Abstract
It has been hypothesized that synaptic pruning precedes retinal ganglion cell degeneration in glaucoma, causing early dysfunction to retinal ganglion cells. To begin to assess this, we studied the excitatory synaptic inputs to individual ganglion cells in normal mouse retinas and in retinas with ganglion cell degeneration from glaucoma (DBA/2J), or following an optic nerve crush. Excitatory synapses were labeled by AAV2-mediated transfection of ganglion cells with PSD-95-GFP. After both insults the linear density of synaptic inputs to ganglion cells decreased. In parallel, the dendritic arbors lost complexity. We did not observe any cells that had lost dendritic synaptic input while preserving a normal or near-normal morphology. Within the temporal limits of these observations, dendritic remodeling and synapse pruning thus appear to occur near-simultaneously.
Highlights
Glaucoma is a progressive neurodegenerative disease which leads to the loss of retinal ganglion cells [1]
The antibody labels the cytoskeleton of all retinal ganglion cells (RGCs) types but exhibits a relative preference for αganglion cells, the largest ganglion cells found in the mouse retina
Synapse loss is observed in neurodegenerative diseases and a complement-driven pruning of synapses on ganglion cells has been proposed in the pathogenesis of glaucoma [8, 12]
Summary
Glaucoma is a progressive neurodegenerative disease which leads to the loss of retinal ganglion cells [1]. The death of the ganglion cells occurs by apoptosis [2] and is preceded by a remodeling of the dendritic arbor, shrinking of the soma, and axonal atrophy [3]. Recent experimental evidence indicates that the overt remodeling of the dendritic arbors may be preceded by more subtle functional impairment, possibly caused by a loss of synapses on the dendrites of the ganglion cells [4]. The elimination of synapses from neuronal circuits is an important phenomenon both in developmental maturation and in pathological conditions. In a manner quite similar to their function in immunity, complement factors opsonize synaptic structures and tag them for elimination by the microglia [7,8,9]. Indicating an PLOS ONE | DOI:10.1371/journal.pone.0144341 December 4, 2015
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