Localization of the neurotrophin receptor trkb in normal and glaucomatous monkey optic nerve heads

Purpose. To determine the distribution of the functional trkB receptor in the monkey optic nerve head prior to and after the induction of experimental glaucoma or experimental optic nerve atrophy. Methods. Ten monkeys with varying degrees of either unilateral experimental glaucoma (N=7) or optic nerve atrophy by transection (N=3) were studied. Both optic nerve heads (ONH) of each monkey were mildly fixed and processed into paraffin. Seven micron serial sections were stained by the streptavidin-biotin peroxidase technique using an antibody to the trkB (gp145) receptor This antibody recognizes a unique 15amino acid peptide within the catalytic domain of trkB, and does not cross-react with other trk receptor forms. The degree of glaucoma damage and optic atrophy were determined by examination of optic nerve cross-sections. Results. Axons of the normal ONH were uniformly stained. Additionally, glial elements (oligodendrocytes and astrocytes) were trkB positive, those just below the lamina cribrosa (LC) exhibiting more pronounced staining. The arachnoid/subarachnoid trabeculae, and the linings of the central retinal artery and choroidal vessels stained positively in both control and experimental ONHs. Intensely stained individual axons within neural bundles adjacent to and within the LC were observed in cases with early to moderate glaucoma damage and high IOP (range = 27 to 47). Glial elements were stained more intensely than in control eyes, their number and staining intensity increasing with the severity of glaucoma damage In the most severe glaucoma cases, focal areas of gliosis were intensely stained, filling in the remnants of neural pores and lining the thickened laminar beams. One month posttransection. numerous heavily stained axons were observed proximal to the location of the axotomy. Five months after transection, glial trkB staining was found throughout the nerve head, and no nerve fibers remained Conclusions. Expeiimental glaucoma leads to the accumulation of trkB neurotrophin receptor in axons at the optic nerve head. The accumulation of trkB receptor in this location suggests blocked axonal transport that may result in functional neurotrophin deprivation and ganglion cell death.