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Tsung-Han Chou, Mario J Rojas, Ning Wang, Yihui Chen, Rong Wen, Vittorio Porciatti; Loss and recovery of retinal ganglion cell function after distal injury of the retino-collicular pathway. Invest. Ophthalmol. Vis. Sci. 2014;55(13):2394.
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© ARVO (1962-2015); The Authors (2016-present)
Intrinsic survival mechanisms of injured neurons are difficult to study because of concurrent destructive mechanisms leading to cell death. Here we investigate adaptive plasticity of retinal ganglion cells (RGCs) following superior colliculus (SC) injury in mice, a model that does not cause RGC death over several months (Yang et al, IOVS 2013).
RGC function (pattern ERG, PERG), outer retina function (photopic ERG, FERG) and inner/outer retina thickness (SD-OCT) were serially assessed in anesthetized C57BL/6J mice (n=14) at closely-spaced time points before and after surgical ablation of the superficial layers of the right SC. Integrity of optic nerve axons and transport was established by means of intravitreal injections of cholera toxin B (CTB). At endpoint, confocal microscopic analysis of RGCs was performed on TUJ1-labeled retinal flat mounts. BDNF expression was quantified in Western blots of retina homogenates.
After right SC lesion, the PERG amplitude did not change in the right eye but rapidly decreased in the left eye to 44% of baseline, recovered slowly after one week to reach 68% of baseline at one month and then remained stable over three months (ANOVA, P<0.001). CTB-labeled optic nerves and tracts were similar in the two eyes. After SC lesions, OCT-determined inner retina thickness (ILM+RNFL+GCL+IPL) remained normal in the left eye for about one week and then significantly thinned by about 4 µm (P<0.01), remaining at reduced thickness thereafter. At the three-month endpoint, the mean RGC soma size was reduced in the left eye while RGC density was normal, and BDNF expression was increased (P<0.01). The FERG was unchanged.
After SC injury, RGC function undergoes three distinct phases—sudden loss, slow recovery, stabilization at a subnormal level. The PERG plateau level is associated with inner retina thinning but not cell death, normal axonal transport and BDNF overexpression. These structural-functional-molecular changes indicate that RGCs have an intrinsic ability to reorganize and repair themselves to regain function after injury. The SC-lesion model is useful to investigate intrinsic survival mechanisms of RGCs.
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