IMMUNOHISTOCHEMICAL STUDIES ON NEUROFILAMENTOUS HYPERTROPHY IN DEGENERATING RETINAL TERMINALS OF THE OLIVARY PRETECTAL NUCLEUS IN THE RAT

Following section of the optic nerve, degenerating retinal terminals r eveal an accumulation of neurofilaments (neurofilamentous hypertrophy) as demonstrated by silver impregnation techniques or electron microsc opy. The present study examined degenerating retinal terminals by mean s of immunohistochemistry and antibodies specific for the triplet of n eurofilament proteins of low (NF-L), medium (NF-M), and high (NF-H) mo lecular weight class. Following unilateral optic nerve section in the rat and survival of 1, 2, 4, 8, and 21 days, brains were perfused with aldehyde fixative, sliced on a vibratome and stained for neurofilamen ts by using the peroxidase-antiperoxidase technique. Other brains were frozen, cut in the native state, and slide-mounted sections were fixe d by acetone. Side comparisons in visual pathways were made in frontal sections, taking advantage of the near complete crossing of retinal f ibers in the rat. Anterograde degeneration of axons occurred in the op tic tract and brachium colliculi. Changes of terminals were investigat ed in the olivary pretectal nucleus, which contains a dense aggregatio n of retinal terminals in the core region. The optic tract and brachiu m colliculi showed a reduction in immunostaining for neurofilament pro teins following axotomy. Within the core region of the olivary pretect al nucleus, strong increases of immunoreactivity of NF-L and NF-M were detected beginning at 2 days postlesion and persisting at 8 days. No changes in NF-H proteins were found in the terminal regions with three different antibody probes. The increase in immunostaining reflects th e accumulation of neurofilament proteins in the degenerating retinal t erminals, i.e., neurofilamentous hypertrophy. A combination of increas ed influx of neurofilaments into the terminals and decreased local deg radation by calcium-activated neutral protease might explain the accum ulations. The selective occurrence of NF-L and NF-M suggests molecular specificity of the degenerative process, which may be related to diff erences in axonal transport, integration into the stationary cytoskele ton, and phosphorylation state of different neurofilament proteins.