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(Investigative Ophthalmology and Visual Science. 2001;42:2679-2685.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

Abnormal Centrifugal Axons in Streptozotocin- Diabetic Rat Retinas

Matthew J. Gastinger1, Alistair J. Barber2, Sonny A. Khin2, Connie S. McRill2, Thomas W. Gardner2,3 and David W. Marshak1

1 From the Department of Neurobiology and Anatomy, University of Texas-Houston Medical School; and the 2 Departments of Ophthalmology and 3 Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, Pennsylvania.

PURPOSE. To characterize the effects of diabetes on the expression of histidine decarboxylase mRNA and on the morphology of the histaminergic centrifugal axons in the rat retina.

METHODS. Rats were made diabetic by streptozotocin. After 3 months, retinal histidine decarboxylase expression was analyzed by in situ hybridization in radial sections. Flatmount retinas from a second group of rats were labeled with an antiserum to histamine or an antibody to phosphorylated neurofilament protein.

RESULTS. Histidine decarboxylase mRNA was expressed in cells in the inner and outer nuclear layers of diabetic retinas, but not in normal retinas. However, immunoreactive (IR) histamine was not localized to perikarya in either the normal or the diabetic retinas. Instead, a population of centrifugal axons was labeled. These axons emerged from the optic disc and had varicose terminal branches in the inner plexiform layer (IPL) of the peripheral retina. Some branches ended on large retinal blood vessels and others in dense clusters in the IPL. In rats with streptozotocin-induced diabetes, the centrifugal axon terminals developed many large swellings that contained neurofilament immunoreactivity; these swellings were rare in normal retinas.

CONCLUSIONS. Diabetes perturbs the retinal histaminergic system, causing increases in histidine decarboxylase mRNA expression in neurons or glia and abnormal focal swellings on the centrifugal axons.




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