Abstract
Purpose: :
Granulocyte-colony-stimulating factor (G-CSF) is a powerful and specific growth factor for neutrophilic granulocytes. G-CSF is currently used clinically for the treatment of neutropenia. Recently, G-CSF has been reported to exhibit novel anti-inflammatory and neuroprotective properties. Here, we investigated whether systemically administered G-CSF can protect retinal neurons against acute ischemic reperfusion injury.
Methods: :
Two groups of anesthetized adult male Lewis rats (n=8 per group) were subjected to an acute (45 min) episode of retinal ischemic injury followed by subcutaneous administration of vehicle (5% dextrose) or G-CSF (0.1 mg/kg/day) once per day x 5 days. Prior to and one-week following ischemic insult, retinal function was quantified by scotopic electroretinography. One week after ischemic insult, vehicle- or G-CSF-treated rats were sacrificed, eyes were enucleated, and post-fixed harvested retinas were analyzed morphologically. Expression of G-CSF receptor was analyzed by immunohistochemistry.
Results: :
Ischemic reperfusion injury elicited marked thinning of inner retinal layers in the vehicle-treated rats (29.1 ± 3.5µm vs. 57.7 ± 2.2µm, naïve untreated controls). By contrast, G-CSF-treatment partially prevented ischemic-mediated thinning of the inner retinal layers (46.2 ± 0.6 µm). ERG a- and b-wave amplitudes, an in vivo measure of retinal function, were significantly reduced (60-80%) following ischemic reperfusion injury. G-CSF-treatment largely prevented ischemic-mediated loss of retinal function. The G-CSF receptor was expressed by retinal neurons of the inner retinal layer.
Conclusions: :
G-CSF-treatment protects against acute ischemia-mediated changes in retinal morphology and function. These findings suggest that G-CSF may be of therapeutic value in treatment of acute retinal ischemic disorders.
Keywords: electrophysiology: non-clinical • retina • neuroprotection