Abstract
Purpose: :
To test the hypothesis that retinal ganglion cell (RGC) dendrite atrophy can be reversed in experimental glaucoma by the normalisation of intraocular pressure and disruption of the retinal perineuronal net (PNN).
Methods: :
Unilateral glaucoma was induced in adult male Norwegian Brown rats by the anterior chamber injection of paramagnetic polystyrene microspheres. IOPs were elevated for 2-4 weeks and then reduced, either spontaneously or by the topical administration of Azarga (Alcon). Chondroitinase ABC (chABC) was injected intravitreally into the glaucomatous eyes to digest the PNN. RGC dendritic morphology was determined by diolistic labelling (Gene Gun, BioRad) with DiI. RGCs were imaged by confocal microscopy and changes in dendritic structure quantified by Sholl analysis.
Results: :
Elevated IOPs were induced in 61 rats, with a mean elevation of 5.8 mmHg±1.0 (SEM) relative to contralateral control eyes. The mean duration of sustained IOP elevation (>5 mm Hg control eye, >= 7 consecutive days) following a single injection was 12.8 days ± 0.9 (SEM) and was associated with a 36.4% ± 2.4 (SEM) reduction in RGC layer cells. The areas under the Sholl (AUC) curves were reduced by 28.0% ± 25.1(SD) in untreated glaucomatous eyes. In ChABC-treated eyes, the AUC was increased by 79.8% ± 101.6%(SD) compared with glaucomatous untreated eyes. The number of bifurcations and the total dendritic length were significantly increased in chABC-treated eyes compared to the glaucomatous untreated eyes (55.8% ± 66.8% (SEM) and 43.5% ± 39.1% (SEM), respectively, P <0.05). The number of bifurcations in chABC-treated eyes did not differ from contralateral untreated (non-glaucomatous) eyes, whereas the total dendritic length was increased by 22.7% ± 27.6% (SEM),(P<0.05).
Conclusions: :
Digestion of the PNN in eyes with experimental glaucoma in which the IOP has normalised can facilitate recovery in the dendritic structure of retinal ganglion cells. These changes could provide a neural substrate for the partial restoration of visual function in glaucoma.
Keywords: ganglion cells • regeneration • plasticity