TY - JOUR
T1 - Subtype-specific response of retinal ganglion cells to optic nerve crush
AU - Daniel, S.
AU - Clark, Af
AU - McDowell, Cm
N1 - Funding Information:
We would like to thank Dr. Andrew Huberman (Stanford University) for TRHR-GFP mice and MMRRCs for CDH3-GFP and CB2-GFP mice. This work was supported by University of North Texas Health Science Center seed grant and a grant from the Glaucoma Research Foundation.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Glaucoma is a neurodegenerative disease with retinal ganglion cell (RGC) loss, optic nerve degeneration and subsequent vision loss. There are about 30 different subtypes of RGCs whose response to glaucomatous injury is not well characterized. The purpose of this study was to evaluate the response of 4 RGC subtypes in a mouse model of optic nerve crush (ONC). In this study, we also evaluated the pattern of axonal degeneration in RGC subtypes after nerve injury. We found that out of the 4 subtypes, transient-Off α RGCs are the most susceptible to injury followed by On–Off direction selective RGCs (DSGC). Non-image forming RGCs are more resilient with ipRGCs exhibiting the most resistance of them all. In contrast, axons degenerate irrespective of their retinal soma after ONC injury. In conclusion, we show that RGCs have subtype specific cell death response to ONC injury and that RGC axons disintegrate in an autonomous fashion undergoing Wallerian degeneration. These discoveries can further direct us towards effective diagnostic and therapeutic approaches to treat optic neuropathies, such as glaucoma.
AB - Glaucoma is a neurodegenerative disease with retinal ganglion cell (RGC) loss, optic nerve degeneration and subsequent vision loss. There are about 30 different subtypes of RGCs whose response to glaucomatous injury is not well characterized. The purpose of this study was to evaluate the response of 4 RGC subtypes in a mouse model of optic nerve crush (ONC). In this study, we also evaluated the pattern of axonal degeneration in RGC subtypes after nerve injury. We found that out of the 4 subtypes, transient-Off α RGCs are the most susceptible to injury followed by On–Off direction selective RGCs (DSGC). Non-image forming RGCs are more resilient with ipRGCs exhibiting the most resistance of them all. In contrast, axons degenerate irrespective of their retinal soma after ONC injury. In conclusion, we show that RGCs have subtype specific cell death response to ONC injury and that RGC axons disintegrate in an autonomous fashion undergoing Wallerian degeneration. These discoveries can further direct us towards effective diagnostic and therapeutic approaches to treat optic neuropathies, such as glaucoma.
UR - http://www.scopus.com/inward/record.url?scp=85062238168&partnerID=8YFLogxK
U2 - 10.1038/s41420-018-0069-y
DO - 10.1038/s41420-018-0069-y
M3 - Article
AN - SCOPUS:85062238168
SN - 2058-7716
VL - 4
JO - Cell Death Discovery
JF - Cell Death Discovery
IS - 1
M1 - 67
ER -