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At least 721 records · Page 40Linked to original sources

PubMed2000

Early postnatal Müller cell death leads to retinal but not optic nerve degeneration in NSE-Hu-Bcl-2 transgenic mice.

Topographically localized over-expression of the human Bcl-2 protein in retinal glial Müller cells of a transgenic mice (line 71) leads to early postnatal apoptotic Müller cell death and retinal degeneration. Morphological, immunohistological and confocal laser microscopic examination of transgenic and wild-type retinas were achieved on paraffin retinal sections, postnatally. Apoptosis occurs two to three days earlier in the internal nuclear layer of transgenic retinae, than in wild-type littermates. In parallel there was a progressive disappearance of transgenic Hu-Bcl-2 over-expression, as well as of the Müller cell markers, cellular retinaldehyde-binding protein and glutamine synthetase. This phenomenon led to retinal dysplasia, photoreceptor apoptosis and then retinal degeneration and proliferation of the retinal pigment epithelium. The optic nerve, however, remains intact. Two complementary observations confirm the pro-apoptotic action of Bcl-2 over-expression in Müller cells: (i) in the peri-papillary and peripheral regions where the transgene Bcl-2 is not expressed, cellular retinaldehyde-binding protein or glutamine synthetase immunostaining persist and Müller glia do not die; and (ii) the retina conserves a normal organisation in these two regions in spite of total retinal degeneration elsewhere. We conclude that retinal dysplasia and degeneration are linked to primary Müller cell disruption. Besides its generally accepted anti-apoptotic function, over-expression of Bcl-2 also exerts a pro-apoptotic action, at least in immature Müller glia. One may suppose that Bcl-2 translocation resulting in its over-expression in retinal Müller cells could be a putative mechanism for early retinal degeneration.

Aging↗

PubMed1982

Peripheral nerve phospholipid composition: development in normal nerve and age-dependent changes in Wallerian degenerated nerve.

The phospholipid composition of normal peripheral nerve as a function of developmental age as well as that of Wallerian-degenerated nerve as a function of age at nerve transection and duration of Wallerian degeneration have been quantitated in rabbit sciatic nerve. During development, increases in the proportions of ethanolamine plasmalogen, sphingomyelin, and combined phosphatidyl serine plus phosphatidyl inositol and decreases in the proportions of phosphatidyl choline and phosphatidyl ethanolamine correlated well with the concurrent myelin accretion. During Wallerian degeneration, age-dependent changes in phospholipid composition were observed. The large and statistically significant increase in the proportion of phosphatidyl choline and decrease in the proportion of ethanolamine plasmalogen were manifest promptly in nerves transected at 2 weeks of age but in a delayed manner in nerves transected at 8, 12, and 20 weeks of age. The rate of loss of individual phospholipids was greater in nerves transected at younger ages. The findings from normal developing peripheral nerve may well serve as baseline data for subsequent studies of phospholipid composition in pathological peripheral nerve. The findings from Wallerian-degenerated peripheral nerve provide additional evidence for age-dependent chemical changes occurring in Wallerian-degenerated peripheral nerve that may be of significance in explaining the superior functional recovery from peripheral nerve injury observed in younger compared with older subjects.

Aging↗

PubMed1980

A family with vitreo-tapeto-retino-choroidal degeneration with dominant transmission.

A family with vitreo-tapeto-retino-choroidal degeneration is presented. Five members of a sibship of nine and their mother are affected. Retinal changes in the form of macular degeneration and peripheral preretinal membranes are the most prominent features. Other manifestations are vitreous degeneration, optic atrophy, equatorial pigmentation, and complicated cataract. The heredity is probably autosomal dominant. Comparisons are made with the well-known hereditary vitreo-retinal degenerations, in particular with Wagner's disease. Above all, the extensive macular degeneration in two of the patients, involving the retina, the pigment epithelium, and the choriocapillaris, distinguishes the present disorder from the above-mentioned.

Adolescent↗

PubMed1983

Wallerian degeneration of the corticospinal tract region of the brain stem: demonstration by computed tomography.

Pathophysiological and CT aspects of wallerian degeneration of the corticospinal tract in the brain stem were studied in patients with old hemispheric infarcts. There was found to be a clear relationship between (a) the location and size of the infarcts and (b) the presence or absence of wallerian degeneration. When most of the motor cortex is involved, degeneration can be seen at least as far as the mesencephalic level and sometimes down to the pontine level. Isolated capsular infarcts which spare the motor cortex are also associated with degeneration. No degeneration could be seen in patients with small infarcts.

Aged↗

PubMed1976

[Goldmann-Favre hyaloido-tapetoretinal degeneration].

In a sister and brother we found a case of vitreo-tapeto-retinal degeneration (macular retinoschisis, night-blindness, vitreous micro-fibrillose degeneration, abolished E.R.G., very pathological E.O.G.) and a "fruste" form of tapeto-retinal degeneration (De Lange's curve and flicker-E.R.G. both modified, E.R.G. subnormal and slight pathological changes in adaptometry). The father of these two patients suffered from tapeto-retinal degeneration which had caused complete blindness. Basing their suppositions on their personal experience and medical literature, the authors believe that the type of vitreo-retinal degeneration is best determined after examination of the mode of hereditary transmission. In the family which is presented, they believe that it is a form of Goldmann-Favre's disease with pseudo-dominance.

Adaptation, Ocular↗

PubMed1984

The non-directional pattern of axonal changes in Wallerian degeneration: a computer-aided morphometric analysis.

Wallerian degeneration was investigated to determine whether axonal changes occur progressively in a somatofugal or somatopetal direction or simultaneously along the length of the axon. Microtubule density was used as a measure of the extent of axonal degeneration and was assessed by a computer-aided analysis of electron micrographs. The left sural nerves of ten rats were crushed and 30 hours later axonal areas and axonal microtubule numbers were recorded from a large sample of axons at two sites 1 cm and 3 cm distal to the crush. The same recordings were made from the right unoperated nerve at two comparable sites. Statistical analysis of all the data provided no evidence for a somatofugal or reverse direction of degeneration. It is concluded therefore that in Wallerian degeneration axonal changes, as indicated by microtubule dissolution, occur simultaneously along the length of the axon. It is proposed that to interpret the conflicting published data on the direction of fibre degeneration, Schwann cell changes (e.g. myelin ovoid formation) and axonal changes (e.g. microtubule dissolution) should be considered independently since they have different aetiological mechanisms which may account for the differing experimental results reported.

Animals↗

PubMed1981

[Different manifestations of tapetoretinal degeneration in the same family (author's transl)].

A family with two siblings with six cases of tapetoretinal degeneration is reported. In the first case one individual present a degeneration of both scotopic and photopic visual systems, whereas another patient had macular degeneration of the Stargardt type. In the second, there was one case of photopic and stotopic degeneration, one case of fundus flavimaculatus, one case of Stargardt disease, and one case of retinitis pigmentosa inversa. The study of this family suggests on the one hand that Stargardt disease and fundus flavimaculatus are expressions of the same disease. On the other hand, the simultaneous presence of central and diffuse alterations of the fundus raises the question as to whether these various forms of hereditary degeneration may be included in a single class of disease.

Adolescent↗

PubMed2006

Clinically undetected motor neuron disease in pathologically proven frontotemporal lobar degeneration with motor neuron disease.

BACKGROUND: Frontotemporal lobar degeneration with motor neuron disease (FTLD-MND) is a pathological entity characterized by motor neuron degeneration and frontotemporal lobar degeneration. The ability to detect the clinical signs of dementia and motor neuron disease in pathologically confirmed FTLD-MND has not been assessed. OBJECTIVES: To determine if all cases of pathologically confirmed FTLD-MND have clinical evidence of frontotemporal dementia and motor neuron disease, and to determine the possible reasons for misdiagnosis. METHOD: Review of historical records and semiquantitative analysis of the motor and extramotor pathological findings of all cases of pathologically confirmed FTLD-MND. RESULTS: From a total of 17 cases of pathologically confirmed FTLD-MND, all had clinical evidence of frontotemporal dementia, while only 10 (59%) had clinical evidence of motor neuron disease. Semiquantitative analysis of motor and extramotor pathological findings revealed a spectrum of pathological changes underlying FTLD-MND. Hippocampal sclerosis, predominantly of the subiculum, was a significantly more frequent occurrence in the cases without clinical evidence of motor neuron disease (P<.01). In addition, neuronal loss, gliosis, and corticospinal tract degeneration were less severe in the other 3 cases without clinical evidence of motor neuron disease. CONCLUSIONS: Clinical diagnostic sensitivity for the elements of FTLD-MND is modest and may be affected by the fact that FTLD-MND represents a spectrum of pathological findings, rather than a single homogeneous entity. Detection of signs of clinical motor neuron disease is also difficult when motor neuron degeneration is mild and in patients with hippocampal sclerosis.

Adult↗

PubMed1996

Genetic influences on cellular reactions to spinal cord injury: a wound-healing response present in normal mice is impaired in mice carrying a mutation (WldS) that causes delayed Wallerian degeneration.

Progressive tissue necrosis is a process unique to the injured mammalian spinal cord which often leads to gradually increasing cavitation and enlargement of the lesion. To evaluate the role of neuronal degeneration in initiating this response, histopathological changes were compared in C57BL and WldS (delayed Wallerian degeneration mutation) mice. The spinal cord was crushed at T8, producing a primary lesion at the site of the trauma and a secondary lesion extending rostrocaudally in the dorsal columns (where long ascending and descending fiber tracts undergo Wallerian degeneration). Cavitation was relatively mild at both sites and developed mainly at the margins of the lesions. In striking contrast to spinal cord injury in rats, progressive necrosis did not occur in mice; instead, the primary and secondary lesion sites became filled in by macrophages and fibroblasts embedded in a well-vascularized collagenous stroma. Quantitative image analysis revealed that the primary lesion decreased dramatically in size and cavitation between 2 and 3 weeks in C57BL, whereas in WldS the reduction in size and cavitation began later (at 4 weeks) and was less complete. The initial development of the secondary lesion began later and its healing was less complete in WldS than C57BL. These results are consistent with the hypothesis that neuronal damage, including Wallerian degeneration, triggers inflammatory responses leading to tissue repair. For this reason, any delay in neuronal degeneration, as in the WldS mutation, results in deficient tissue repair as reflected in the larger size of both primary and dorsal column lesions.

Animals↗

PubMed1998

Neuronal degeneration in the gerbil brainstem is associated with spongiform lesions.

Spongiform lesions arise in dendrites and glia in the brainstem of domestic Mongolian gerbils. Most pronounced within the cochlear nucleus (CN), this disorder is dynamic and progressive; the lesions increase in number, size, and extent with age. It has not been clear whether these spongioid lesions either cause or are associated with significant neural degeneration. In contrast, feral Mongolian gerbils (wild-trapped in Tuva) and their offspring show few spongiform lesions. The Tuvan gerbils provide an appropriate within-species control. We compared degeneration in the brainstem of domestic and Tuvan gerbils using the amino-cupric-silver (ACS) stain of de Olmos et al. [(1994) Neurotoxicol. Teratol., 16:545-561]. Positive histologic controls were provided by cerebellar stab wounds in domestic gerbils and by unilateral kainic acid injections into the CN of Tuvan gerbils. The ACS stain revealed extensive degeneration of axons, terminals, dendrites, and neurons in the brainstem of domestic gerbils. Neurodegeneration was most pronounced in the CN and was coextensive with spongiform lesions. Neurodegeneration was also seen in the trapezoid body, lateral lemniscus, and inferior colliculus, but was less pronounced than in the CN. The cerebellar stab wounds resulted in silver-stained Purkinje cells restricted to the stab wound local region. Kainic acid produced extensive neuronal and spongiform degeneration of the injected CN that was very similar to that spontaneously occurring in domestic gerbils. In contrast, the non-injected CN of Tuvan gerbils showed no neuronal or spongiform degeneration with the ACS stain. We conclude that, in domestic gerbils, the naturally occurring spongiform lesions of the CN and the accompanying neurodegeneration are both results of a common mechanism, most probably excitotoxic.

Animals↗

PubMed2000

Retinal degeneration in licensed pesticide applicators.

BACKGROUND: Retinal degeneration is the leading cause of visual impairment in older adults, but little is known about its relationship to neurotoxic exposures. METHODS: The Agricultural Health Study is a cohort study of licensed pesticide applicators from Iowa and North Carolina. We used cross-sectional data from self-administered questionnaires given at enrollment in 1994-1996 to compare pesticide use in 154 applicators who reported retinal degeneration and 17,804 controls. RESULTS: Retinal degeneration was associated with fungicide use (odds ratio = 1.8, 95% confidence interval = 1.3-2.6). This relationship was seen in subgroups defined by state, demographic characteristics, or medical history, as well as in the entire group. Risk increased with cumulative days of fungicide use (P for trend = 0.011) and was greater when application methods involving greater personal exposure were used. Retinal degeneration was also related to use of organochlorine or carbamate insecticides, but these associations were less consistent. Since nearly all applicators used organophosphate insecticides and herbicides, these exposures could not be effectively evaluated. CONCLUSIONS: These results suggest that exposure to some fungicides and insecticides may increase risk of retinal degeneration.

Adolescent↗

PubMed2000

Antioxidant vitamin and mineral supplementation for preventing age-related macular degeneration.

BACKGROUND: Some observational studies have suggested that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration. OBJECTIVES: The aim of this review is to examine the evidence as to whether or not taking vitamin or mineral supplements prevents the development of age-related macular degeneration. SEARCH STRATEGY: We searched the Cochrane Eyes and Vision Group specialised register, the Cochrane Controlled Trials Register - Central, MEDLINE, reference lists of identified reports and the Science Citation Index. We contacted investigators and experts in the field for details of unpublished studies. The most recent searches were conducted in June 1999. SELECTION CRITERIA: All randomised trials comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control were included. We included only studies where supplementation had been given for at least one year. DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trial quality. Currently there is only one published trial included in the review so no data synthesis was conducted. MAIN RESULTS: One trial is included in the review. This was a primary prevention trial in Finnish male smokers with four treatment groups: alpha-tocopherol alone, beta-carotene alone, alpha-tocopherol and beta-carotene, placebo. The add-on maculopathy study was conducted in a subset of the main trial cohort. 269 cases of maculopathy (14 late stage age-related macular degeneration) were identified. There was no association of age-related macular degeneration with treatment. REVIEWER'S CONCLUSIONS: There is no evidence to date that people without age-related macular degeneration should take antioxidant vitamin and mineral supplements to prevent or delay the onset of the disease. The results of five large ongoing trials are awaited.

Antioxidants↗

PubMed2000

Ginkgo biloba extract for age-related macular degeneration.

BACKGROUND: Ginkgo is used in the treatment of peripheral vascular disease and 'cerebral insufficiency'. It is thought to have several potential mechanisms of action including increased blood flow, platelet activating factor antagonism and prevention of membrane damage caused by free radicals. Vascular factors and oxidative damage are thought to be two potential mechanisms in the pathology of age-related macular degeneration. OBJECTIVES: The objective of this review is to determine the effect of Ginkgo biloba extract on the progression of age-related macular degeneration. SEARCH STRATEGY: The Cochrane Eyes and Vision Group specialised register, the Cochrane Controlled Trials Register - Central, MEDLINE, reference lists of identified trial reports, and the Science Citation Index were searched. The reviewer contacted Investigators of included studies for additional information. The most recent searches were performed in February 2000. SELECTION CRITERIA: All randomised trials where Ginkgo biloba extract had been compared to control in people with age-related macular degeneration were included. DATA COLLECTION AND ANALYSIS: The reviewer extracted data using a standardised form. The data were verified with the trial investigator. MAIN RESULTS: One published trial was identified. Although a beneficial effect was observed, as only 20 people were enrolled in the trial, and assessment of outcome was not masked, its results must be considered equivocal. Adverse effects and quality of life for people with age-related macular degeneration have not been addressed. One unpublished trial is awaiting translation and assessment. REVIEWER'S CONCLUSIONS: The question as to whether people with age-related macular degeneration should take Ginkgo biloba extract to prevent progression of the disease has not been answered by research to date.

Ginkgo biloba↗

PubMed2004

A novel endogenous erythropoietin mediated pathway prevents axonal degeneration.

Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate that the relevant axonal injury signal that stimulates EPO production from surrounding glial cells is nitric oxide. In addition, we show that this endogenous pathway can be therapeutically exploited by administering exogenous EPO. In an animal model of distal axonopathy, systemic EPO administration prevents axonal degeneration, and this is associated with a reduction in limb weakness and neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO prevents axonal degeneration and therefore may be therapeutically useful in a wide variety of human neurological diseases characterized by axonopathy.

Animals↗

PubMed2002

Mast cells in Wallerian degeneration: morphologic and ultrastructural changes.

The morphologic and ultrastructural changes of mast cells were followed in degenerating distal and regenerating proximal stumps of frog brachial nerve during Wallerian degeneration. Quantitative analysis included determination of both number and size of mast cells. The mast cell response to injury consisted of an early and a late phase. In the early phase, there was an increase in mast cell numbers in the proximal site of the lesion and a release of Alcian blue material consistent with mediator release. This phase of mast cell activation may be related, through the secretion of biogenic agents such as heparin and histamine, to the increase of endoneurial vessel size and vascular permeability, providing access for macrophages and mast cell precursors. The later phase, which peaked at 40 days after transection in the degenerating distal stump, consisted in the degranulation of the mast cells. These mast cells, closely associated with macrophages and degenerating Schwann cells, released secretory granules into the endoneurial microenvironment. These degranulating mast cells, through the released acid hydrolases, may contribute along with macrophages and Schwann cells, to the degradation of myelin debris. At the same time, mast cells appeared filled with granular content in the regenerating proximal segment. Therefore, we suggest that mast cells in peripheral nerves may play an important role in nerve degenerating and regenerating mechanisms through the secretion of diffusible molecules.

Animals↗

PubMed2007

Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: a morphological and ERG study.

Retinal degeneration 10 (rd10) mice are a model of autosomal recessive retinitis pigmentosa (RP), identified by Chang et al. in 2002 (Vision Res. 42:517-525). These mice carry a spontaneous mutation of the rod-phosphodiesterase (PDE) gene, leading to a rod degeneration that starts around P18. Later, cones are also lost. Because photoreceptor degeneration does not overlap with retinal development, and light responses can be recorded for about a month after birth, rd10 mice mimic typical human RP more closely than the well-known rd1 mutants. The aim of this study is to provide a comprehensive analysis of the morphology and function of the rd10 mouse retina during the period of maximum photoreceptor degeneration, thus contributing useful data for exploiting this novel model to study RP. We analyzed the morphology and survival of retinal cells in rd10 mice of various ages with quantitative immunocytochemistry and confocal microscopy; we also studied retinal function with the electroretinogram (ERG), recorded between P18 and P30. We found that photoreceptor death (peaking around P25) is accompanied and followed by dendritic retraction in bipolar and horizontal cells, which eventually undergo secondary degeneration. ERG reveals alterations in the physiology of the inner retina as early as P18 (before any obvious morphological change of inner neurons) and yet consistently with a reduced band amplification by bipolar cells. Thus, changes in the rd10 retina are very similar to what was previously found in rd1 mutants. However, an overall slower decay of retinal structure and function predicts that rd10 mice might become excellent models for rescue approaches.

Animals↗

PubMed1978

Temporal and spatial sequence of anterograde degeneration in the cochlear nerve fibers of the cat. A light microscopic study.

This study deals with anterograde degeneration in the cochlear nerve fibers following cochlear lesions. The observations are based on 2-mum thick sections of material embedded in resin according to procedures used in electron microscopy and stained with toluidine blue. Among the various operative approaches used in this study, sparing of the modiolus afforded the least local reaction and furnished the material best suited for anterograde degneration studies in this nerve only 2 mm long. The anterograde degeneration of the cochlear nerve is characterized by segmental swelling of myelinated nerve fibers followed by shrinkage of the axoplasm and collapse of the distended myelin sheaths. The swelling, which begins at the nodal-paranodal region of the axon, is preceded by accumulation in the cytoplasm of granular organelles, presumably mitochondria and lysosomes. The portions of the cochlear fibers situated in the nerve root, i.e., within the cochlear nuclei and including the axon terminals, follow essentially the same pattern of degeneration as those in the peripheral portion of the nerve. Both peripherally and centrally degenerative changes occur first in the basal, high frequency fibers and centrally degenerative changes occur first in the basal, high frequency fibers and progress to the apical, low frequency fibers. The difference between the two extremes in the onset of degeneration is, approximately, 24 hours. Once initiated, however, the pace of degeneration is the same along the whole fiber spectrum.

Animals↗

PubMed1982

Retinal degeneration in the pcd cerebellar mutant mouse. I. Light microscopic and autoradiographic analysis.

The Purkinje cell degeneration (pcd) mutant mouse rapidly loses cerebellar Purkinje cells between 3 and 5 weeks after birth and slowly loses retinal photoreceptor cells during the first year of life. In the present study, the retinal degeneration in the pcd mouse was analyzed by light microscopy and autoradiography throughout the first 15 months of age. By day 25 there is an abundance of pyknotic photoreceptor nuclei and many outer segments are clearly disorganized. Thereafter, as the photoreceptor cells are lost, their outer segments slowly become shorter and more variable in length; this slow change in length is explained by an almost proportional reduction in both rod outer segment renewal and disc shedding rates. At about 2 months of age, the rate of rod outer segment renewal is slightly less than half that in littermate controls, and the number of large phagosomes in pigment epithelial cells during the burst of disc shedding soon after light onset is one-half or less than that seen in littermate controls. Between 2 and 10.5 months of age, the retina in the inferior hemisphere of the eye shows substantially more-advanced photoreceptor degeneration than does the superior hemisphere, particularly in the far peripheral retina. A central-to-peripheral gradient of degeneration is conspicuous in the superior hemisphere; a similar but less obvious gradient of degeneration is also seen in the inferior hemisphere of the eye. Loss of photoreceptor cells and their synaptic terminals results in a predictable thinning of the outer synaptic layer. However, the inner nuclear layer shows no measurable thinning and the inner synaptic layer is reduced in thickness by only about 5-15%. Beginning at about 10 months of age, foci of thinned pigment epithelial cells are evident, and by 12 months there is some vascularization of the pigment epithelium by retinal capillaries.

Animals↗