Cellular and circuit remodeling of the primate foveal midget pathway after acute photoreceptor loss.

Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE

Original Publication: Washington, DC : National Academy of Sciences

Retinal Cone Photoreceptor Cells*/metabolism ; Retinal Cone Photoreceptor Cells*/pathology ; Fovea Centralis* ; Retinal Bipolar Cells*/metabolism ; Retinal Bipolar Cells*/physiology ; Macaca fascicularis*; Animals ; Retinal Ganglion Cells/physiology ; Retinal Ganglion Cells/pathology ; Neuronal Plasticity/physiology ; Dendrites/physiology ; Visual Pathways ; Male

The retinal fovea in human and nonhuman primates is essential for high acuity and color vision. Within the fovea lies specialized circuitry in which signals from a single cone photoreceptor are largely conveyed to one ON and one OFF type midget bipolar cell (MBC), which in turn connect to a single ON or OFF midget ganglion cell (MGC), respectively. Restoring foveal vision requires not only photoreceptor replacement but also appropriate reconnection with surviving ON and OFF MBCs and MGCs. However, our current understanding of the effects of cone loss on the remaining foveal midget pathway is limited. We thus used serial block-face electron microscopy to determine the degree of plasticity and potential remodeling of this pathway in adult Macaca fascicularis several months after acute photoreceptor loss upon photocoagulation. We reconstructed MBC structure and connectivity within and adjacent to the region of cone loss. We found that MBC dendrites within the scotoma retracted and failed to reach surviving cones to form new connections. However, both surviving cones and ON and OFF MBC dendrites at the scotoma border exhibited remodeling, suggesting that these neurons can demonstrate plasticity and rewiring at maturity. At six months postlesion, disconnected OFF MBCs clearly lost output ribbon synapses with their postsynaptic partners, whereas the majority of ON MBCs maintained their axonal ribbon numbers, suggesting differential timing or extent in ON and OFF midget circuit remodeling after cone loss. Our findings raise rewiring considerations for cell replacement approaches in the restoration of foveal vision.
Competing Interests: Competing interests statement:The authors declare no competing interest.

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EY033447 HHS | NIH | National Eye Institute (NEI); Overseas Fellowship MEXT | Japan Society for the Promotion of Science (JSPS); P30 EY001730 United States EY NEI NIH HHS; EY01730 HHS | NIH | National Eye Institute (NEI); R21 EY033447 United States EY NEI NIH HHS; JP20bm0204002 Japan Agency for Medical Research and Development (AMED)

Keywords: foveal circuit plasticity; injury and neural circuit remodeling; retinal degeneration; retinal remodeling

Date Created: 20240904 Date Completed: 20240904 Latest Revision: 20240921

20240921

PMC11406236

10.1073/pnas.2413104121

39231211