Antibodies to heavy neurofilament subunit detect a subpopulation of damaged ganglion cells in retina

Abstract

Neurofilaments (NFs) consist of three protein subunits with apparent molecular weights of 68,000 (68K), 145K and 200K, which are found closely associated in most but not all locations in the nervous system^1–4. One of these exceptions is the inner retina of the mouse, where antibodies to 145K NFs label large ganglion cells throughout the extent of the cells, while antibodies to 200K NFs label only more distal portions of the optic axons but usually fail to label the ganglion cell somata and proximal axons^5,6. Very rarely, however, and more often in old mice, anti-200K NF antibodies do label a ganglion cell completely⁵. To determine whether these rare, completely labelled cells reflect a pathological alteration, we cut the optic axons, and report here that after a few days some of the axotomized cells could be labelled completely, in a Golgi-like fashion, by anti-200K NF antibodies. These cells seem to represent the population that forms the projection to the bulk of the lateral geniculate nucleus, as suggested by their size, distribution and projection pattern. Hence, antibodies to the heavy NF subunit in combination with lesions may allow selective retrograde tracing of a subpopulation of ganglion cells, and such antibodies can be used to detect damage in NF-rich neurones at a very early stage, long before they eventually degenerate.