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Wei Wang, Juan Fernandez de Castro, Eric Vukmanic, Liang Zhou, Douglas Emery, Paul J. DeMarco, Henry J. Kaplan, Douglas C. Dean; Selective Rod Degeneration and Partial Cone Inactivation Characterize an Iodoacetic Acid Model of Swine Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2011;52(11):7917-7923. doi: https://doi.org/10.1167/iovs.11-7849.
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Transgenic pigs carrying a mutant human rhodopsin transgene have been developed as a large animal model of retinitis pigmentosa (RP). This model displays some key features of human RP, but the time course of disease progression makes this model costly, time consuming, and difficult to study because of the size of the animals at end-stage disease. Here, the authors evaluate an iodoacetic acid (IAA) model of photoreceptor degeneration in the pig as an alternative model that shares features of the transgenic pig and human RP.
IAA blocks glycolysis, thereby inhibiting photoreceptor function. The effect of the intravenous injection of IAA on swine rod and cone photoreceptor viability and morphology was followed by histologic evaluation of different regions of the retina using hematoxylin and eosin and immunostaining. Rod and cone function was analyzed by full-field electroretinography and multifocal electroretinography.
IAA led to specific loss of rods in a central-to-peripheral retinal gradient. Although cones were resistant, they showed shortened outer segments, loss of bipolar cell synaptic connections, and a diminished flicker ERG, hallmarks of transition to cone dysfunction in RP patients.
IAA provides an alternative rod-dominant model of retinal damage that shares a surprising number of features with the pig transgenic model of RP and with human RP. This IAA model is cost-effective and rapid, ensuring that the size of the animals does not become prohibitive for end-stage evaluation or therapeutic intervention.
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