Purchase this article with an account.
FN Ross-Cisneros, N Aguirre, G Manfredi, SO Walker, MM Cruz, AA Sadun, V Carelli; Chloramphenicol-Induced Retinal Degeneration Mimics Kearns-Sayre and NARP Syndromes in Mice: A Model for Mitochondrial Retinal Disease . Invest. Ophthalmol. Vis. Sci. 2002;43(13):232.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose:To investigate the pathological changes in the retina and optic nerve of a mouse model of mitochondrial disease induced by high doses of chloramphenicol, a well- known inhibitor of mitochondrial protein synthesis, which can lead to respiratory chain deficiency. Methods: Adult B6SJL mice (90 days old) were treated with chloramphenicol succinate p.o. for 15 days at 500mg/kg/day or 1000mg/kg/day in separate groups. A third group served as a control. Mice were sacrificed and posterior poles of eyes and optic nerves proximal to the globe were processed for histological examination. Semi-thin sections were cut on an ultramicrotome. Posterior poles were cut horizontally and evaluated with Richardson's (a basophilic) stain for qualitative features. Optic nerves were cut in c.s. and stained using the PPD method for myelin. Images from four equally divided sectors/nerve were viewed at 1250x on a Zeiss Axioskop microscope and captured by a digital camera. Number vs. width of axonal profiles were examined with image analysis software. Results: (Qualitative) Posterior poles: Controls appeared normal. Both drug groups demonstrated severe (total) loss of the photoreceptor and outer nuclear layers.The inner plexiform layer appeared "granular". Many cells in the inner nuclear and ganglion cell layers looked "swollen". The RPE was observed to possess "denser" pigment in foci throughout the retina. Pigmented cells often "stacked" onto the optic disk. (Quantitative) Optic nerves (Width of Axonal Profiles in Microns): Controls- min. 0.20, max. 2.00, mean 0.65, SD 0.35, 500 mg/kg grp.-min. 0.20, max. 2.07, mean 0.72, SD 0.41, 1000 mg/kg grp.-min. 0.40, max. 3.67, mean 1.04, SD 0.67. Conclusion: High dose chloramphenicol induced devastating changes in the murine eye, most notably in the outer retina. Progression of degenerative features into the inner retina were also evident, resulting in preferential loss of small axons in the optic nerve. These features mimic the retinal dystrophy characteristically seen in mitochondrial encephalomyopathies such as Kearns-Sayre and NARP syndromes. However, the preferential involvement of small axons in the optic nerve mimics LHON where smaller fibers of the papillomacular bundle have been reported to be affected first.
This PDF is available to Subscribers Only