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Jie Fan, Bill X. Wu, Yusuf A. Hannun, Craig E. Crosson; Acid Sphigomylelinase Plays a Role in IR-induced Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6584.
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© ARVO (1962-2015); The Authors (2016-present)
It is known that acid sphingomyelinase (ASM) is an important sensor in inflammatory cytokine and apoptotic signaling. It catalyzes the hydrolysis of sphingomyelin to ceramide, a key mediator of cell-stress responses and cell death. However, the role(s) of ASM in retinal neuronal degeneration have not been investigated. The purpose of this study is to investigate whether ASM plays a critical role in retinal ischemic injury.
ASM+/-mice and wild-type (WT) littermates were evaluated for changes in retinal function and morphology following retinal ischemia. Retinal ischemic injury was induced by elevating intraocular pressure to 140mmHg for 50 minutes. Seven days post ischemia, retinal function and morphology were assessed by electroretinogram(ERG), and microscopic examination, respectively.
In WT mice, retina ischemia significantly decreased mean a- and b-wave amplitudes by 43±4.3 and 82±2.4%, respectively, when compared to contralateral control eyes. In ASM+/- mice, retina ischemia also significantly decreased mean a- and b-wave amplitudes by 28±7.8 and 67±13.2%; respectively; however, this decline in both a- and b-wave amplitudes was significantly less than that observed in WT mice. Morphometric analysis of ischemic eyes from WT mice demonstrated significant decreases in inner nuclear layer and inner plexiform layer thickness of 43±4.6 and 77±2.3%, respectively, and a 65% decrease in cell bodies in the ganglion cell layer, when compared to control eyes. The ischemic eyes from ASM+/- mice revealed a decrease in the inner nuclear layer and inner plexiform layer thickness of 22±8.3 and 58±6.1%, respectively, when compared to control eyes; but this decrease was significantly less than that observed in WT eyes. In addition, significantly more surviving ganglion cell bodies were observed in ischemic eyes from ASM+/- compared to WT mice. No ERG or morphological differences were detected between WT and ASM+/- control eyes.
Our ERG and retinal morphology results demonstrate that the reduction in ASM expression provides partial protection from ischemic injury. Hence, the production of ceramide and subsequent mediators likely play an important role in ischemic retinal injury. Inhibition of ASM may present new opportunities for the treatment of retinal ischemic disorders.
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