• This review of previously published literature evaluates the processes and mechanisms of retinal remodeling and the potential methods for halting this very damaging phenomenon.

    Retinal remodeling as a consequence of retinal degenerative disease is unavoidable. Numerous studies have explored neural retinal remodeling, as well as the therapeutic implications of retinal degenerations.

    The consensus is that the neural retina becomes reactive and is not passive in the face of photoreceptor degenerations. Furthermore, the substantial alterations now recognized as retinal remodeling occur from the molecular level up through the synaptic, cellular and tissue levels, to involve not only photoreceptors but all of the cell populations in the neural retina.

    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, a number of potential opportunities for intervention are revealed through the study of retinal remodeling, including therapies designed to slow down photoreceptor loss and limit or arrest remodeling events, and optogenetic approaches that target appropriate classes of neurons in the remnant neural retina.

    The spectrum of diseases in humans that include retinal degeneration and subsequent remodeling is broader than widely considered. Studies show that animal models of retinitis pigmentosa demonstrate and duplicate features of human retinal degeneration and remodeling.

    The authors believe there is a way forward using approaches pioneered in the optogenetics community that utilize existing, remnant cell populations with intervention prior to large-scale restructuring of the retina. These approaches could conceivably be used as a relatively late intervention when patients have lost functional photoreceptors.