Abstract
Abstract: :
Purpose: To establish a rat model that simulates acute glaucoma in terms of retinal ganglion cell (RGC) death and the window for therapeutic vaccination with Cop-1. Methods: High intraocular pressure (IOP) was induced unilaterally in deeply anesthetized SPD rats by inserting a 30-gauge needle connected to a polyethylene tube through which normal saline (0.9%) in a bag held 1 meter above the rat's head was infused for 1 hour into the anterior chamber of the eye. IOP was assessed using a Tono-Pen tonometer (XL, Mentor¨). RGC survival 1 and 2 weeks after the high-pressure insult was assessed by counting the RGCs that had been retrogradely labeled with rhodamine dextran. Results: Saline infusion for 1 hour increased the IOP from 19(±4) to 44(±11) mm Hg. Baseline IOP values were restored after 24 hours. By 1 week after IOP insult, the RGC count had decreased by 30%. Vaccination with Cop-1 on the day of the insult prevented 50% of the IOP-induced RGC loss. Protection by Cop-1 was effective even if the vaccination was administered as late as 3 days after the insult. Conclusions: Raising the IOP to 44 mmHg for 1 hour causes death of RGCs in rats. Significant protection of RGCs from the IOP-induced death can be achieved by a single immunization with Cop-1. At least 50% of the potentially doomed RGCs can be rescued, suggesting that in the absence of treatment not all of the neuronal death in this model is a direct result of the IOP insult, but some neurons die because of the insult-induced hostility of the extracellular environment. These findings may have immediate application as a basis for glaucoma therapy, as Cop-1 (administered according to a different protocol) a clinically approved drug for multiple sclerosis.
Keywords: immunomodulation/immunoregulation