TY - JOUR
T1 - Characterization of non-alpha retinal ganglion cell injury responses reveals a possible block to restoring ipRGC function
AU - Hunyara, John L.
AU - Foshe, Sierra
AU - Varadarajan, Supraja G.
AU - Gribble, Katherine D.
AU - Huberman, Andrew D.
AU - Kolodkin, Alex L.
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/11
Y1 - 2022/11
N2 - Visual impairment caused by retinal ganglion cell (RGC) axon damage or degeneration affects millions of individuals throughout the world. While some progress has been made in promoting long-distance RGC axon regrowth following injury, it remains unclear whether RGC axons can properly reconnect with their central targets to restore visual function. Additionally, the regenerative capacity of many RGC subtypes remains unknown in part due to a lack of available genetic tools. Here, we use a new mouse line, Sema6ACreERT2, that labels On direction-selective RGCs (oDSGCs) and characterize the survival and regenerative potential of these cells following optic nerve crush (ONC). In parallel, we use a previously characterized mouse line, Opn4CreERT2, to answer these same questions for M1 intrinsically photosensitive RGCs (ipRGCs). We find that both M1 ipRGCs and oDSGCs are resilient to injury but do not display long-distance axon regrowth following Lin28a overexpression. Unexpectedly, we found that M1 ipRGC, but not oDSGC, intraretinal axons exhibit ectopic branching and are misaligned near the optic disc between one- and three-weeks following injury. Additionally, we observe that numerous ectopic presynaptic specializations associate with misguided ipRGC intraretinal axons. Taken together, these results reveal insights into the injury response of M1 ipRGCs and oDSGCs, providing a foundation for future efforts seeking to restore visual system function following injury.
AB - Visual impairment caused by retinal ganglion cell (RGC) axon damage or degeneration affects millions of individuals throughout the world. While some progress has been made in promoting long-distance RGC axon regrowth following injury, it remains unclear whether RGC axons can properly reconnect with their central targets to restore visual function. Additionally, the regenerative capacity of many RGC subtypes remains unknown in part due to a lack of available genetic tools. Here, we use a new mouse line, Sema6ACreERT2, that labels On direction-selective RGCs (oDSGCs) and characterize the survival and regenerative potential of these cells following optic nerve crush (ONC). In parallel, we use a previously characterized mouse line, Opn4CreERT2, to answer these same questions for M1 intrinsically photosensitive RGCs (ipRGCs). We find that both M1 ipRGCs and oDSGCs are resilient to injury but do not display long-distance axon regrowth following Lin28a overexpression. Unexpectedly, we found that M1 ipRGC, but not oDSGC, intraretinal axons exhibit ectopic branching and are misaligned near the optic disc between one- and three-weeks following injury. Additionally, we observe that numerous ectopic presynaptic specializations associate with misguided ipRGC intraretinal axons. Taken together, these results reveal insights into the injury response of M1 ipRGCs and oDSGCs, providing a foundation for future efforts seeking to restore visual system function following injury.
KW - Axon regeneration
KW - Intraretinal axons
KW - Lin28
KW - On DSGCs
KW - Retinal ganglion cells
KW - ipRGCs
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U2 - 10.1016/j.expneurol.2022.114176
DO - 10.1016/j.expneurol.2022.114176
M3 - Article
C2 - 35870522
AN - SCOPUS:85135135126
SN - 0014-4886
VL - 357
JO - Experimental Neurology
JF - Experimental Neurology
M1 - 114176
ER -