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Yang Liu, Colleen McDowell, Holly Tebow, Terri Beckwith, Robert J. Wordinger, Abbot F. Clark; Pattern ERG Deficits After Optic Nerve Crush In Mice. Invest. Ophthalmol. Vis. Sci. 2012;53(14):169.
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© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) and their axons. It is often modeled by optic nerve crush (ONC), as mechanical optic nerve damage results in the selective and progressive death of RGCs. This study was designed to characterize the morphological and functional changes of RGCs in response to ONC.
Pattern electroretinography (PERG), which reflects the function of RGCs, was performed from adult albino (BALB/cJ) and pigmented (C57/BL6) mice. Optic nerves of BALB/cJ mice with normal PERG responses were crushed unilaterally under direct visualization for 4 seconds, 1mm posterior to the globe. Three to twenty-eight days after the crush, survival of RGCs was analyzed in flat-mount retinas after Nissl staining. PERGs were recorded using pattern stimuli of 0.05 cyl/deg gratings reversing in contrast at 1 Hz presented at 100% contrast, and average ambient room lighting mean luminance.
PERG responses were obtained from all recorded eyes of C57/BL6 mice. The PERG showed a prominent positive wave that peaked, on average, around 70 ms after each reversal. However, only about 50% of recorded eyes of BALB/cJ mice had PERG responses, with smaller waveform (p<0.05) around 124 ms. Starting 7 days after intraorbital optic nerve crush, the loss of RGCs was continuous, and cell number in the RGC layer was significantly lower in the crushed eyes (p<0.001 for days 7, 14, 21, and 28). At 28 days post-crush, there were very few RGCs remaining in the RGC layer. PERGs were similar in waveform before and 3 days after crush. However, PERG amplitudes were significantly reduced 3 days after ONC (p<0.05) and totally eliminated 7 days after ONC.
Optic nerve crush induced progressive quantitative RGC cell death in a time dependent manner. PERG is a sensitive biomarker to monitor RGC functional changes induced by ONC. This model has the features of glaucomatous retinopathy and optic neuropathy, which will be useful for screening new neuroprotective agents.
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