Abstract
• Background: Menkes' disease may be due to a lack or deficiency of copper in various organs. The macular mouse is known as a model for Menkes' disease. We examined melanin granules in the retinal pigment epithelium and the activity of cytochrome oxidase, a copper-containing enzyme, in the retinas of macular mice by electron microscopy. • Methods: In the retinas of hemizygote macular mice we demonstrated cytochemically (oxidative polymerization of diaminobenzidine to an osmophilic reaction product) the activity of cytochrome oxidase. The distribution of melanin granules in the retinal pigment epithelium related to the activity of another copper-containing enzyme, tyrosinase, was also studied. Stereological methods were applied to obtain quantitative data. • Results: In the retinal photoreceptor inner segments of the macular mouse, the mitochondria were more numerous than in normal littermates and they appeared swollen. There were fewer melanin granules in the retinal pigment epithelium of macular mice than in that of normal littermates. The cytochrome oxidase activity was significantly lower in the macular mice than in the controls. • Conclusion: Macular mice have lower activity of cytochrome oxidase and fewer melanin granules than do normal mice. Both changes may be related to copper deficiency. These results correspond to the retinal changes seen in patients with Menkes' disease.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aguilar MJ, Chadwick DL, Okuyama K, Kamoshita S (1966) Kinky hair disease. I. Clinical and pathological features. J Neuropath Exp Neurol 25: 507–522
Bray PF (1965) Sex-linked neurodegenerative disease associated with monithrix. Pediatrics 36: 417–420
Cotineau J, Rozelle A, Treppoz M (1978) La maladie de Menkes: a propos d'une nouvelle observation. J Fr Ophtalmol 2: 33–37
Dake Y (1992) Electron histochemical examination of cytochrome oxidase in the retinal photoreceptor cell of copper deficient rats. Acta Histochem Cytochem 25: 371–378
Danks DM, Stevens BJ, Campbell PE, Gillespie JM, Walker-Smith J, Blomfield J, Turner B (1972) Menkes' kinky hair syndrome. Lancet 1: 1100–1103
Ghadially FN (1988) Ultrastructural pathology of the cell and matrix, vol 1. Butterworths, London, pp 240–249
Heydorn K, Damsgaard E, Horn N, Mikkelsen M, Tygstrup I, Vestermark S, Weber J (1975) Extra-hepatic storage of copper. A male foetus suspected of Menkes' disease. Hum Genet 29: 171–175
Hirai K, Ogawa K (1986) Cytochemical quantitation of cytochrome oxidase activity in rat pulmonary alveolar epithelial cells and possible defect in type I cells. J Electron Microsc 35: 19–28
Hirai K, Ogawa K, Wang GY, Ueda T (1989) Varied cytochrome oxidase activities of the alveolar type I, type II and type III cells in rat lungs: quantitative cytochemistry. J Electron Microsc 38: 449–456
Meguro Y, Kodama H, Abe T, Kobayashi S, Kodama Y, Nishimura M (1991) Changes of copper level and cytochromec oxidase activity in the macular mouse with age. Brain Dev 13: 184–186
Menkes JH, Alter M, Steigleder GK, Weakley DR, Sung JH (1962) A sexlinked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Pediatrics 29: 764–779
Mishima H, Hasebe H, Fujita H (1978) Melanogenesis in the retinal pigment epithelial cell of the chick embryo. Dopa-reaction and electron microscopic autoradiography of3H-Dopa. Invest Ophthalmol Vis Sci 17: 403–411
Nagara H, Yajima K, Suzuki K (1980) An ultrastructural study on the cerebellum of the brindled mouse. Acta Neuropathol 52: 41–50
Nishimura M (1975) A new mutant mouse, Macular (Ml). Jikkendoubutsu 24: 185
Nishimura M (1989) Animal model for trace metal element deficient disease (particularly, mouse models for Menkes syndrome). Med Immunol 17: 725–733
Okuda K, Nasu K, Fujisaki H (1970) Electron microscopic observations on degenerating photoreceptor synapses of C3H (rodless) mice. Folia Ophthalmol Jap 21: 475–482
Prohaska JR, Wells WW (1974) Copper deficiency in the developing rat brain: a possible model for Menkes' steely-hair disease. J Neurochem 23: 91–98
Prohaska JR, Wells WW (1975) Copper deficiency in the developing rat brain: Evidence for abnormal mitochondria. J Neurochem 25: 221–228
Seelenfreund MH, Gartner S, Vinger PF (1968) The ocular pathology of Menkes' disease. (Kinky hair disease). Arch Ophthalmol 80: 718–720
Seligman AM, Karnovsky MJ, Wasserkrug HL, Hanker JS (1968) Nondroplet ultrastructural demonstration of cytochrome oxidase activity with a polymerizing osmophilic reagent, diaminobenzidine (DAB). J Cell Biol 38: 1–14
Tsurui S, Sugie H (1990) A pathophysiological study of macular mutant mouse as a model of human Menkes kinky hair disease. I. Copper contents and copper dependent enzyme activities in various organs. No To Hattatsu 22: 560–565
Wang GY, Hirai K, Odashima S (1990) Quantitative cytochemical studies of cytochrome oxidase activity in rat dorsal root ganglion cells. J Electron Microsc 39: 231–237
Wray SH, Kuwabara T, Sanderson P (1976) Menkes' kinky hair disease: a light and electron microscopic study of the eye. Invest Ophthalmol 15: 128–138
Yajima K, Suzuki K (1979) Neuronal degeneration in the brain of the brindled mouse. An ultrastructural study of the cerebral cortical neurons. Acta Neuropathol 45: 17–25
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mishima, K., Dake, Y., Amemiya, T. et al. Electron microscopic study of retinas of macular mice. Graefe's Arch Clin Exp Ophthalmol 234 (Suppl 1), S101–S105 (1996). https://doi.org/10.1007/BF02343056
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02343056