title: Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision.
abstract: Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring.SIGNIFICANCE STATEMENTLoss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration.
authors.affiliation: Electrical Engineering and cbeier@ucsc.edu sashake3@ucsc.edu.
authors.forename: Corinne
authors.identifier: 0000-0002-0698-7219
authors.initials: C
authors.lastname: Beier
authors.affiliation: Santa Cruz Institute for Particle Physics, University of California, Santa Cruz, California 95064, and.
authors.forename: Anahit
authors.initials: A
authors.lastname: Hovhannisyan
authors.affiliation: Santa Cruz Institute for Particle Physics, University of California, Santa Cruz, California 95064, and.
authors.forename: Sydney
authors.identifier: 0000-0003-2298-4170
authors.initials: S
authors.lastname: Weiser
authors.affiliation: Ophthalmology and.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kung
authors.affiliation: Ophthalmology and.
authors.forename: Seungjun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Ophthalmology and.
authors.forename: Dae Yeong
authors.initials: DY
authors.lastname: Lee
authors.affiliation: Ophthalmology and.|Hansen Experimental Physics Laboratory, Stanford University, Stanford, California 94305.
authors.forename: Philip
authors.initials: P
authors.lastname: Huie
authors.affiliation: Hansen Experimental Physics Laboratory, Stanford University, Stanford, California 94305.
authors.forename: Roopa
authors.initials: R
authors.lastname: Dalal
authors.affiliation: Ophthalmology and.|Hansen Experimental Physics Laboratory, Stanford University, Stanford, California 94305.
authors.forename: Daniel
authors.initials: D
authors.lastname: Palanker
authors.affiliation: Santa Cruz Institute for Particle Physics, University of California, Santa Cruz, California 95064, and cbeier@ucsc.edu sashake3@ucsc.edu.
authors.forename: Alexander
authors.initials: A
authors.lastname: Sher
mesh_terms: D000818:Animals; D003712:Dendrites / Q000502:physiology; D003714:Denervation; D007091:Image Processing, Computer-Assisted; D009473:Neuronal Plasticity; D009475:Neurons, Afferent / Q000502:physiology; D011817:Rabbits; D051245:Retinal Bipolar Cells / Q000502:physiology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D014785:Vision, Ocular / Q000502:physiology*; D014795:Visual Pathways
keywords: dendrite restructuring; photoreceptor; plasticity; retina; retinal bipolar cell; synapse formation