JNK INHIBITOR EFFECTS ON RETINA MORPHOLOGY OBSERVED BY SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY IN MOUSE MODEL OF RETINAL ISCHEMIA/PERFUSION

Purpose: We hypothesize that inhibition of the JNK signaling pathway will protect the retina following ischemia reperfusion injury. Methods: JNK inhibitor, SP600125 will be intraperitoneally administered prior to retinal ischemia/reperfusion injury as well as daily for 28 days. The left eyes of female C57BL6/J mice will be cannulated with a 30-gauge needle for raising intraocular pressure to 120 mmHg for 60 min, followed by removal of the needle thus allowing retinal reperfusion. At 3, 7, 14, 21 and 28 days after I/R injury, retinal layers will be monitored by SD-OCT scanning. Thickness of the whole retina and each sub-retinal layer (e.g. inner plexiform layer, inner nuclear layer and outer nuclear layer) will be measured with SD-OCT software. Subsequently, changes in layer thickness will be statistically analyzed. The experiment will utilize three groups of five mice consisting of one control group, one ischemia/reperfusion group and one ischemia/reperfusion group with JNK inhibitor. Statistical analysis will be performed by using one-way ANOVA for group comparison. Results: SD-OCT scanning demonstrated similar retinal morphology compared to traditional histological techniques. Retinal thickness was reduced in the I/R eye in comparison with its non-pressured contralateral eye (right eye) after injury. Reduced retinal degeneration was seen in SP600125 treated mice. Conclusions: 1. SD-OCT visualized retinal morphology which is highly compatible to traditional histological assessment. 2. Retinal thickness was reduced in I/R eye in comparison with its control eye. 3. SP600125 administration to I/R eye show prevention of layer thickness degeneration indicating that JNK pathway contributes to pathogenesis following I/R injury. 4. The JNK signaling pathway is implicated in the inflammatory cascade. Further investigation is warranted to examine the possibility of the JNK signaling pathway as a future pharmacological drug target for I/R injury.