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The functional and electrophysiological similarities in the changes in the electroretinogram (ERG) of man and cat affected by hereditary retinal degenerative disease were studied. The results of a series of log intensity-amplitude studies in a group of young affected Abyssinian cats were fitted to the Naka-Rushton relationship by means of a mathematical package on the University of London mainframe. The analysis showed that the amplitude of the maximum dark-adapted b-wave was significantly reduced by the end of the period studied but that the value of k, a variable inversely equivalent to retinal sensitivity, was only slightly reduced by the retinal degenerative process. The electrophysiological findings thus are similar to those found in cases of human diffuse dominantly inherited retinitis pigmentosa. [ABSTRACT FROM PUBLISHER]

Congenital stationary night blindness (CSNB), apparently inherited in an autosomal recessive manner, was observed in a litter of Briard dogs in Sweden. Of nine litter mates five had nyctalopia. The results of different clinical tests, including electroretinography (ERG), were compared with the results found in four human cases of CSNB, three of which were most probably associated with autosomal recessive inheritance and one with X-linked inheritance. The congenital and stationary nature of the disease, ophthalmoscopically normal appearing fundi, and recordable but reduced photopic flicker responses were some of the similarities found between canine and human cases. The single-flash ERG response was abnormal in the humans as well as in the affected Briards. However, the human cases showed a "negative' ERG, whereas in the Briards both the a and b waves were extremely reduced and present only at a photopic level. Cases similar to these Briards have been described also in man, where rhodopsin concentration and regeneration were found to be normal, suggesting a disturbed transduction mechanism. It thus appears that the Briard dog may become a valuable model of human CSNB. [ABSTRACT FROM PUBLISHER]

DC-recorded electroretinography (ERG) and direct recordings of the standing potential (SP) were performed on a group of normal cats and Abyssinian cats affected by a hereditary retinal degenerative disease with similarities to human retinitis pigmentosa. A significant reduction of a- and b-wave amplitudes was found at an early stage of disease at a time when there were no major alterations in the c-wave and SP. At later stages both the c-wave and the SP oscillations were significantly reduced or absent. These findings indicate a primary photo-receptor disorder. Threshold studies for the scotopic b-wave showed a loss of retinal sensitivity early in the disease at a time when 30 Hz flicker responses were normal, which could indicate an earlier involvement of the rods than of the cones. There were no major alterations in the timing of the ERG in the affected animals tested. [ABSTRACT FROM PUBLISHER]

Necropsy material from the eye of a 23-year-old male known to have suffered from the Sjögren-Larsson syndrome, characterised by mental retardation, spastic diplegia or tetraplegia, congenital ichthyosis, and so-called glistening dots in the foveal and parafoveal areas of the fundus of the eye, was investigated ultrastructurally. The retinal pigment epithelium in the macular area showed a significant increase in lipofuscin granules, most likely because of a reduced capacity for digestion of phagocytosed material, and a significant decrease in melanin and melanolipofuscin granules in comparison with a normal control material. The ophthalmoscopically visible glistening dots and the pigment epithelial 'windows' seen on fluorescein angiography may possibly be explained by a further progression of these changes. No retinal changes were found in the macular area, the midperiphery, or the periphery that could be attributed with certainty to any other origin than post-mortem autolysis. More material would be needed, however, to elucidate further the fundal changes in the Sjögren-Larsson syndrome. [ABSTRACT FROM PUBLISHER]

A high water content lens (Scanlens 75, +14.5 dioptres) and a low water content lens (Bausch and Lomb Soflens H3, +14.5 dioptres) were compared with respect to corneal thickness response after 6 hours of wear in a provocative test on 12 aphakic eyes. The mean increase in central corneal thickness was 3.3% for Scanlens and 6.4% for Soflens. This difference is statistically highly significant (p less than 0.001). There seems to be a correlation between the response to Scanlens and that to Soflens when the responses of each eye were plotted against each other. Average lens thickness correlated somewhat better with corneal thickness increase than did central lens thickness. [ABSTRACT FROM PUBLISHER]

Purpose: To compare the performance and complication rates of PureVision (Bausch & Lomb, Inc.) high Dk/t silicone hydrogel lenses in 30-day continuous wear and 7-day extended wear., Methods: Five-hundred four (504) patients were randomized to 30-day continuous wear (353 patients) or to 7-day extended wear (151 patients) and followed for 12 months., Results: Eighty percent of patients did not report any symptoms/complaints at the follow-up exams. There were no cases of microbial keratitis. The annual incidence of the four most common clinically significant positive slit lamp findings related to lens wear for the 30-day and the 7-day groups, respectively, were as follows: corneal staining, 10.5% and 10.6%; corneal infiltrates, 4.6% and 2.3%; slight epithelial edema, 2.0% and 3.6%; and tarsal conjunctival abnormalities, 1.6% and 3.0%. There was no significant difference in complication rates between the groups. For reasons related to lens wear, 7.6% in the 30-day group and 13.2% in the 7-day group were dropped from the study. The patients' subjective judgment of comfort, visual quality, freedom from dryness, and lens handling varied from 89 to 95 on a scale of 0 to 100. The success rate was 82.9%, slightly better for the 30-day group (84.4%) than for the 7-day group (79.5%)., Conclusion: The complication rate was low. Sight-threatening events, such as bacterial keratitis did not occur. Inflammatory changes were seen, although at a low rate. Anterior segment changes related to hypoxia were minimal. Limbal and bulbar hyperemiadecreased significantly after switching patients to PureVision lenses. There was no significant difference in complication rates between the 30-day group and the 7-day group.

The RPE65 gene encodes a 65-kDa microsomal protein expressed exclusively in retinal pigment epithelium (RPE). Mutations in the human RPE65 gene have recently been identified in patients with autosomal recessive, severe, childhood-onset retinal dystrophy. Here we report the characterization of a 2.4-kb canine Rpe65 cDNA. The longest open reading frame predicts a 533-amino-acid protein with a calculated molecular mass of about 61 kDa prior to protein modification. Sequence comparison shows that RPE65 is highly conserved throughout mammalian evolution. We have identified a homozygous 4-bp deletion (485delAAGA) in putative exon 5 of the canine Rpe65 gene in affected animals of a highly inbred kinship of Swedish briard/briard-beagle dogs, in which an autosomal recessive, early-onset, and progressive retinal dystrophy segregates. The deletion results in a frameshift and leads to a premature stop codon after inclusion of 52 canine RPE65-unrelated amino acids from residue 153 onward. More than two-thirds of the wildtype polypeptide chain will be missing, and the mutant protein is most likely nonfunctional (null allele). Clinical features of the canine disease are quite similar to those described in human. Therefore this form of canine retinal dystrophy provides an attractive animal model of the corresponding human disorder with immediate significance for various therapeutic approaches, including RPE transplantation., (Copyright 1999 Academic Press.)

Purpose: Retinal pigment epithelial (RPE) cells slowly accumulate lipofuscin pigment within their acidic vacuolar apparatus as a result of extra- and/or intralysosomal oxidative alterations of phagocytosed photoreceptor outer segments (POS) with consequent imperfect degradation of these structures. In old age, lipofuscin accumulation may become quite substantial. It has been suggested that pronounced accumulation of lipofuscin is related to decreased RPE function and, possibly, to age-related macular degeneration. The aim of the present investigation was to study whether heavy loading with lipofuscin of RPE acidic lysosomes would affect the further phagocytic ability of the cells., Methods: In the first section of the investigation, cultures of rabbit RPE cells were exposed daily to bovine UV-irradiated POS (artificial lipofuscin) for 4 weeks, resulting in a pronounced lipofuscin accumulation of the cells. Fluorescent latex beads (labelled with a red fluorophore) were added to unloaded control cultures at O and 4 weeks after their establishment, and to lipofuscin loaded cells after 4 weeks of feeding with artificial lipofuscin. Cellular amounts of lipofuscin, and their phagocytotic activity, were quantified by static fluorometry measuring lipofuscin-specific and red bead-specific fluorescence, respectively. The intracellular location of the beads was verified by confocal laser scanning microscopy., Results: Unloaded, and thus almost lipofuscin-free, control cells exposed to latex beads showed numerous cytoplasmic particles emitting reddish fluorescence, while few particles were taken up by cells initially loaded with artificial, POS-derived, lipofuscin. Measurement of the latex bead-specific fluorescence showed significantly (p < 0.001) higher levels in unloaded control cells than in lipofuscin-loaded ones. In the second part of the investigation, unloaded control cultures and lipofuscin-loaded cultures were exposed to native bovine Texas Red-X-labelled POS 4 weeks after the establishment of the cultures. Unloaded control cells showed a large number of cytoplasmic POS emitting reddish fluorescence, while fewer POS were phagocytosed by cells loaded with artificial lipofuscin. Measurement of the Texas Red-X-specific fluorescence, thus quantifying the phagocytic ability of the cells, showed significantly (p < 0.001) higher levels in control cells than in lipofuscin-loaded ones., Conclusions: Severe lipofuscin accumulation of RPE cells appears to result in a greatly decreased phagocytic capacity. The resulting reduction in ability to cope with the needs of the overlying photoreceptor cells, in order to eliminate the obsolete tips of their POS, may well be of significance in the development of age-related macular degeneration.

Intracellular cyclic GMP concentration is known to change in response to a wide variety of agents, including hormones, neurotransmitters or light. In vertebrate photoreceptors, different membrane-bound guanylate cyclase isoforms are responsible for cGMP synthesis and thus directly involved in termination of light signalling via the phototransduction cascade and recovery of the dark state. We have characterized a 4.7 kb long cDNA for the canine retinal guanylate cyclase isoform E (cGC-E) predicting a polypeptide of 1109 amino acids. The genomic structure and the complete sequence of the canine GC-E gene, which consists of 20 exons and spans about 14.5 kb, has also been determined. Northern blot analysis showed that GC-E was expressed in the canine retina as a 4.7 and 6.1 kb large transcript. RT-PCR analysis also detected low expression in cerebrum (occipital lobe). We performed a sequence analysis of the cGC-E gene in animals of a Swedish Briard and Briard-Beagle dog kinship in which an inherited retinal dystrophy is segregating. Several intragenic DNA polymorphisms were identified and used for segregation analysis which excluded cGC-E as a candidate gene for this type of canine retinal dystrophy., (Copyright 1998 Elsevier Science B.V. All rights reserved.)

Purpose: Bacterial adherence or binding to the target cell is a prerequisite for the initial stage of most infections and seems to be mediated by lectin-like ligands on the bacterial surface and specific receptors on the target cell membrane. The purpose of this study was to establish whether contact lens wear under closed eye conditions changes the glycocalyx layer, whether it exposes more lectin receptors than eye closure without a contact lens, and whether wear of low oxygen transmissibility (Dk/L) contact lenses exposes more receptors than high Dk/L contact lenses., Methods: The eyes of six rabbits under general anesthesia were fit with either a high Dk/L soft contact lens (40 x 10(-9), boundary corrected) or a low Dk/L soft contact lens (2 x 10[-9]) or were left without a lens as controls. All eyes were kept closed by suturing for 24 hours. After removal of the contact lenses, all corneas were excised, put in glutaraldehydeforfixation, rinsed, incubated with plant-derived lectins (wheat-germ agglutinin [WGA]) conjugated with gold particles, and prepared for electron microscopy. Membrane associated gold particles were counted and the results were processed statistically., Results: After 24 hours of lens wear under closed eye conditions, the glycocalyx layer showed physical changes in the form of thinning or compression and signs of biochemical changes reflected as an increase in number of WGA receptors. The average number of membrane associated gold particles per 750 micro length of corneal epithelium in control corneas was 1,287.5 +/- 92.5. Particles were significantly (P<0.001) more numerous after wear of high Dk/L contact lenses (3,230.0 +/- 294.5) and after wear of low Dk/L contact lenses (4,611.3 +/- 223.3). The figure after wear of low Dk/L contact lenses was significantly (P<0.01) higher than the figure after wear of high Dk/L contact lenses., Conclusion: Our results indicate that lens wear under closed eye conditions seems to change the corneal glycocalyx layer physically as well as biochemically. Significantly larger numbers of WGA receptors were exposed after contact lens wear than without a contact lens. Significantly more receptors were exposed after wear of low Dk/L contact lenses than after wear of high Dk/L contact lenses. These changes may be of importance in relation to the risk of bacterial keratitis.

Purpose: Mutations of genes encoding various retina-specific proteins are known to cause a wide spectrum of inherited retinal dystrophies in different species. In the canine, several types of genetic retinal dystrophies have been described affecting primarily the photoreceptors and/or the retinal pigment epithelium. We are performing a systematic analysis of canine candidate genes for such diseases to identify the one mutated in the retinal dystrophy in Swedish Briard dogs., Methods: We isolated and characterised the full length cDNA of canine retinal arrestin by the method of rapid amplification of cDNA ends (RACE)., Results: The full length cDNA isolated by us is 1,575 base pairs (bp) long and contains a 1,218 bp-long open reading frame., Conclusions: The homology of the canine arrestin protein is highest with the human analogue (88.9%) and lowest with mouse arrestin (85.3%). The most obvious sequence differences among the different arrestins are in the extreme carboxyl terminus. PCR-SSCP (single strand conformation polymorphism) analysis and direct sequencing of retinal cDNA didn't provide any evidence that mutations in the canine arrestin gene are responsible for the retinal dystrophy seen in the Swedish strain of Briard dogs. Similar data were obtained for the genes encoding rhodopsin and the beta-subunit of photoreceptor-specific phosphodiesterase by segregation analysis.