Regenerative and other responses to injury in the retinal stump of the optic nerve in adult albino rats: transection of the intraorbital optic nerve.
The proximal stump of the optic nerve was examined by electron microscopy from 1 d to 8 wk (dpo/wpo) after intraorbital transection. At 1 dpo a layer of axonal, cytoplasmic and myelin debris approximately 15 microns thick was present at the cut end. A zone approximately 25 microns thick of abnormal and partly degenerate tissue composed of many swollen axons filled with organelles of predominantly abnormal appearance lay between the zone of debris and more proximal levels of the optic nerve, which retained a normal appearance. The earliest putative axonal sprouts were seen at 1 dpo in this zone. By 2 dpo, bundles of small nonmyelinated axons containing microtubules, almost certainly axonal sprouts, had grown out from more proximal regions of the proximal stump and extended as far as its cut end. By 3 dpo, large numbers of axonal sprouts, as well as large numbers of macrophages and newly formed blood vessels, were seen close to the cut end of the proximal stump. Glial cells were not seen to accompany these early outgrowing bundles of axonal sprouts. By 5 dpo, the number of sprouts and macrophages had increased; many bundles of sprouts were now in contact with the surface of astrocytes, which were partly covered by basal lamina. At 7 dpo most of the macrophages had disappeared from the most distal part of proximal stump and bundles of axonal sprouts, associated with astrocytes, which in some cases had penetrated and were fasciculating such bundles, were present at the cut end. The regenerating axonal sprouts in the scar-like tissue at the distal end of the proximal stump of the optic nerve declined in numbers sharply at 2 wpo and only a few sprout-like axonal profiles were present by 8 wpo. Thus while ultimately abortive the early regenerative response is vigorous and involves the outgrowth of a large number of axonal sprouts in the first week after injury.