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Retinal remodeling

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Abstract

Retinal photoreceptor degeneration takes many forms. Mutations in rhodopsin genes or disorders of the retinal pigment epithelium, defects in the adenosine triphosphate binding cassette transporter, ABCR gene defects, receptor tyrosine kinase defects, ciliopathies and transport defects, defects in both transducin and arrestin, defects in rod cyclic guanosine 3′,5′-monophosphate phosphodiesterase, peripherin defects, defects in metabotropic glutamate receptors, synthetic enzymatic defects, defects in genes associated with signaling, and many more can all result in retinal degenerative disease like retinitis pigmentosa (RP) or RP-like disorders. Age-related macular degeneration (AMD) and AMD-like disorders are possibly due to a constellation of potential gene targets and gene/gene interactions, while other defects result in diabetic retinopathy or glaucoma. However, all of these insults as well as traumatic insults to the retina result in retinal remodeling. Retinal remodeling is a universal finding subsequent to retinal degenerative disease that results in deafferentation of the neural retina from photoreceptor input as downstream neuronal elements respond to loss of input with negative plasticity. This negative plasticity is not passive in the face of photoreceptor degeneration, with a phased revision of retinal structure and function found at the molecular, synaptic, cell, and tissue levels involving all cell classes in the retina, including neurons and glia. Retinal remodeling has direct implications for the rescue of vision loss through bionic or biological approaches, as circuit revision in the retina corrupts any potential surrogate photoreceptor input to a remnant neural retina. However, there are a number of potential opportunities for intervention that are revealed through the study of retinal remodeling, including therapies that are designed to slow down photoreceptor loss, interventions that are designed to limit or arrest remodeling events, and optogenetic approaches that target appropriate classes of neurons in the remnant neural retina.

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Acknowledgments

We would like to thank Carl B. Watt for his work in electron microscopy, imaging, and manuscript review. William Drew Ferrell was invaluable in data preparation and in reviewing the manuscript. Kevin Rapp assisted with confocal microscopy, which resulted in figure construction. Maggie Shaw and Jia-Hui Yang assisted with data acquisition, tissue preparation, immunocytochemistry, and ultramicrotomy. James R. Anderson assisted in ultrastructural data assembly. Monica Vetter and Alejandra Bosco helped provide the DBA/2J mouse tissues, provided guidance, and helped to review the manuscript. Support: NIH EY015128 (RM), NIH EY02576 (RM), EYO14800 Vision Core, an unrestricted grant from Research to Prevent Blindness to the Moran Eye Center; Edward N. and Della L. Thome Memorial Foundation grant for Age-Related Macular Degeneration Research (BWJ), a Research to Prevent Blindness Career Development Award (BWJ), Moran Eye Center Tiger Team Translational Medicine Award (BWJ), Sciences Research Grant H16-sensory-001 from the Ministry of Health, Labor and Welfare, Japan (MK).

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Authors and Affiliations

  1. Department of Ophthalmology, Moran Eye Center, University of Utah, 65 Mario Capecchi Dr., Salt Lake City, UT, 84132, USA

    B. W. Jones, Y. Lin & R. E. Marc

  2. Department of Ophthalmology, Nagoya University, Graduate School of Medicine, Nagoya, Japan

    M. Kondo & H. Terasaki

  3. Department of Ophthalmology and Visual Sciences, University of Louisville, Louisville, KY, USA

    M. McCall

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  1. B. W. Jones
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  2. M. Kondo
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  3. H. Terasaki
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  4. Y. Lin
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  5. M. McCall
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  6. R. E. Marc
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Corresponding author

Correspondence to B. W. Jones.

Additional information

The content of this invited review article was presented at the ARVO-JOS joint symposium on April 15, 2010, held during the 114th Annual Meeting of the Japanese Ophthalmological Society.

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Jones, B.W., Kondo, M., Terasaki, H. et al. Retinal remodeling. Jpn J Ophthalmol 56, 289–306 (2012). https://doi.org/10.1007/s10384-012-0147-2

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  • DOI: https://doi.org/10.1007/s10384-012-0147-2

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