Defective myelination in the optic nerve of the Browman-Wyse (BW) mutant rat.

The Browman-Wyse (BW) rat displays a spectrum of ocular abnormalities which include myelination by Schwann cells of retinal ganglion cell (RGC) axons within the retina. Immunohistochemical and ultrastructural studies of the optic nerves of adult BW rats (30-60 days of age) with myelinated intraretinal axons were performed. Although individual nerves displayed considerable morphological variability, all were characterized by an initial dysmyelinated proximal segment which was separated from a normally myelinated distal segment by a transitional junctional zone. The proximal segment contained axons which were predominantly unmyelinated: where myelination occurred, almost all sheaths were Po-positive, proteolipid protein-negative, and the myelinating cell was a Schwann cell. In the distal segment the distribution of myelinated axons appeared to be normal, sheaths were PLP+, and the myelinating cell was an oligodendrocyte. Within the proximal segment, axons that were myelinated by Schwann cells were isolated by a basal lamina and expanded extracellular spaces from the bulk of other RGC axons within the optic nerve. Few carbonic anhydrase (CAII)+ or GalC+ oligodendrocytes were seen in proximal segments that contained Schwann cells: anti-CAII antibody stained atypical cells within the proximal segments which did not resemble CAII+ oligodendrocytes in the distal segment, and which were probably GalC-. Astrocytes appeared normal throughout the length of the nerve, and there was no morphological specialization at the junctional zone similar to that at the lamina cribrosa. The possible source(s) of the intraneural Schwann cells, and the pathogenetic mechanisms underlying the aberrant myelination of RGC axons within the BW optic nerve are discussed.