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Byung-Jin Kim, Robert J. Wordinger, Abbot F. Clark; Pathologic Progression Of Retinal Ischemia And Reperfusion Injury In Mice Associated With Defective Retinal Function. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2477.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ischemia/reperfusion (I/R) is an important cause of visual impairment in various ocular diseases such as retinal vascular occlusion, diabetic retinopathy, glaucoma and ocualr trauma. Although mouse models of I/R have been broadly used, pathological structural and functional progression have not been clearly defined. In this study, we characterized progression of pathogenesis of mouse I/R model by analyzing morphological and functional changes in the retina.
Left eyes of anesthetized female C57BL6/J mice were cannulated with a 30-gauge needle, and intraocular pressure was raised to 120 mmHg for 60 min, followed by removal of the needle to allow reperfusion of retina. At 3, 7, 14, 21 and 28 days after I/R injury, retinal layers were monitored by SD-OCT scanning followed by histological assessment of H&E stained retinal cross-sections. Cell number in retinal ganglion cell (RGC) layer was also counted. In addition, retinal function was measured by scotopic ERG.
Retinal thickness in left eyes was significantly increased (p<0.05) 3 days after I/R injury by both H&E staining and SD-OCT scanning, but progressively diminished and significantly decreased (p<0.05) at 21-28 days compared to contralateral control eyes. The most significant changes were observed in the inner plexiform layer (IPL) and the inner nuclear layer (INL). Cell number in RGC layer was also significantly decreased (p<0.05) 14-28 days after I/R injury. In addition, retinal detachment was observed 3 & 7 days after I/R injury and appreared to be re-attached by day 14. Both the magnitude and implicit time of ERG b-waves were significantly impaired (p<0.05) in I/R eye from 7-28 days after injury. Interestingly, the a-wave in I/R eyes was significantly impaired in magnitude and implicit time through 21 days (p<0.05) but recovered 28 days after injury.
Pressure-induced I/R resulted in significant reduction of inner-retinal layer thickness 14-28 days after I/R, and these changes were significantly associated with impaired ERG b-wave responses. These data demonstrate that inner retinal layers are primarily sensitive to I/R injury, accompanied by structural and functional degeneration. Our results also showed that retinal detachment was occurred at 3-7 days, which caused impairment of photoreceptor a-waves and recovered 28 days after I/R injury. Future studies will identify cellular and molecular mechanisms associated with I/R damage to the retina, as well as the optic nerve and visual axis in the brain.
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