Abstract
To study the effects of prenatal cocaine-exposure on the developing retinal ganglion cell layer of the rat, female Wistar rats were administered subcutaneously (sc) cocaine hydrochloride (60 mg/kg body wt/d) or saline, or were not manipulated from gestational d 8–22. Male offspring were sacrificed at postnatal day 14 and 30. Radial semithin sections of epon-embedded flat mounts of the retinal quadrants were used to evaluate the following parameters along the centroperipheral axis:
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1.
Thickness of ganglion cell plus nerve fiber layer;
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2.
Nuclear size of ganglion cell layer neurons; and
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3.
Linear density (number per unit length) of ganglion cell layer neurons.
To study the effects of cocaine and age on the retinal areas (temporal/nasal, dorsal/ventral), a repeated measures analysis of variance was used for each of the parameters mentioned above. All parameters were affected by prenatal exposure to cocaine. The thickness of the ganglion cell plus nerve fiber layer was reduced in cocaine-exposed rats in comparison with the saline group. Nuclear diameters were smaller in the cocaine than in the saline and control groups. The linear density was higher in the cocaine-exposed group than in the control and saline groups. The linear decrease in the linear density from postnatal day 14–30 was higher in the cocaine-exposed rats than in the saline group; the decrease in the linear density along the centroperipheral axis found in both the control and saline groups was not significant in the cocaine-treated group. These morphometric findings strongly support the view that prenatal cocaine-exposure induces marked changes in the organization of the developing retina.
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References
Akbari H. M. and Azmitia E. C. (1992) Increased tyrosine hydroxylase immunoreactivity in the rat cortex following prenatal cocaine exposure.Dev. Brain Res. 66, 277–281.
Borges J., Edward D., and Tso M. O. M. (1990) A comparative study of photo injury in four inbred strains of albino rats.Curr. Eye Res. 9, 799–803.
Chasnoff I. J., Burns K. A., Burns W. J., and Schnoll S. H. (1986) Prenatal drug exposure: effects on neonatal and infant growth and development.Neurobehav. Toxicol. Teratol. 8, 357–362.
Church M. W., Overbeck G. W., and Andrzejczak A. L. (1990) Prenatal cocaine-exposure in the Long-Evans rat: I. Dose-dependent effects on gestation, mortality, and postnatal maturation.Neurotoxicol. Teratol. 12, 327–334.
Church M. W. and Overbeck G. W. (1991) Sensorioneural hearing loss as evidenced by the auditory brainstem response following prenatal cocaine exposure in the Long-Evans rat.Tetratology 43, 561–570.
Dixon S. D., Coem R. W., and Crutchfield S. (1987) Visual dysfunction in cocaine-exposed infants.Pediatr. Res. 21, 395A.
Dominguez R. D., Vila-Coro A. A., Slopis J. M., and Bohan T. P. (1991) Brain and ocular abnormalities in infants with in utero exposure to cocaine and other street drugs.Am. J. Dis. Child. 145, 688–695.
Dubin M. W., Stark L. A., and Archer S. M. (1986) A role for action-potential activity in the development of neuronal connections in the kitten retinogeniculate pathway.J. Neurosci. 6, 1021–1036.
Ferriero D. M., Kobori J. A., Good W. V., and Golabi M. (1989) Retinal defects in cocaine-exposed infants.Ann. Neurol. 26, 458.
Good W. V., Ferriero D. M., Golabi M., and Kobori J. A. (1992) Abnormalities of the visual system in infants exposed to cocaine.Ophthalmology 99, 341–346.
Horsburgh G. M. and Sefton A. J. (1987) Cellular degeneration and synaptogenesis in the developing retina of the rat.J. Comp. Neurol. 263, 553–566.
Hughes W. F. (1991) Quantitation of ischemic damage in the rat retina.Exp. Eye Res. 53, 573–582.
Isenberg S. J., Spierer A., and Inkelis S. (1987) Ocular signs of cocaine intoxication in neonates.Am. J. Ophthalmol. 103, 211–214.
Kalil R. E., Dubin M. W., Scott G., and Stark L. A. (1986) Elimination of action potential blocks the structural development of retinogeniculate synapses.Nature 323, 146–148.
Linden R. and Perry V. H. (1982) Ganglion cell death within the developing retina: a regulatory role for retinal dendrites?Neuroscience 11, 2813–2827.
Mahalik M. P., Gautieri R. F., and Mann D. E. Jr. (1980) Teratogenic potential of cocaine hydrochloride in CF-1 mice.J. Pharm. Sci. 69, 703–706.
Palay S. L. and Chan-Palay V. (1974)Cerebellar Cortex-Cytology and Organization. Springer-Verlag, Berlin.
Perry V. H. (1981) Evidence for an amacrine cell system in the ganglion cell layer of the rat retina.Neuroscience 6, 931–944.
Potts R. A., Dreher B., and Bennett M. R. (1982) The loss of ganglion cells in the developing retina of the rat.Dev. Brain Res. 3, 481–486.
Reese B. B. and Colello R. J. (1992) Neurogenesis in the retinal ganglion cell layer of the rat.Neuroscience 46, 419–429.
Salamy A., Dark K., Salfi M., Shah S., and Peeke H. V. S. (1992) Perinatal cocaine-exposure and functional brainstem development in the rat.Brain Res. 598, 307–310.
Seidler F. J. and Slotkin T. A. (1993) Prenatal cocaine and cell development in rat brain regions: effects on ornithine decarboxylase and macromolecules.Brain Res. Bull. 30, 91–99.
Sengelaub D. R. and Finlay B. L. (1982) Cell death in the mammalian visual system during normal development: I. Retinal ganglion cells.J. Comp. Neurol. 204, 311–317.
Shah N. S., May D. A., and Yates Y. D. (1980) Disposition of levo [3H] cocaine in pregnant and non-pregnant mice.Toxicol. Appl. Pharmacol. 53, 279–284.
Silva-Araújo A., Salgado-Borges J., and Tavares M. A. (1991) Morphological changes in the optic nerve after chronic exposure of neonatal rats to cocaine and amphetamine.Ophthalmic Res. 23, 295–302.
Silva-Araújo A., Salgado-Borges J., Cardoso V., Silva M. C., Castro-Correia J., and Tavares M. A. (1993) Changes in retinal ganglion cell layer and optic nerve of rats exposed neonatally to cocaine.Exp. Eye Res. 56, 199–206.
Silva M. C., Silva-Araújo A., Abreu S., Xavier M. R., Monteiro S. L., and Tavares M. A. (1995) Effects of prenatal cocaine exposure on postnatal growth patterns of male Wistar rats.Neurotoxicol. Teratol. in press.
Spear L. P., Kirstein C. L., Bell J., Yoottanasumpun V., Greenbaum R., O'Shea J., Hoffman H., and Spear N. E. (1989) Effects of prenatal cocaine-exposure on behavior during the early postnatal period.Neurotoxicol. Teratol. 11, 57–63.
Teske M. P. and Trese M. T. (1987) Retinopathy of prematurity-like fundus and persistent primary vitreous associated with maternal cocaine use.Am. J. Ophthalmol. 103, 719–720.
Volpe J. J. (1992) Effect of cocaine use on the fetus.N. Engl. J. Med. 327, 399–407.
Webster W. S., Woodman P. D. C. B., Lipson A. H., and Ritchie H. E. (1991) Fetal brain damage in the rat following prenatal exposure to cocaine.Neurotoxicol. Teratol. 13, 621–626.
Weibel E. R. (1979)Stereological Methods. Practical Methods for Biological Morphometry, vol. 1. Academic, London.
Winer B. J. (1991)Statistical Principles in Experimental Design, McGraw-Hill, New York, pp. 497–582.
Woods J. R., Plessinger M. A., and Clark K. E. (1987) Effect of cocaine on uterine blood flow and fetal oxygenation.J. Am. Med. Assoc. 257, 957–961.
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Silva-Araújo, A., Silva, M.C., Abreu-Dias, P. et al. Effects of prenatal cocaine exposure in the retinal ganglion cell layer of the rat. Mol Neurobiol 11, 87–97 (1995). https://doi.org/10.1007/BF02740687
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DOI: https://doi.org/10.1007/BF02740687