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G M Gorrin

Publications and source records attributed to G M Gorrin.

9 recordsLinked to original sources
PubMed1999

Increased susceptibility to constant light in nr and pcd mice with inherited retinal degenerations.

PURPOSE: To determine whether the degenerating photoreceptors in nervous (nr/nr) and Purkinje cell degeneration (pcd/pcd) mutant mice are more susceptible to the damaging effects of constant light than those in age-matched normal mice. METHODS: Beginning at two ages for each mutant, albino nr/nr and pcd/pcd mice were placed into constant fluorescent light at an illuminance of 115 foot-candles to 130 foot-candles for a period of 1 week. Age-matched (usually littermate) normal (+/-) mice were exposed at the same time. The degree of photoreceptor cell loss was quantified histologically by obtaining a mean outer nuclear layer thickness for each animal. The light-exposed mice were compared with age-matched mutant and normal mice that were maintained in cyclic light. RESULTS: The homozygous mutants at each age showed a significantly greater loss of photoreceptor cells caused by constant light exposure than did the normal +/- mice in the same period of light exposure. The nr/nr and pcd/pcd mutants lost two to three times the number of photoreceptor cells than did the +/- mice during the constant light exposure. CONCLUSIONS: It has long been thought that excessive light may be harmful to patients with inherited or age-related photoreceptor degenerations. The present data add to other experimental evidence suggesting that photoreceptors already undergoing inherited or other forms of degeneration may be particularly susceptible to the damaging effects of excessive light.

Animals↗
PubMed1993

Retinal degeneration in the nervous mutant mouse. I. Light microscopic cytopathology and changes in the interphotoreceptor matrix.

Nervous is an autosomal recessive mutation in mice (gene symbol, nr) that produces a progressive cerebellar and retinal degeneration. We have examined various cytopathological features of the photoreceptor degeneration by light microscopy. An increase in the number of pyknotic photoreceptor nuclei in the outer nuclear layer (ONL) is first seen at postnatal day (P) 11. Between P13 and P19 there is a rapid loss of photoreceptors, with the ONL about 60% the thickness of littermate controls at P19. Between P19 and 2.5 months of age, photoreceptor cell loss is minimal, and there is a relatively slow loss of these cells between 3 and 7.5 months of age. At 7.5 months, the ONL consists of single row of nuclei, most of which are lost over the ensuing months, although a few photoreceptor nuclei persist at 17 months of age and older. Both rods and cones are lost at comparable rates for the first 2 months of life, but rods are somewhat preferentially lost at later ages. A very slight central-to-peripheral gradient of photoreceptor degeneration exists in the nr/nr retina, but no superior-inferior hemispheric differences are evident. The rate, spatiotemporal gradient, and hemispheric similarity in photoreceptor degeneration are the same in albino nr/nr mice reared either in cyclic light or in the dark, and in pigmented nr/nr mice. Autoradiographic analysis of rod outer segment renewal shows that outer segment membranes are synthesized in nervous homozygotes. Rhythmic outer segment disc shedding and phagocytosis by the retinal pigment epithelium occur at approximately normal rates in nr/nr mice. Histochemical and immunocytochemical study of the interphotoreceptor matrix (IPM) reveals the exclusion of stainable IPM from the outer segment zone by lamellar whorls of outer segment membrane, accumulation of stainable IPM in the basal region of the outer segment zone, and the absence of an intense band of stainable IPM at the apical surface of the retinal pigment epithelium. These changes in the IPM are similar to those seen in the Royal College of Surgeons rat. However, comparison of cytopathological changes in these two mutants reveal that the IPM defect probably is not the primary cause of photoreceptor cell death in nr/nr mice, and that similar phenotypic appearance does not necessarily signify similar pathological processes.

Animals↗
PubMed1993

Retinal degeneration in the nervous mutant mouse. II. Electron microscopic analysis.

Nervous mutant mice (nr/nr) show a rapid loss of most of cerebellar Purkinje cells between the ages of 3 and 7 weeks, as well as a progressive photoreceptor cell degeneration that occurs most rapidly between postnatal days (P) 13 and 19, but with a much slower attrition during the subsequent months. We have carried out an electron microscopic analysis of nr/nr and littermate control mice at representative ages to characterize the subcellular cytopathological changes in this form of retinal degeneration, to gain insight into photoreceptor cell degeneration mechanisms by comparing these changes to those in other rodent forms of retinal degeneration, and to compare the photoreceptor changes with those of cerebellar Purkinje cells. Ultrastructural observations were limited to rod photoreceptors, since the number of cones was limited in our micrographs. The retinas of nr/nr mutant mice can be distinguished from those of normal littermates as early as postnatal day (P) 6. At this time, some of the mitochondria in rod inner segments are larger and more rounded than normal. This represents the earliest cytopathological change thus far observed in this mutant. As early as P9 and thereafter, the volume and integrity of rod outer segment membranes are reduced from normal. In the inner segments of some rod photoreceptor cells, there is a reduction in the volume or number of polyribosomes as early as P11, a reduction in rough endoplasmic reticulum as early as P13, and reduced incidence and less organized Golgi membranes as early as P16. Qualitative evaluation and quantitative stereological analysis show that the enlarged mitochondria in rod inner segments never become normal in shape or size. No changes are seen in the inner retinal layers at any age. Despite similarities with inherited retinal dystrophy in the Royal College of Surgeons rat, as noted in the original description of retinal degeneration in nr/nr mice, ultrastructural features clearly distinguish these mutants. Moreover, nr/nr mice can be distinguished from all other murine forms of retinal degeneration by electron microscopy.

Animals↗
PubMed1987

Protection from light damage by ocular pigmentation: analysis using experimental chimeras and translocation mice.

Experimental mouse chimeras and Cattanach's translocation mice, both with alternating pigmented and non-pigmented cells of the retinal pigment epithelium (RPE), have been exposed to various periods of constant fluorescent light. Photoreceptor degeneration was always more severe in the central retina than in the peripheral retina, and it was independent of the pigmentation phenotype of the immediately overlying RPE. The findings suggest that although RPE melanosomes lower total retinal irradiance by absorption of light, they do not provide direct protection from light damage for the immediately underlying photoreceptor cells by a biochemical mechanism as previously suggested.

Animals↗
PubMed1987

Strain differences in sensitivity to light-induced photoreceptor degeneration in albino mice.

The sensitivity to light-induced photoreceptor degeneration was examined in 7 different inbred strains of albino mice. The mice were exposed to 3 weeks of constant fluorescent light at an illuminance level of 115-130 ft-c (ca. 1,265-1,430 lux), after which the eyes were examined histologically. The degree of light-induced photoreceptor degeneration was compared to that found in BALB/cByJ (BALB/c) albino mice, which have previously been described as sensitive to the damaging effects of light, and to C57BL/6J-c2J albino mice, which have been shown to be resistant to light-induced damage. Mice of the A/J, AKR/J and NZW/LacJ strains were indistinguishable from BALB/c mice in light sensitivity, as measured by mean outer nuclear layer thickness and the presence or absence of outer segment membranes. Mice of the Ma/MyJ and RF/J strains were somewhat more sensitive to light than BALB/c mice, and those of the RIIIs/J were far more sensitive than all of the other strains. The LG/J strain differed from other strains by individual mice displaying one of two degrees of light sensitivity, those similar to the light-sensitive Ma/MyJ and RF strains and those remarkably more resistant to light, with photoreceptor outer segment integrity even greater than that of the light-resistant C57BL/6J-c2J strain. These findings demonstrate that different inbred strains of a given species may exhibit a wide range of sensitivities to constant light exposure and that most albino mouse strains examined thus far are highly sensitive to the damaging effects of light.

Animals↗
PubMed1987

Genetic regulation of light damage to photoreceptors.

Albino mice of different inbred strains have been exposed to constant fluorescent lighting at an illuminance level of 115-130 ft-c for intervals of 1-6 weeks. Under these conditions the photoreceptors in retinas of albino BALB/cByJ mice rapidly degenerate, whereas the photoreceptors in retinas of albino C57BL/6J-c2J mice are remarkably more resistant to light damage. F1 heterozygotes produced from these two strains display an intermediate degree of light-induced degeneration. These findings demonstrate that phenotypically identical populations with different genetic constitutions can show markedly different sensitivities to light, and that genetic factors must now be included as a determinant for the severity of light damage.

Animals↗
PubMed1978

Localization of lysosomal enzymes in retinal pigment epithelium of rats with inherited retinal dystrophy.

Four acid hydrolase activities are demonstrable by light microscopy in pigment epithelial cell lysosomes of rats (Royal College of Surgeons--RCS) with inherited retinal dystrophy and in control (Fischer) rats. The enzymes include acid phosphatase, aryl sulfatase, N-acetyl-beta-glucosaminidase, and esterase activities. No marked differences are observed in distribution or staining intensity of lysosomes in the two strains of rat. Acid hydrolase activities are not localized in sites other than lysosomes. Acid phosphatase and aryl sulfatase activities are also demonstrable by electron microscopy. In both strains, acid phosphatase reaction product is localized to various forms of lysosomes in pigment epithelial cells. A diffuse precipitate, considered to be nonspecific in origin, is seen in the cytoplasm, apical processes, outer segments (control), and outer segment debris (RCS). The precipitate is probably due to adsorption of lead from the incubation medium or of lead phosphate that diffuses from heavy accumulations in nearby lysosomes. Aryl sulfatase reaction product, in contrast to acid phosphatase, is localized to far fewer lysosomes and there is virtually no nonspecific precipitate. The findings indicate that lysosomes of RCS pigment epithelial cells possess several cytochemically demonstrable acid hydrolase activities. There is no evidence for the localization of acid phosphatase (or aryl sulfatase) activities in sites other than lysosomes.

Acid Phosphatase↗