1.Spinocerebellar Ataxia Type 7 without Retinal Degeneration: A Case Rreport.
Byeong Chae KIM ; Myeong Kyu KIM ; Ki Hyun CHO ; Beom S JEON
Journal of Korean Medical Science 2002;17(4):577-579
A 60-yr-old man developed progressive gait disturbance and limb ataxia at the age of 52. Family history was absent for neurological disorders. Examinations showed pure cerebellar syndrome. There was no retinal degeneration for 7 yr. A brain MRI done at the age of 56 showed atrophy of the cerebellar hemispheres and vermis. Genetic test confirmed the spinocerebellar ataxia type 7 with CAG repeat number of 42.
Brain/pathology
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Humans
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Korea
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Magnetic Resonance Imaging
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Male
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Middle Aged
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Retinal Degeneration/genetics/*pathology
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Spinocerebellar Ataxias/genetics/*pathology
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Trinucleotide Repeat Expansion
2.Morphologic studies of the retina in a new diabetic model; SHR/N:Mcc-cp rat.
Soon Hyun KIM ; Young Kwang CHU ; Oh Woong KWON ; Sylvia A MCCUNE ; Frederick H DAVIDORF
Yonsei Medical Journal 1998;39(5):453-462
The pathogenesis of diabetic retinopathy has not been fully explained. The earliest histological lesion is the loss of intramural pericytes and thickening of the basement membrane. Increased activity of the polyol pathway is a probable mechanism for these two abnormalities. Investigations have suffered from the lack of an exact animal model simulating the human condition. Examination of the retina in the spontaneously diabetic SHR/N:Mcc-cp rat demonstrated degeneration and loss of intramural pericytes, a progressive increase in basement membrane thickness, and microinfarctions with an area of non-perfusion. Therefore, this model may be used to clarify the biochemical mechanisms linking the metabolic abnormalities of diabetes and retinopathy.
Animal
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Diabetic Retinopathy/pathology*
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Disease Models, Animal
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Female
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Hybridization
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Male
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Rats
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Rats, Inbred SHR/genetics
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Rats, Inbred Strains/genetics
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Retina/pathology*
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Retinal Degeneration/pathology
3.Effect of Heat Shock Protein 72 Expression on Etoposide-induced Cell Death of Rat Retinal Ganglion Cells.
Seongsoo SOHN ; Ji Eun IM ; Tae Eun KIM ; Changwon KEE
Korean Journal of Ophthalmology 2013;27(1):48-51
PURPOSE: To assess whether the expression of heat shock protein 72 (Hsp72) protects rat retinal ganglion cells (RGC-5) from apoptotic cell death. METHODS: Hsp72 expression in RGC-5 cells transduced with replication-deficient recombinant adenovirus was analyzed by Western blot analysis and immunofluorescence. The effect of Hsp72 expression on etoposide-induced apoptotic cell death was examined by microscopic analysis and confirmed by cell proliferation assay. RESULTS: Western blot analysis and immunofluorescence clearly showed adenovirus-mediated Hsp72 expression in RGC-5 cells. Treatment with etoposide resulted in the death of a proportion of the cells by apoptosis. However, this apoptotic cell death was significantly reduced in cells expressing Hsp72, with the reduction in cell death correlating to the level of Hsp72 expression. CONCLUSIONS: Over-expression of Hsp72 alone is sufficient to rescue neuronal cells from apoptotic cell death, suggesting that fine-tuning its expression may be an effective neuroprotective approach in retinal degenerative disease.
Animals
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Blotting, Western
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Cell Death/*genetics
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Cell Survival
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Cells, Cultured
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DNA/*genetics
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Disease Models, Animal
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Etoposide/toxicity
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*Gene Expression Regulation
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HSP72 Heat-Shock Proteins/biosynthesis/*genetics
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Immunohistochemistry
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Rats
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Retinal Degeneration/*genetics/metabolism/pathology
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Retinal Ganglion Cells/drug effects/*metabolism/pathology
4.Effect of the absence of heat shock protein 70.1 (hsp70.1) on retinal photoreceptors in normal and rd mice.
Young Suk YU ; Jun Ho HEO ; Sang Won HWANG ; Jeong Hun KIM ; Jeong Sun SEO ; Sang In KHWARG ; Hum CHUNG
Korean Journal of Ophthalmology 2001;15(2):67-73
The purposes of this study are to elucidate the retinal changes of heat shock protein 70.1 (hsp70.1) knockout mice and to compare them between in normal and in retinal degeneration (rd) mice. Eyes of hsp70.1 wild type (+/+) and knockout (-/-) mice in the C57BL/6 or FVB genetic backgrounds respectively, which were reared in the normal environment, were examined by fundus photography, electroretinography, light microscopy, terminal dUTP nick-end labeling (TUNEL) stain, and immunohistochemistry. In C57BL/6 mice, fundus photography showed no changes between hsp70.1+/+ and -/- mice at 1 and 6 months of age. Electroretinographic examination showed a tendency of decreased amplitude of a- and b-wave with aging in both genotype, but there were not different statistically. The ratios of the thickness of inner nuclear and outer nuclear layer to the retinal thickness were respectively decreased with aging in both genotype, but there were not different statstically. TUNEL assay showed a few positively labeled cells in the ganglion cell, inner nuclear and outer nuclear layers and the immunohistochemistry showed no immunopositivity of hsp70 in the inner segments of photoreceptor cell layer in both genotype. In rd mice, fundus photography showed a narrowing of the retinal vessels at the age of 4 weeks, however, there were no differences of retinal changes including pigment epithelial layer in both genotype. Electroretinographic examination at the postnatal 2, 3 and 4 weeks showed no differences between them. Loss of photoreceptor cell and outer nuclear layers showed no differences in both genotype. In conclusion, there were no differences of the retinal changes at least under the normal environmental condition in hsp70.1+/+ and -/- mice. These results show that hsp70.1-/- mice can be used to study the role of hsp70.1 to the external stress to the retina.
Animal
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Electroretinography
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Fundus Oculi
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Heat-Shock Proteins 70/*deficiency/genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout/genetics
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Photoreceptors, Vertebrate/*metabolism
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Protozoan Proteins/genetics
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Reference Values
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Retinal Degeneration/metabolism/*pathology/*physiopathology
5.Expression of human FUS protein in Drosophila leads to progressive neurodegeneration.
Yanbo CHEN ; Mengxue YANG ; Jianwen DENG ; Xiaoping CHEN ; Ye YE ; Li ZHU ; Jianghong LIU ; Haihong YE ; Yan SHEN ; Yan LI ; Elizabeth J RAO ; Kazuo FUSHIMI ; Xiaohong ZHOU ; Eileen H BIGIO ; Marsel MESULAM ; Qi XU ; Jane Y WU
Protein & Cell 2011;2(6):477-486
Mutations in the Fused in sarcoma/Translated in liposarcoma gene (FUS/TLS, FUS) have been identified among patients with amyotrophic lateral sclerosis (ALS). FUS protein aggregation is a major pathological hallmark of FUS proteinopathy, a group of neurodegenerative diseases characterized by FUS-immunoreactive inclusion bodies. We prepared transgenic Drosophila expressing either the wild type (Wt) or ALS-mutant human FUS protein (hFUS) using the UAS-Gal4 system. When expressing Wt, R524S or P525L mutant FUS in photoreceptors, mushroom bodies (MBs) or motor neurons (MNs), transgenic flies show age-dependent progressive neural damages, including axonal loss in MB neurons, morphological changes and functional impairment in MNs. The transgenic flies expressing the hFUS gene recapitulate key features of FUS proteinopathy, representing the first stable animal model for this group of devastating diseases.
Aged
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Aging
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genetics
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metabolism
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pathology
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Amyotrophic Lateral Sclerosis
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genetics
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metabolism
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pathology
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Animals
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Animals, Genetically Modified
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Disease Models, Animal
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Drosophila melanogaster
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genetics
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metabolism
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Gene Expression
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Humans
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Microscopy, Electron, Scanning
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Motor Neurons
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metabolism
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pathology
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Mushroom Bodies
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metabolism
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pathology
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Mutant Proteins
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genetics
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metabolism
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Mutation
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Photoreceptor Cells, Invertebrate
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metabolism
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pathology
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Plasmids
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RNA-Binding Protein FUS
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genetics
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metabolism
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Recombinant Fusion Proteins
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genetics
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metabolism
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Retinal Degeneration
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pathology
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physiopathology
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Transfection
6.Ophthalmologic Findings of Boucher-Neuhauser Syndrome.
Sun Im YU ; Jung Lim KIM ; Sul Gee LEE ; Hyun Woong KIM ; Sang Jin KIM
Korean Journal of Ophthalmology 2008;22(4):263-267
To report a case of Boucher-Neuhauser syndrome, which is an autosomal recessive disorder characterized by the triad of spinocerebellar ataxia, chorioretinal dystrophy, and hypogonadotropic hypogonadism. An 18-year-old man was seen for visual problems, which had been diagnosed as retinitis pigmentosa at the age of 12 years. His puberty was delayed. At 16 years of age, the patient experienced progressive deterioration of his balance and gait disturbance. Then he was referred to our clinic because Boucher-Neuhauser syndrome was suspected. He had no specific family history; his visual acuity was 0.04 in both eyes. We observed broad retinal pigment epithelium atrophy and degeneration in both fundi. Both fluorescein and indocyanine green angiography showed choriocapillaris atrophy in the posterior pole area and midperiphery. Macular optical coherence tomography showed thinning of the neurosensory retina. An electroretinographic examination showed no photopic or scotopic responses. The Boucher-Neuhauser syndrome should be included in the differential diagnosis of patients with retinitis pigment epithelium atrophy and degeneration.
Adolescent
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Atrophy
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Cerebellum/pathology
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Coloring Agents/diagnostic use
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Electroretinography
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Fluorescein Angiography
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Humans
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Hypogonadism/*diagnosis/genetics
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Indocyanine Green/diagnostic use
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Magnetic Resonance Imaging
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Male
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Photoreceptor Cells, Vertebrate/physiology
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Retinal Degeneration/*diagnosis/genetics
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Retinal Pigment Epithelium/*pathology
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Retinitis Pigmentosa/*diagnosis/genetics/physiopathology
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Spinocerebellar Degenerations/*diagnosis/genetics
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Syndrome
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Tomography, Optical Coherence
7.Gene expression profiling of light-induced retinal degeneration in phototransduction gene knockout mice.
Jayalakshmi KRISHNAN ; Jiayan CHEN ; Kum Joo SHIN ; Jong Ik HWANG ; Sang Uk HAN ; Gwang LEE ; Sangdun CHOI
Experimental & Molecular Medicine 2008;40(5):495-504
Exposure to light can induce photoreceptor cell death and exacerbate retinal degeneration. In this study, mice with genetic knockout of several genes, including rhodopsin kinase (Rhok-/-), arrestin (Sag-/-), transducin (Gnat1-/-), c-Fos (c-Fos-/-) and arrestin/transducin (Sag-/-/Gnat1-/-), were examined. We measured the expression levels of thousands of genes in order to investigate their roles in phototransduction signaling in light-induced retinal degeneration using DNA microarray technology and then further explored the gene network using pathway analysis tools. Several cascades of gene components were induced or inhibited as a result of corresponding gene knockout under specific light conditions. Transducin deletion blocked the apoptotic signaling induced by exposure to low light conditions, and it did not require c-Fos/AP-1. Deletion of c-Fos blocked the apoptotic signaling induced by exposure to high intensity light. In the present study, we identified many gene transcripts that are essential for the initiation of light-induced rod degeneration and proposed several important networks that are involved in pro- and anti-apoptotic signaling. We also demonstrated the different cascades of gene components that participate in apoptotic signaling under specific light conditions.
Animals
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Apoptosis/radiation effects
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G-Protein-Coupled Receptor Kinase 1/genetics
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GTP-Binding Protein alpha Subunits/genetics
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*Gene Expression Profiling
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Genes, fos/genetics
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Light/adverse effects
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Light Signal Transduction/*genetics/physiology/radiation effects
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Mice
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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Retina/metabolism/pathology/radiation effects
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Retinal Degeneration/etiology/*genetics/physiopathology
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Transducin/genetics