Transgenic mice expressing cyan fluorescent protein as a reporter strain to detect the effects of rotenone toxicity on retinal ganglion cells.
This is the first study using a reporter transgenic model to investigate the effects of an environmental toxin on the retina. Rotenone is a widely used pesticide that inhibits mitochondrial complex I and produces neurotoxicity. Previous studies demonstrated the time course and dose response of rotenone toxicity on retinal ganglion cells (RGC). However, previous analyses of rotenone-induced retinotoxicity provided little detail of the optic nerve axons and cellular pathology. These limitations were successfully surmounted by using a transgenic mouse line shown to express cyan fluorescent protein (CFP) in neurons, including RGC, under regulatory elements of the human the thy1.1 promoter (thy-CFP). Data showed that CFP expression is limited to RGC and their processes in the retina of thy-CFP mice. Eyes exposed to the pesticide rotenone displayed marked alterations in RGC morphology, inner plexiform layer, optic disc, and optic nerves. After 24 h, the number of CFP-labeled RGC was reduced 50%. Correlated with a loss of RGC bodies was an approximate 50% reduction in CFP fluorescence intensity at the optic disc. The findings showed that rotenone-induced degeneration of RGC and their processes can be visualized with exquisite detail in thy-CFP mice, and that this approach may provide a novel and effective way to monitor the association between environmental toxins and neurodegeneration in living animals.
Hayworth
C R
CR
Institute for Neuroscience and Division of Pharmacology and Toxicology, University of Texas at Austin, Austin, TX 78712-0187, USA.
Rojas
J C
JC
Gonzalez-Lima
F
F
D000818:Animals; D049452:Green Fluorescent Proteins / Q000187:drug effects* / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000473:pathology; D012402:Rotenone / Q000633:toxicity*
C485182:Cyan Fluorescent Protein; D007306:Insecticides; D012402:Rotenone; D049452:Green Fluorescent Proteins