Sustained neuroprotection from a single intravitreal injection of PGJ2 in a rodent model of anterior ischemic optic neuropathy.

Abstract

PURPOSE:

Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common cause of sudden optic nerve-related vision loss in persons older than 50 in the United States. There currently is no treatment for this disorder. We previously showed that systemic administration of 15-deoxy, delta (12, 14) prostaglandin J2 (PGJ2) is neuroprotective in our rodent model of AION (rAION). In this study, we determined if a single intravitreal (IVT) injection of PGJ2 is neuroprotective after rAION, and if this method of administration is toxic to the retina, optic nerve, or both.

METHODS:

TOXICITY was assessed after a single IVT injection of PGJ2 in one eye and PBS in the contralateral eye of normal, adult Long-Evans rats. EFFICACY was assessed by inducing rAION in one eye and injecting either PGJ2 or vehicle immediately following induction, with the fellow eye serving as naïve control. Visual evoked potentials (VEPs) and ERGs were performed before induction and at specific intervals thereafter. Animals were euthanized 30 days after induction, after which immunohistochemistry, transmission electron microscopy, and quantitative stereology of retinal ganglion cell (RGC) numbers were performed.

RESULTS:

TOXICITY:

IVT PGJ2 did not alter the VEP or ERG compared with PBS-injected control eyes, and neither IVT PGJ2 nor PBS reduced overall RGC numbers.

EFFICACY:

IVT PGJ2 preserved VEP amplitude, reduced optic nerve edema, and resulted in significant preservation of RGCs and axons in eyes with rAION.

CONCLUSIONS:

A single IVT injection of PGJ2 is nontoxic to the retina and optic nerve and neuroprotective when given immediately after rAION induction.

• Authors: Valerie Touitou, Mary A Johnson, Yan Guo, Neil R Miller, Steven L Bernstein
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 54 Issue 12 Pg. 7402-9 (Nov 11 2013) ISSN: 1552-5783 [Electronic] United States
• PMID: 24106118 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Neuroprotective Agents
• 9-deoxy-delta-9-prostaglandin D2
• Prostaglandin D2

Topics

• Animals
• Disease Models, Animal
• Electroretinography (drug effects)
• Evoked Potentials, Visual (drug effects)
• Intravitreal Injections
• Neuroprotective Agents (administration & dosage, adverse effects)
• Optic Neuropathy, Ischemic (drug therapy, pathology, physiopathology)
• Prostaglandin D2 (administration & dosage, adverse effects, analogs & derivatives)
• Rats
• Rats, Long-Evans
• Retinal Ganglion Cells (cytology)