glycogen and Retinal-Degeneration

Topics: Amyloid; Carbohydrate Metabolism, Inborn Errors; Chromosome Aberrations; Chromosome Disorders; Collagen; Cornea; Corneal Dystrophies, Hereditary; Corneal Opacity; Descemet Membrane; Epithelium; Female; Genes, Dominant; Genes, Recessive; Glycogen; Glycosaminoglycans; Histocytochemistry; Humans; Hyalin; Keratoconus; Male; Microscopy, Electron; Microscopy, Polarization; Pedigree; Retinal Degeneration

Topics: Angiokeratoma; Arthritis; Autopsy; Biopsy; Carbohydrate Metabolism, Inborn Errors; Central Nervous System Diseases; Child; Diffuse Cerebral Sclerosis of Schilder; Encephalitis; Encephalomyelitis; Gangliosides; Gaucher Disease; Glycogen; Glycosaminoglycans; Humans; Lipid Metabolism; Lipidoses; Medical History Taking; Metabolic Diseases; Mucopolysaccharidoses; Mucopolysaccharidosis IV; Multiple Sclerosis; Myelin Sheath; Nerve Degeneration; Neurons; Niemann-Pick Diseases; Retinal Degeneration; Slow Virus Diseases; Virus Diseases

The significance of glycogenosomes (glycogen bodies), frequently seen in peripheral neurites of aging rats, is unknown and their occurrence elsewhere in nervous tissue is poorly documented. During the course of another study these bodies were observed by light microscopy in the visual pathways of aging rats where they have not previously been noted, and this report documents their occurrence, localisation and changes in density with age. Using the periodic acid-Schiff stain, small brightly red-staining bodies, digested by diastase and containing beta-glycogen particles, were seen in increasing numbers in the neuropil of the superior colliculi in brain sections from animals of 5 months of age onwards. From 1 year until more than 2 years of age they steadily became more numerous in the outer one third of the superior colliculus, but remained small, rarely exceeding 4 microm. They were also found at later times in small numbers lying singly in the optic tract, the optic chiasm and optic nerves, although rarely in lateral geniculate nuclei. Similar bodies were also found to accumulate with age in the retinal photoreceptor cell layer. Changes in their densities and size with age in both regions have been documented and it is suggested that, while their occurrence in retinal photoreceptor cells may be due to sustained light damage leading to mitochondrial oxidative stress, it is difficult to implicate this mechanism for their occurrence in retino-tectal nerve fibres. The role of physical trauma, suggested for the presence of these bodies in aging peripheral axons, can be excluded and they appear not to be related to polyglucosan bodies.

Topics: Aging; Animals; Brain Chemistry; Female; Glycogen; Male; Microscopy, Electron; Mitochondria; Nerve Fibers, Myelinated; Neurons; Rats; Retinal Degeneration; Retinal Ganglion Cells; Superior Colliculi; Visual Pathways

Electroretinographic and cyclic nucleotide metabolism studies have established that low-level lead exposure during early postnatal development results in long-term selective rod deficits. To determine whether there was a corresponding selective rod photoreceptor cell degeneration we examined retinas of adult rats exposed to low-level lead during development using light and electron microscopy. In all retinal regions, a rod but not cone cell degeneration was observed. Overall, 20% of the rod cells were lost. Moreover, two specific regional differences were found. Degeneration was much greater in the inferior (-25%) than superior (-15%) retina and greater in the posterior (-22%) than peripheral (-17%) retina. The latter pattern indicates a central-peripheral gradient of degeneration. Total retinal thickness decreased 15-20%, which reflects cell loss in the outer and inner nuclear layers. Ultrastructurally, the most obvious lead-induced alterations were swollen and disorganized rod outer segments and large accumulations of beta-glycogen particles in rod photoreceptor mitochondria. Glycogen accumulations were heaviest in rod inner segment mitochondria followed by rod axon and synaptic terminal mitochondria. Possible cellular mechanisms of action responsible for these lead-induced retinal alterations include an inhibition of retinal cyclic GMP phosphodiesterase and the resultant elevation of cyclic GMP, an inhibition of intermediary metabolism, and/or an alteration in calcium metabolism. In addition, the thinning of the inner nuclear layers could be due to transneuronal degeneration. As noted in our preceding paper, the first possibility has been demonstrated in rats similarly exposed to lead. These quantitative histological results, in combination with the ERG and biochemical results in the preceding paper, demonstrate that low-level lead exposure during early postnatal development produces long-term selective rod functional deficits and degeneration.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Animals; Cyclic GMP; Female; Glycogen; Lead; Microscopy, Electron; Mitochondria; Photoreceptor Cells; Rats; Retinal Degeneration; Rod Cell Outer Segment

Topics: Congenital Hypothyroidism; Female; Glycogen; Humans; Ichthyosis; Infant; Intellectual Disability; Linoleic Acids; Lipid Metabolism; Liver; Liver Glycogen; Microscopy, Electron; Muscle Spasticity; Myxedema; Palmitic Acids; Retinal Degeneration