Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats

TLDR

It is unclear whether injury‑related processes in the optic nerve and retina affect all retinal ganglion cells uniformly or target specific subpopulations. The study aimed to examine short‑ and long‑term effects of optic nerve axotomy on retinal ganglion cell survival in adult rats. RGCs were retrogradely labelled and counted in flat‑mounted retinas at 2‑week to 20‑month intervals following optic nerve crush or cut at defined distances from the eye. RGC loss occurred in two phases: an abrupt loss within 2 weeks—more pronounced when the optic nerve was cut near the eye—and a slower, persistent decline with half‑survival times of ~1 month (intraorbital cut) to 6 months (intracranial crush), while about 5 % of cells survived up to 20 months, indicating that loss of terminal connectivity and additional mechanisms drive the protracted degeneration. © 1993 John Wiley & Sons, Inc.

Abstract

Abstract To investigate the short‐and long‐term effects of axotomy on the survival of central nervous system (CNS) neurons in adult rats, retinal ganglion cells (RGCs) were labelled retrogradely with the persistent market diI and their axons interrupted in the optic nerve (ON) by intracranial crush 8 or 10 mm from the eye or in intraorbital cut 0.5 or 3 mm from the eye. Labelled RGCs were counted in flat‐mounted retinas at intervals from 2 weeks to 20 months after axotomy. Two major patterns of RGC loss were observed: (1) an inital abrupt loss that was confined to the first 2 weeks after injury and was more severe when the ON was cut close to the eye; (2) a slower, persistent decline in RGC densities with one‐half survival times that ranged from approximately 1 month after intraorbital ON cut to 6 months after intracranial ON crush. A small population of RGCs (approximately 5%) survived for as long as 20 months after intraorbital axotomy. The initial loss of axotomized RGCs presumably results from time‐limited perturbations related to the position of the ON injury. A. persistent lack of terminal connectivity between RGCs and their targets in the brain may contribute to the subsequent, more protracted RGC loss, but the differences between intraorbital cut and intracranial crush suggest that additional mechanisms are involved. It is unclear whether the various injury‐related processes set in motion in both the ON and the retina exert random effects on all RGCs or act preferentially on subpopulations of these neurons. © 1993 John Wiley & Sons, Inc.