Olfactory Ensheathing Cells Rescue Optic Nerve Fibers in a Rat Glaucoma Model

Abstract

Purpose: To determine if transplantation of olfactory ensheathing cells (OECs) can reduce loss of optic nerve axons after raised intraocular pressure (IOP) in the rat.Methods: OECs cultured from the adult olfactory mucosa were transplanted into the region of the optic disc. The IOP was raised by injection of magnetic microspheres into the anterior chamber.Results: At 4 weeks after raising the IOP, the transplanted OECs had migrated into the dorsal area of the optic nerve head (ONH) where they surrounded the optic nerve fibers with a non-myelinated ensheathment. The mean amount of damage to the ONH astrocytic area in rats was 51.0% compared with 85.8% in those without OEC transplants (P , 0.02) and the mean loss of axons in the optic nerve was 51.0% compared with 80.3% in the absence of OECs (P , 0.01). Conclusions:OECs transplanted into the region of the ONH of the rat can reduce the loss of axons and the damage to ONH astrocytes caused by raised IOP.Translational Relevance: Confirmation of these preliminary experimental data, further understanding of possible mechanisms of axonal protection by OECs, and the longer-term time course of protection could provide a basis for future human clinical trials of autografted OECs, which would be available from autologous nasal epithelial biopsies.

An energy theory of glaucoma

“…The means ± SEM of four consecutive readings of IOP were 10.0 ± 0.75 mm Hg ( n = 28) before injection, 17.7 ± 0.80 ( n = 6) at 4 days, 20.1 ± 1.29 ( n = 8) at 7 days, 24.3 ± 3.71 ( n = 8) at 14 days, and 13.4 ± 1.14 ( n = 6) at 28 days. In the present series of rats the IOP measurements under combined general and local anaesthesia were considerably lower than in the previous series (Dai et al, ) where only local anaesthesia was used.…”

“…We recently presented evidence that transplanted OECs are able to ensheath RGC axons, induce angiogenesis and reduce the degradation of the FAST array caused by raised IOP (Dai et al, ). We suggest that the ensheathment of the axons may preserve their vital energy input, and that the angiogenesis induced by the transplants may restore the blood supply to the remaining FASTs (Figs.…”

A rat experimental model of glaucoma incorporating rapid-onset elevation of intraocular pressure

“…Samsel et al proposed a novel “Bead Model” in which magnetic particles could cause highly elevated IOP values and showed that this resulted in severe axon damage within 4 weeks. The short duration and severe damage evoked by this model can be classified as acute neuropathy and not chronic glaucomatous damage, although IOP elevation is the basic mechanism through which the nerves are injured252627.…”

Transplantation of cultured olfactory mucosal cells rescues optic nerve axons in a rat glaucoma model

“…In our previous studies we have demonstrated that transplantation of cultured olfactory mucosal cells (OMCs) consisting mainly of OECs and ONFs before raising the IOP in a rat model could reduce the damage to ONH astrocytes and moderate the loss of optic nerve axons (Dai et al, 2012b).…”