Axonal and vascular changes following injury to the rat's optic nerve.

The optic nerve of the rat has been examined by light and electron microscopy, and also for vascular permeability to fluorescently labelled albumin, 2 days to 34 weeks after crushing in the orbit. The operation was usually followed by loss of 20-70% of the retinal ganglion cells. Axons could be followed from the retina into the optic nerve at all postoperative times, but they always ended anterior to the lesion. Evidence of feeble regenerative growth of optic axons was seen in the first few postoperative weeks: bifurcating fibres and fibres that turned back towards the eye were present within the optic nerve anterior to the lesion. At the site of crushing, the optic nerve eventually became a thin cord of astroglia, surrounded and partly infiltrated by collagenous connective tissue. Long argyrophilic fibres were conspicuous in the intracranial part of the crushed optic nerve from the seventh to the fourteenth postoperative week. These were shown by electron microscopy to be degenerating myelinated axons that had not been phagocytosed. It was conceivable that axons from the contralateral retina could have sprouted at the chiasma and grown into the degenerated optic nerve. This possibility was excluded by tracing anterograde axonal transport of horseradish peroxidase injected into the contralateral eye. Intravenously injected fluorescent protein entered the connective tissue of the orbit and the connective tissue trabeculae of the optic nerve, but it did not permeate into the central nervous tissue except at the lamina cribrosa, where the optic axons pierce the sclera. Permeability at this site was the same on the operated and unoperated sides. Abnormal permeability of the vasculature was seen at the site of crushing the optic nerve. Fluorescence there was strongest in the first two postoperative weeks and was not seen after the third week. A much less conspicuous defect of barrier function occurred in the intracranial portion of the crushed optic nerve, from the seventh to the fourteenth postoperative week. The responses of the optic nerve of the rat to axotomy contrast markedly with those of the goldfish, in which the blood vessels become permeable to protein throughout the optic pathway and the axons regenerate successfully. Various attempts were made to increase or prolong the opening of the blood-optic nerve barrier in the rat, in the hope of enhancing axonal regeneration, but these endeavours were all unsuccessful.