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Biomedical subjects

S E Nilsson

Publications and source records attributed to S E Nilsson.

At least 19 recordsLinked to original sources
PubMed1996

Lipofuscin formation in cultured retinal pigment epithelial cells exposed to photoreceptor outer segment material under different oxygen concentrations.

Lipofuscin accumulates in the course of time in the acidic vacuolar apparatus of retinal pigment epithelial (RPE) cells and may influence their metabolic functions. In order to study the effect of oxidative stress on lipofuscin accumulation, rabbit RPE cell cultures were kept at an ambient oxygen concentration of either 8% or 40%. To simulate the normal phagocytic function of RPE cells, bovine photoreceptor outer segments (POS) were added daily. The lipofuscin-specific autofluorescence was measured after 1, 2 and 3 weeks. RPE cells cultured under normobaric hyperoxic conditions (40% oxygen) showed significantly higher levels of lipofuscin-like autofluorescence than those kept under normobaric and probably normoxic conditions (8% oxygen) after 1 (p = 0.0050), 2 (p = 0.0001) as well as 3 (p = 0.0077) weeks. At both oxygen concentrations, the lipofuscin accumulation level was increased after 2 weeks of POS exposure (40% p = 0.0001; 8% p = 0.0037) and even further after 3 weeks (40% p = 0.0541; 8% p = 0.0377). The results suggest an involvement of oxidative mechanisms in the formation of lipofuscin from phagocytized POS by RPE cells. The autofluorescence of control cells, not exposed to POS, was significantly (40%: 1 week p = 0.0011, 2 weeks p = < 0.0001, 3 weeks p = 0.0001; 8%: 1 week p = 0.0036, 2 weeks p = 0.0063, 3 weeks p = 0.0066) lower than that of the POS-fed cells. The autofluorescence increased significantly (40% p = 0.0059; 8% p = 0.0034) between week 1 and week 3 in the control cells. This finding may reflect a contribution to lipofuscin formation by autophagocytized intracellular material. The present model seems to be useful for further studies on the mechanisms behind lipofuscinogenesis of RPE cells as well as the possible effects of lipofuscin accumulation on cell functions and viability.

Animals↗
PubMed1996

Formation of lipofuscin in cultured retinal pigment epithelial cells exposed to pre-oxidized photoreceptor outer segments.

Accumulation of lipofuscin in the retinal pigment epithelium (RPE) with increasing age may affect essential supportive functions for the photoreceptors. Earlier, we described a model system for the study of lipofuscinogenesis in RPE cell cultures and showed that mild oxidative stress enhances lipofuscin formation from phagocytized photoreceptor outer segments (POS). In the present study, bovine POS were photo-oxidized, and turned into a lipofuscin-like material, by irradiation with UV light. Transmission electron microscopy of irradiated POS showed loss of the normal stacks of the disk membranes with conversion into an amorphous osmiophilic electron-dense mass. The formation of thiobarbituric acid reactive substances (TBARS), estimated during the irradiation process, indicated lipid peroxidation. Irradiated POS also showed a strong granular yellow autofluorescence. RPE cell cultures, kept at 21% ambient oxygen, were fed daily for 3, 5 or 7 days with either (i) UV-peroxidized POS, (ii) native POS or (iii) culture medium only. RPE cells fed irradiated POS showed significantly higher levels of lipofuscin-specific autofluorescence compared to cells exposed to native POS after 3 days (p = 0.0056), 5 days (p = 0.0037) and 7 days (p = 0.0020), and to the non-exposed control cells (3 days: p = 0.005, 5 days: p = 0.0037, 7 days: p = 0.0094). The lipofuscin content of cells exposed to irradiated POS increased significantly between days 3 and 7 (p = 0.0335). Ultrastructural studies showed much more numerous and larger lipofuscin-like inclusions in RPE cells fed irradiated POS compared to cells exposed to native POS. In the control cells, lipofuscin-like granules were small and sparse. It appears that exposing RPE cells to previously peroxidized POS, thus artificially converted to lipofuscin and obviously not digestible by the lysosomal enzymes, accelerates the formation of severely lipofuscin-loaded cells. The results will be useful for further studies of possible harmful effects of lipofuscin in heavily loaded RPE cells.

Animals↗
PubMed1995

Neuronal ceroid lipofuscinosis in the Polish Owczarek Nizinny (PON) dog. A retinal study.

Visual dysfunction and neurological symptoms were found in Polish Owczarek Nizinny (PON) dogs. Two dogs were examined, one at 2 years of age and the other one at 4 years. The oldest dog was totally blind. The 2-year-old dog developed mental disturbances and the 4-year-old dog became severely ataxic. Ophthalmoscopical findings were retinal hyper-reflectivity, attenuation of the retinal vessels and the presence of greyish to brown spots in the fundus. Electrophysiological and ultrastructural studies were performed in the 2-year-old dog. Scotopic ERG responses were absent, whereas 30 Hz cone flicker responses were recordable, although with an amplitude reduced to about 30% of the normal level. A slow negative potential replaced the c-wave, indicating a dysfunction of the RPE. Intracellular inclusions with a granular appearance or containing membranous fingerprint-like or curvilinear profiles, resembling ceroid, were found in different retinal cells. The RPE cells in the central areas were charged with autofluorescent material having similar structure, Photoreceptor degeneration was most severe in the central areas, corresponding to the RPE changes. It appears than the PON dog may provide a new animal model for neuronal ceroid lipofuscinosis.

Animals↗
PubMed1995

Colour contrast sensitivity in patients with soft drusen, an early stage of ARM.

The present institutional study was undertaken in order to determine whether testing of colour contrast sensitivity is valuable in detecting early functional changes in patients at initial stages of age-related maculopathy (ARM). The study included 27 patients with soft drusen as an early sign of ARM and 29 age-matched normals. The area occupied by drusen was determined using a computer program. Colour contrast sensitivity was measured with a computer graphics system. Visual acuity, central visual field (Humphrey Field Analyser) and colour vision (D-15 panel) were normal in both groups. Mean colour contrast sensitivity was significantly lower in patients with early ARM (for the protan axis: p = 0.00019, for the deutan axis: p = 0.000078 and for the tritan axis: p = 0.000096) than in the controls. Interindividual variations were large. There was a tendency towards a bimodal distribution for all three colour axes, most evident for the tritan axis. We found a correlation of the drusen area with the protan and deutan thresholds for the fundus colour photographs r = 0.5 (p < 0.01) and r = 0.4 (p < 0.05), respectively, and with the tritan threshold for the angiograms r = 0.5 (p < 0.05). The findings suggest that colour contrast sensitivity may offer an additional possibility of predicting exudative ARM. Whether the patients with the highest thresholds are those who will be the first to show progression with indications of exudative ARM is not yet known. The patient group will be followed up in order to elucidate this question.

Aged↗
PubMed1995

Ultrastructural visualization of lectin receptors in normal and injured epithelium of the rabbit cornea.

Lectin receptors of the rabbit corneal epithelium were investigated ultrastructurally using gold-conjugated lectins. Corneal epithelium with an intact mucous layer was readily labeled with wheat-germ agglutinin (WGA), whereas after mechanical or chemical removal of the mucus, labeling was minimal, suggesting that the lectin receptors were located mainly in the mucus. Corneal epithelium subjected to slight superficial injury was also labeled with WGA. In this case, however, the gold particles were in close contact with the cell membrane of injured and/or newly exposed cells. In the more injured cells, gold particles were seen in the cytoplasm as well. Labeling with WGA indicates the presence of sialyl residues, known to be attachment sites for Pseudomonas aeruginosa. The results suggest a protective role of mucus against infection. The association of WGA lectin receptors with the plasma membrane of compromised corneal epithelial cells may help to explain the mechanism of bacterial invasion of the cornea, e.g., in overnight wear of contact lenses with insufficient oxygen transmissibility.

Animals↗
PubMed1995

Effects of argon (green) laser treatment of soft drusen in early age-related maculopathy: a 6 month prospective study.

AIM: To evaluate whether perifoveal laser photocoagulation of soft drusen reduces the total area occupied by drusen. METHOD: In a prospective, randomised study, 20 patients (mean age 71.3 (SD 7.7) years) with early age-related maculopathy (ARM) in the form of soft drusen and pigmentary changes and with good visual acuity (0.94 (0.09)) were treated with argon green laser photocoagulation. Mild laser burns (200 microns) were placed within a temporal horseshoe-shaped area, extending from a distance of no less than 500 microns from the centre of the fovea to the vascular arcades. They were placed on the drusen and scattered over areas where no drusen were present. Fundus colour photography and fluorescein angiography were performed at study entry as well as after 3 and 6 months. Nineteen age-matched patients (68.5 (6.2) years) with soft drusen maculopathy (visual acuity 0.95 (0.10)) were followed as a control group. Using a computer system, the area occupied by drusen was determined as a portion of the total area of a circle with a radius corresponding to 1250 microns in the fundus for the angiograms and 2500 microns for the colour photographs, respectively. At study entry, the mean area occupied by drusen in the treatment group was not significantly (p > 0.5-0.7) different from that of the control group. RESULTS: The mean drusen area of the angiograms and fundus colour photographs in the treated group decreased significantly from 19.3% to 13.8% (p = 0.002) and from 7.84% to 5.02% (p = 0.005), respectively. In the untreated group, the mean area occupied by drusen increased significantly from 17.4% to 20.4% (p = 0.030) and from 8.33% to 9.23% (p = 0.002), respectively. No significant changes in visual acuity (p > 0.05-0.5) or in visual fields (p > 0.05-0.3) occurred in either of the two groups during 6 months. CONCLUSION: The study suggests that the area occupied by soft drusen in patients with early ARM decreases after perifoveal laser photocoagulation but increases in an untreated control group.

Aged↗
PubMed1995

Accumulation of lipofuscin within retinal pigment epithelial cells results in enhanced sensitivity to photo-oxidation.

Retinal pigment epithelial (RPE) cells are largely postmitotic. They continuously phagocytose the outer tips of the photoreceptor outer segments (POS). Over the life span of an individual, this activity results, although surprisingly slowly, in the intralysomal accumulation of lipofuscin, or age-pigment. Native lipofuscin shows orange-red autofluorescence when exposed to blue light. The loss of energy resulting from the conversion of excitatory blue light into emitted orange-red light may induce photo-oxidative reactions. We exposed neonatal rabbit RPE cells in culture to purified POS from cow eyes. The material were either native or peroxidized by irradiation with UV-light before being added to the RPE cultures. Lipofuscin accumulation was studied by transmission electron microscopy and measured by microfluorometric registration of its autofluorescence. Cells exposed to peroxidized POS accumulated much more lipofuscin than those exposed to native POS, indicating that peroxidized outer segments are not digestable by lysosomal enzymes. Furthermore, lipofuscin-loaded RPE cells were considerable more sensitive to visible blue light than unloaded control cells. The former ones showed lysosomal membrane destabilization with ensuing leakage of lytic enzymes and eventually cell death. We suggest that photo-oxidation of lysosomal membranes surrounding accumulated lipofuscin may be of importance for the development of age-related macular degeneration.

Aging↗
PubMed1994

An early decrease in interphotoreceptor retinoid-binding protein gene expression in Abyssinian cats homozygous for hereditary rod-cone degeneration.

Levels of interphotoreceptor retinoid-binding protein (IRBP) protein and message in retinas of Abyssinian cats homozygous for progressive rod-cone degeneration were determined at early ages, well before the onset of clinical retinal degeneration. IRBP gene expression was assessed by immunochemical quantitation of IRBP protein, and by Northern blotting and slot-blotting of total RNA using a human IRBP cDNA probe. Morphology was assessed by electron microscopy and immunocytochemistry. Levels of both IRBP protein and message in affected Abyssinian cat retinas were significantly reduced below normal as early as 4 weeks of age at the earliest stage of retinal disorientation. Opsin mRNA was more abundant in affected Abyssinian cat retinas than in control retinas. This was at least 1 year before the onset of clinical symptoms. The reduction in IRBP gene expression to levels significantly below normal well before the onset of retinal degeneration in affected Abyssinian cat retinas indicates that this represents a primary defect or at least an early problem that could itself cause adverse effects.

Animals↗
PubMed1994

Slowly progressive changes of the retina and retinal pigment epithelium in Briard dogs with hereditary retinal dystrophy. A morphological study.

Seven eyes from 2 generations of Briard dogs (5 weeks--7 years old) with congenital night blindness and (in the second generation) impairment of day vision to varying degrees, were examined by light and electron microscopy. Specimens from 4 locations were studied: the central area, the midperiphery of the tapetal area, the upper periphery and the lower periphery. Disorientation of rod outer segment disc membranes was seen in the 5-week-old dog. Large electron-lucent inclusions were found in the RPE at 3.5 months of age. These inclusions occurred most frequently in the central and midperipheral-tapetal areas and seemed to increase in numbers and spread towards the periphery with increasing age. The content of these inclusions is not elucidated. Rod photoreceptor degeneration was apparent from 7 months of age and was most prominent in the peripheral areas. The cones were better preserved. The 7-year-old dog showed reduction of photoreceptors in the central and midperipheral-tapetal areas and almost complete photoreceptor degeneration in the periphery. This dog also showed severe changes of the inner retina in the peripheral fundus. It appears that these Briard dogs suffer from a very slowly progressive retinal degeneration, in which the photoreceptor degenerative changes do not correlate anatomically to the changes in the RPE cells. The disease seems to be different from the retinopathy described in the English Briards. It is not clear yet whether the lipid type of retinopathy found in American Briards is identical to the present disease.

Animals↗
PubMed1994

The annualized incidence of contact lens induced keratitis in Sweden and its relation to lens type and wear schedule: results of a 3-month prospective study.

All cases of contact lens induced keratitis (epithelial defects with an underlying infiltrate or ulcer) among cosmetic wearers in Sweden were collected in a 3-month prospective study and analyzed for risk factors in relation to lens type and wear schedule. Every ophthalmologist in Sweden was invited to participate and 100% responded. Viral cases were excluded. The number of lens wearers in Sweden, subdivided by lens type and wear schedule, was obtained in a parallel 3-month study among 71% of the lens fitters, who counted all their wearers, recording lens type and wear schedule as well as revisit and replacement schedules. The annualized incidence per 10,000 wearers was 1.48 for daily wear of rigid gas permeable lenses, 2.16 for daily wear and 10.00 for extended wear of disposable soft lenses, and 2.17 for daily wear and 13.33 for extended wear of conventional soft lenses. Thus, extended wear was associated with a significantly (P < 0.01-0.001) higher (5-6 times) risk of keratitis than daily wear. There were no other significant differences between the incidence figures. The Swedish incidence figures were approximately half as high as those reported in the U.S. Of the lesions, only 12% were located within the pupillary area and only 8% were corneal ulcers. Only three patients (12%) suffered a decrease in visual acuity. Severe keratitis was significantly (P < 0.01) more common among conventional soft lens wearers (accounting for all ulcers, all lesions within the pupillary area, and all decreases in visual acuity) than among wearers of disposable lenses.

Adult↗
PubMed1994

The hospitalized cases of contact lens induced keratitis in Sweden and their relation to lens type and wear schedule: results of a three-year retrospective study.

All hospitalized cases of contact lens induced keratitis with stromal involvement among cosmetic wearers in Sweden over a 3-year period were reviewed for risk factors in relation to lens type and wear schedule. Information on every case was obtained from ophthalmology departments. Lens type and wear schedule were identified. The number of lens wearers, subdivided by lens type and wear schedule, was obtained from a study by the Swedish Contact Lens Association. Annual incidence figures were then calculated as expressions of risk factors. There were 30.7 cases per year, on average, of hospitalized lens induced keratitis in Sweden. The annual incidence per 10,000 wearers was 0.51 for daily wear and 3.12 for extended wear of conventional soft lenses, 0.16 for daily wear and 4.17 for extended wear of disposable soft lenses, and 1.21 for daily wear of rigid gas permeable lenses. It may be concluded that daily wear of disposable lenses was associated with significantly (P < 0.05-0.01) less risk of hospitalized keratitis than daily wear of the other lens types. Extended wear of conventional and disposable soft lenses showed a significantly (P < 0.01-0.001) higher risk of hospitalized keratitis than daily wear. However, the two extended wear groups did not differ significantly (P > 0.2). Microbial keratitis was significantly (P < 0.001) more common than sterile (no growth of microbes) keratitis among conventional soft lens wearers, whereas the opposite was true (P < 0.05) among disposable lens wearers.

Acanthamoeba Keratitis↗
PubMed1993

Interaction of PhXA41, a new prostaglandin analogue, with pilocarpine. A study on patients with elevated intraocular pressure.

OBJECTIVE: To evaluate the effects of PhXA41, a new prostaglandin analogue, on the intraocular pressure (IOP) in patients receiving pilocarpine treatment and the effects of pilocarpine in patients receiving PhXA41 treatment. DESIGN: Twenty patients with ocular hypertension were randomized into two parallel groups. The treatment period was 2 weeks. Ten patients in group 1 were given PhXA41 twice daily during week 1 and, in addition, pilocarpine three times daily during week 2. Ten patients in group 2 received pilocarpine three times daily during week 1 and PhXA41 twice daily in addition during week 2. PhXA41 was used in a concentration of 0.006%, and pilocarpine was given in a concentration of 2%. MAIN OUTCOME MEASURES: In group 1, the mean IOP on day 0 was 25.1 mm Hg; on day 7, 19.1 mm Hg; and on day 14, 17.6 mm Hg. In group 2, the mean IOP on day 0 was 23.8 mm Hg; on day 7, 20.4 mm Hg; and on day 14, 17.7 mm Hg. RESULTS: PhXA41 had a clinically significant IOP-lowering effect (23.4% reduction on day 7 as compared with baseline day (P < .001). The corresponding value with pilocarpine was 14.3% (P < .001). When pilocarpine was added to PhXA41, the additional IOP reduction was 7.4% (P < .01) compared with 14.2% (P < .01) when PhXA41 was added to pilocarpine. The two groups were found to have an almost equal reduction in IOP on day 14 (group 1, 29.4%; group 2, 26.6%). No serious adverse reactions were seen. Some conjunctival hyperemia in the PhXA41-treated eyes was noted on day 7, as compared with the pilocarpine-treated eyes, but there were few complaints of discomfort. CONCLUSIONS: This study indicated that PhXA41 could be useful in the treatment of glaucoma, as monotherapy, or in certain cases in combination with pilocarpine.

Aged↗
PubMed1992

Dose response and duration of action of dorzolamide, a topical carbonic anhydrase inhibitor.

The multiple-dose, dose-response relationship and duration of action of the novel topical carbonic anhydrase inhibitor dorzolamide (previously known as MK-507) were investigated in a double-masked, randomized, placebo-controlled, parallel study in 73 patients with bilateral primary open angle glaucoma or ocular hypertension. Dorzolamide (0.7%, 1.4%, or 2%) or placebo was administered every 12 hours for 5 days and then every 8 hours for 7 days. Intraocular pressure was investigated with multiple 12-hour diurnal curves. All concentrations of dorzolamide demonstrated substantial lowering of intraocular pressure throughout the day when given twice daily (9% to 21%) or three times daily (14% to 24%). Although a dose-dependent response was observed immediately following the first dose, there were no significant differences between concentrations or dose response at either the twice or three times daily dosing regimen. Three times daily administration of 2% dorzolamide demonstrated a mean percent decrease in intraocular pressure of 18% to 22% throughout the day (mean decrease, 4.5 to 6.1 mm Hg). Dorzolamide appears to have substantial potential in the treatment of glaucoma and ocular hypertension.

Administration, Topical↗
PubMed1992

Ultrastructural changes of the retina and the retinal pigment epithelium in Briard dogs with hereditary congenital night blindness and partial day blindness.

The offspring of two Briard dogs (brother and sister) with congenital, clinically stationary night blindness showed an aggravation of the disease with severe impairment of day vision in addition to night blindness. This ultrastructural study was performed on four such second generation puppies at the age of 4 months. The neuroretina and retinal pigment epithelium (RPE) from four locations were studied: the central area (immediately temporal to the optic disc); the centre of the tapetal area; the upper periphery (border of tapetal area); and the lower periphery (non-tapetal area). The RPE showed large inclusions, seemingly lipid in nature, mainly in the central and tapetal areas of the retina. Small, membrane bound, electron-dense inclusions were scattered in the RPE cytoplasm in all areas examined. The small inclusions were found to be less numerous in normal than in affected dogs and may be lysosomal in nature. Forty to fifty percent of the rod outer segments in the tapetal area showed disorientation of the disc membranes, whereas the corresponding figures were 20-40% in the central and lower peripheral areas and 6-25% in the upper peripheral area. No structural abnormalities were found in the rod inner segments or synaptic bodies. The cones were better preserved. The inner retina appeared normal. These electron microscopic findings seem to correspond to a previously published electrophysiologic evaluation, indicating a defective and delayed rod function (virtually no scotopic a- and b-waves), a better preserved cone function (photopic flicker responses present, although reduced) and impaired RPE activity (a prominent, slow negative potential of long latency at the site of the c-wave). It appears that these Briard dogs, showing structural changes of the rod outer segments in addition to pigment epithelial inclusions, mainly located in the posterior pole, comprise a pigment epitheliopathy and retinopathy morphologically different from other hereditary canine retinopathies that have been described earlier in the literature and different from animal models of congenital night blindness.

Animals↗
PubMed1992

Changes in the DC electroretinogram in Briard dogs with hereditary congenital night blindness and partial day blindness.

Five Briard dogs, 7-12 months old, with congenital night blindness and severely reduced day vision (offspring of a sister and brother with congenital and supposedly stationary night blindness but with normal or nearly normal day vision) and three normal control dogs were studied by means of direct current (DC) electroretinography in order to analyse fast and slow retinal and pigment epithelial (RPE) potentials. No definite a- and b-waves were seen in the affected dogs in the dark-adapted state, which indicates severely impaired rod function. All affected dogs responded to 30 Hz flickering light in the light-adapted state, although with an amplitude reduced by 50-70%. Thus, cone function was better preserved than rod function. The control dogs showed a small c-wave and a deep negative trough between the b- and c-waves, indicating that slow PIII from the Müller cells, as well as the photoreceptor potential, are very prominent. In the affected dogs, there was no c-wave, but from a stimulus intensity of 3 log U above the normal b-wave threshold, a slow negative potential appeared, the latency and peak time of which were very long, 5-7 and 11-15 sec, respectively. With increasing stimulus intensities, both parameters decreased substantially, whereas the amplitude increased to a maximum of 2400 microV. In the light-adapted state, the dog with the best day vision showed a negative potential of short duration (peak time about 0.2 sec), followed by a positive potential (peak time about 1.2 sec).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Photoreceptor degeneration and loss of immunoreactive GABA in the Abyssinian cat retina.

GABA (gamma-amino butyric acid) and its synthesizing enzyme, GAD (glutamate decarboxylase; EC 4.1.1.15) were localized in the retina of Abyssinian cats homozygous for a recessively inherited retinal degenerative disorder which in several respects is similar to the human disease, retinitis pigmentosa. Clinically normal mongrel cats and heterozygous Abyssinian cats were studied for comparison. The GABA and GAD immunoreactive neurons of the heterozygous or young homozygous (clinically unaffected animals) had the same distribution and morphology as normal mongrel European type cats. The neuronal GABA immunoreactivity in both the inner and outer parts of the retina gradually disappeared in the course of the disease, with little or no loss of GAD immunoreactive neurons. Early in the disease, the changes were most severe in patches in the mid periphery of the eye and then spread both centrally and peripherally. Loss of photoreceptors was a prerequisite for the loss of GABA immunoreactivity. The observations show that retinal changes are not limited to the photoreceptors. The GABA loss is not likely to be due to a loss of neurons, because of the persistence of GAD immunoreactive neurons.

Animal Husbandry↗