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D. R. Morhardt, T. E. Krahe, W. Guido, C. K. J. Chen; Normal Retinofugal Projections in Photoreceptor Degenerated Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1431.
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Photoreceptor degeneration is a common cause of blindness, affecting a broad range of ages and demographics. Recent studies demonstrate that photoreceptor degeneration triggers neuronal, glial, and vascular remodeling of the retina in humans and rodents. The impact of photoreceptor degeneration on the structure and function of central visual targets is not well understood. If central pathways are compromised after the degeneration of photoreceptors, retina-based treatments such as retinal prosthesis and retinal gene therapy will have limited restorative value. Here, we studied retinal degeneration models with different degrees of retinal remodeling and asked how these conditions affect the structure and function of retinofugal projections long after the loss of all photoreceptors.
We used two mouse models of photoreceptor degeneration: RhoΔCT mice with little apparent remodeling and the TG9N mice with early and aggressive remodeling (Jones, et al, JCN, 2003). We made intravitreal injections with Alexa Fluor-conjugated cholera toxin B (CTB) to anterogradely label and visualize eye-specific retinal projections in central visual structures. We also examined whether retinal projections make functional connections to central visual targets by examining the consensual pupillary light reflex (PLR) and by recording synaptic responses of relay cells in the lateral geniculate nucleus (LGN) evoked by electrical stimulation of the optic tract.
We found that after photoreceptor degeneration, retinal innervation, topography, and eye-specific patterning are largely preserved in recipient targets including suprachiasmatic nucleus, LGN, pretectal nucleus and superior colliculus. In LGN, the pattern of innervation and the degree of segregation of crossed and uncrossed retinal projections were indistinguishable from age-matched controls. All animals displayed comparable PLRs at 12,000 cd/m2 light intensity. In vitro recordings in LGN indicated a functional retinogeniculate synapse. In both models we could evoke postsynaptic responses that were similar to age-matched controls.
In the RhoΔCT and the TG9N mouse models, neither photoreceptor degeneration nor retinal remodeling grossly affects the structural and functional state of retinofugal projections.
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