Neuroprotection of Ischemic Injury in Pig Retina, Part II: Ganglion Cell Rescue

Abstract

Purpose:: Evidence suggests that GDNF may enhance the survival of retinal ganglion cells (RGCs) when delivered via a bolus injection. We sought to investigate whether sustained delivery of GDNF over a 4-6 week period from polymer microspheres would lead to enhanced survival of RGCs in a porcine model of acute retinal ischemia induced by transient low ocular perfusion pressure (OPP).

Methods:: A model of low perfusion pressure in pigs was generated by monitoring and maintaining an IOP 5 mm Hg below the mean arterial pressure for 2 hours in the left eye. Three days later a small vitrectomy was performed over the optic nerve head in 10 animals and 0.1 ml of a solution of GDNF-containing or blank PLGA microspheres in PBS at a concentration of 10 mg/ml was injected. In 1 animal the microspheres were injected without vitrectomy. Eyes were fixed 4-6 weeks later and processed for histology and immunohistochemistry using an antibody (NeuN) to label RGCs. Right eyes served as controls.

Results:: In pressure-lesioned animals treated with blank microspheres the laminar organization of the inner retina was absent, whereas GDNF-treatment was associated with discernible inner plexiform, ganglion and nerve fiber layers. All 7 animals treated with GDNF-containing microspheres showed a markedly higher number of NeuN+ RGCs compared to the 4 pigs treated with blank microspheres (temporal retina: p=0.02, superior retina: p=0.01). In 2 of the GDNF-treated animals, RGC rescue of more than 50% was found in the region of the visual streak.

Conclusions:: In this pig model of acute retinal ischemia, sustained delivery of GDNF via biodegradable microspheres resulted in statistically significant rescue of ganglion cells. This treatment technique may be of interest in the setting of other conditions involving the loss of retinal neurons.

Keywords: ischemia • ganglion cells • neuroprotection