. Morphometrically, in the treated groups, inner retinal thickness at all three time points and ganglion cell counts at 7 days showed higher values than vehicle controls. This beneficial effect of naloxone was dose-dependent with a minimal effective total dose of 6 mg/kg. A possible role of opiate receptors in retinal ischemia is suggested.

Animals↗

PubMed1994

Intravitreal delivery of ganciclovir in rabbits by transscleral iontophoresis.

To avoid the side effects of systemic administration of ganciclovir (GCV) for the treatment of cytomegalovirus (CMV) retinitis, we studied transscleral iontophoresis of GCV into rabbit eyes. After a single application with 20% (w/w) aqueous solution of GCV at 1.0 mA for 15 min gave a vitreal/retinal level of GCV at 74 +/- 17 micrograms/ml at 2 hours as determined by HPLC. At 24 hours after iontophoresis the vitreal/retinal level was above therapeutic level at 4.2 +/- 0.6 micrograms/ml. At 72 hours, there was still detectable level in the vitreous/retina. Hence, transscleral iontophoresis is able to deliver effective dose of GCV into the vitreous. Multiple applications of iontophoresis should be examined as a possible means of CMV treatment.

Animals↗

PubMed1994

Injuries induced by diffuse photodynamic action in retina and choroid of albino rats. Morphologic study of an experimental model.

BACKGROUND: The morphologic changes of the retina, choroid, and respective vasculatures in an experimental model of diffuse photothrombosis and photodynamic injury were studied. METHODS: After intravenous injection of rose bengal (40 mg/kg), eyes of 21 albino rats were exposed to a light intensity of 15-17,000 ft-cd for 2 to 15 minutes. Survival times ranged from 15 minutes to 6 days. The specimens were studied by light and electron microscopy. RESULTS: Photothrombosis of retinal and choroidal vessels was variable in extension and duration. Vascular lesions included vacuolation and sloughing off of endothelium, and necrosis and apoptosis of pericytes and smooth muscle cells. Retinal and choroidal injuries exhibited considerable regional and structural differences, such as predominance in the outer versus inner retina, or focal versus diffuse injury. CONCLUSION: Damage produced by this model was irregular in extent and character, due to several hard-to-control parameters. It was presumably due not only to ischemia but also to free radical chain reactions initiated by photodynamic action. This model may not be suitable for rapid quantitative assessment of ischemic retinal injury, but it provides opportunities for the investigation of pathophysiologic mechanisms.

Animals↗

PubMed1994

Correlation of phospholipid hydroperoxide glutathione peroxidase activity to the sensitivity of rat retinas to photic injury.

We hypothesize that the differential susceptibility to photic injury among different strains of rat retinas may depend on the levels of phospholipid hydroperoxide glutathione peroxidase (PHGPX) activity, one of the endogenous antioxidant enzymes in the retina. The retinas of four inbred strains of albino rat (Fischer, Wistar, Buffalo and Lewis) were analyzed for glutathione peroxidase activity using H2O2, cumene hydroperoxide, and phospholipid hydroperoxide as assay substrates. In all four strains of rat, PHGPX was observed only in the high salt extract of the retina, while peroxidases determined by H2O2 or cumene hydroperoxide were observed mainly in the low salt extract. PHGPX was highest (66.7 mU/mg) in the most light-resistant Fischer strain and lowest in the most light-sensitive Lewis strain (31.9 mU/mg), while the activity levels in the moderately light-sensitive Buffalo and Wistar strains were 46.6 and 38.5 mU/mg, respectively. In contrast, there was no significant difference in peroxidases determined by H2O2 or cumene hydroperoxide among the four strains. These observations suggested that, in rat retina, the membrane-associated PHGPX may have an important role in the defense against light-induced free radical damage.

Animals↗

PubMed1994

Effects of basic fibroblast growth factor in retinal ischemia.

PURPOSE: Basic fibroblast growth factor (bFGF), a 17- to 24-kDa protein known to be essential for the survival of neurons, induced fiber outgrowth of ganglion cells in cultures of rat retina and rescued photoreceptor cell loss in the retina of Royal College of Surgeon rats. The authors evaluated the efficacy of bFGF in rescuing the neuronal loss in rat retina after retinal ischemia. METHODS: Retinal ischemia was induced in 29 eyes of 17 albino Lewis rats by increasing the intraocular pressure to 110 mm Hg for 45 minutes via an intracameral catheter. A total of 800 ng of bFGF was delivered into the anterior chamber at the time of induction of ischemia. Sixteen eyes of nine rats received bFGF, and 13 eyes of eight rats received heparin in phosphate-buffered saline as vehicle control. The animals were euthanized 7 or 14 days after reperfusion. RESULTS: Morphologic examination of the retinas at both time points showed that necrosis of the retinal ganglion cells (RGCs) and thinning of the inner plexiform and inner nuclear layers were less severe in the bFGF-treated eyes than in the vehicle-treated eyes. On morphometric examination, 7 days after reperfusion, the mean thickness of the inner retinal layers and the RGC counts on flat preparations of retina in both the posterior and the peripheral portions of the retina were significantly higher in the bFGF-treated eyes than in the vehicle-treated eyes (P < 0.02). At 14 days, similar beneficial effects were noted in all morphometric parameters, except RGC counts in the posterior pole. CONCLUSIONS: These results demonstrate that bFGF partially protects the RGCs and other inner retinal elements from ischemic injury.

Animals↗

PubMed1994

Apoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats.

PURPOSE: To determine the pathogenetic mechanism of photoreceptor cell degeneration in the inherited retinal dystrophy in Royal College of Surgeons (RCS) rats. METHODS: The dystrophic retinas of the pink-eyed RCS (RCS-rdy-p) rats were examined for DNA fragmentation by agarose gel electrophoresis of retinal DNA and by TdT-mediated biotin-dUDP nick-end labeling (TUNEL) in paraffin sections. Rats ranging in age from 3 to 60 days were examined. RESULTS: Agarose gel electrophoresis of retinal DNA isolated from animals 25, 30, 35, and 40 days old showed a ladder pattern of degradation with bands corresponding to multiples of 180 to 200 base pair subunits. TUNEL study showed increasing labeling of photoreceptor cells with progression of the retinal dystrophy of the RCS rats. CONCLUSIONS: Apoptosis is the dominant mechanism of photoreceptor degeneration in the RCS rat, which has a genetic defect in the phagocytic activity of retinal pigment epithelium. The onset of the degeneration appeared to vary between rod cells in the different regions of the eye.

Animals↗

PubMed1993

Diffuse corneal clouding in siblings with fetal alcohol syndrome.

Three of four siblings born to parents with a history of heavy alcohol abuse had bilateral diffusely cloudy corneas at birth. These three siblings, who had mild systemic features of fetal alcohol syndrome, underwent corneal transplantations, and their specimens were examined by light and electron microscopy. Histologically, the alterations in Bowman's layer ranged from thickening to total loss. There were varying degrees of corneal stromal edema. The unique pathologic feature in the corneas was the anomaly of the anterior banded zone of Descemet's membrane, which was either absent, poorly formed, or thinned in the central and peripheral cornea. The corneal endothelium was attenuated or multilayered. The diffuse clouding and the range of histologic abnormalities in the corneas might be related to the maternal alcohol abuse.

Child, Preschool↗

PubMed1993

Amelioration of retinal photic injury by a combination of flunarizine and dimethylthiourea.

Free radical scavengers and a calcium overload blocker have been demonstrated separately to ameliorate light-induced retinal degeneration, suggesting that both free radical formation and increased intracellular calcium levels are involved in the pathologic changes of this disease process. To understand the relationship between these two mechanisms, we studied the ameliorative effects of combined treatment with flunarizine and dimethylthiourea as well as individual treatment with either drug in a rat model of light-induced retinal degeneration. At 6 hr and 6 and 14 days after light exposure, morphologic and morphometric studies of the retinas from the rats receiving the combined treatment demonstrated better-preserved retinal pigment epithelial cells, photoreceptor elements, and nuclei than did retinas from rats receiving treatment with either flunarizine or dimethylthiourea alone. Rhodopsin level measurements at 6 and 14 days further substantiated the results of the protective effects on the photoreceptor outer segments. Because we used a saturating dose for dimethylthiourea, the enhanced ameliorative effect of the combination treatment suggested that free radical formation and elevated intracellular calcium levels were two separate mechanisms in light-induced retinal degeneration.

Animals↗

PubMed1993

An immunohistochemical study of opsin in photoreceptor cells following light-induced retinal degeneration in the rat.

Light-induced retinal degeneration has been hypothesized to be rhodopsin-mediated. However, the alterations induced in the opsin moiety of the rhodopsin molecule and its distribution in the rod cell after a photic insult have not been definitively established. We used light and electron immunohistochemistry to study the alterations in retinal opsin immunoreactivity in a rat model of retinal photic injury. In normal unexposed rat retinas, opsin immunoreactivity was restricted to the rod outer segments. At 6 h after a 24-h light exposure, opsin immunoreactivity was present in the rod outer segments in both the superior and inferior retina, but in addition marked immunoreactivity was present in the inner segments in the superior quadrant of the light-damaged retina. At 6 days after exposure, intense immunoreactivity was noted around the severely degenerating rod nuclei and inner segments. However, at 21 days following light exposure, opsin immunoreactivity in areas of recovery was again restricted to the short regenerated rod outer segments. It appears that, despite severe light-mediated retinal degeneration, anti-opsin immunoreactivity persisted in the photoreceptor cells but with an altered pattern in damaged rod outer segments and photoreceptor perikarya. However, opsin immunoreactivity relocated to the regenerated rod outer segments in the recovery phase.

Animals↗

PubMed1993

Methylprednisolone therapy in laser injury of the retina.

The efficacy of methylprednisolone in argon-laser-induced retinal injury in primates was evaluated by clinical, histopathologic, and morphometric criteria. Methylprednisolone was given with a loading dose of 30 mg/kg followed by 5.4 mg/kg per hour in three different regimens: (1) starting 24 h before laser and continuing for 4 days; (2) starting immediately after laser and continuing for 4 days; and (3) starting immediately after laser and continuing for 8 h. Fundus photography, fluorescein angiography, and histologic examination showed significant beneficial effects of all three treatments compared to controls. Morphometrically, at the center of the lesion, the width of disrupted outer nuclear layer, the width of the affected RPE, and the percentage of residual photoreceptor nuclei confirmed the efficacies of treatment regimens 1 and 2, but not treatment regimen 3.

Animals↗

PubMed1993

Tau-2 immunoreactivity of corpora amylacea in the human retina and optic nerve.

PURPOSE: To characterize the constituents of corpora amylacea in the human retina and optic nerve. METHODS: Immunohistochemistry was performed on sections of retina, optic nerve, and brain tissue using antibodies against tau 1, tau-2, and amyloid precursor protein. RESULTS: Consistent anti-tau-2 immunoreactivity was noted in the corpora amylacea in the retina, optic nerve, and brain tissue, albeit with variations in pattern and intensity of staining. No immunoreactivity was observed with antibodies anti-tau 1 and anti-amyloid precursor protein. CONCLUSION: Our findings suggest the accumulation of possibly abnormal tau-2 within the corpora amylacea, which may be either astrocytic or axonal in origin.

Adult↗