PMID- 34253851
OWN - NLM
STAT- MEDLINE
DCOM- 20210827
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 101
IP  - 9
DP  - 2021 Sep
TI  - Establishing the ground squirrel as a superb model for retinal ganglion cell 
      disorders and optic neuropathies.
PG  - 1289-1303
LID - 10.1038/s41374-021-00637-y [doi]
AB  - Retinal ganglion cell (RGC) death occurs after optic nerve injury due to acute 
      trauma or chronic degenerative conditions such as optic neuropathies (e.g., 
      glaucoma). Currently, there are no effective therapies to prevent permanent 
      vision loss resulting from RGC death, underlining the need for research on the 
      pathogenesis of RGC disorders. Modeling human RGC/optic nerve diseases in 
      non-human primates is ideal because of their similarity to humans, but has 
      practical limitations including high cost and ethical considerations. In 
      addition, many retinal degenerative disorders are age-related making the study in 
      primate models prohibitively slow. For these reasons, mice and rats are commonly 
      used to model RGC injuries. However, as nocturnal mammals, these rodents have 
      retinal structures that differ from primates - possessing less than one-tenth of 
      the RGCs found in the primate retina. Here we report the diurnal thirteen-lined 
      ground squirrel (TLGS) as an alternative model. Compared to other rodent models, 
      the number and distribution of RGCs in the TLGS retina are closer to primates. 
      The TLGS retina possesses ~600,000 RGCs with the highest density along the 
      equatorial retina matching the location of the highest cone density (visual 
      streak). TLGS and primate retinas also share a similar interlocking pattern 
      between RGC axons and astrocyte processes in the retina nerve fiber layer (RNFL). 
      In addition, using TLGS we establish a new partial optic nerve injury model that 
      precisely controls the extent of injury while sparing a portion of the retina as 
      an ideal internal control for investigating the pathophysiology of axon 
      degeneration and RGC death. Moreover, in vivo optical coherence tomography (OCT) 
      imaging and ex vivo microscopic examinations of the retina in optic nerve injured 
      TLGS confirm RGC loss precedes proximal axon degeneration, recapitulating human 
      pathology. Thus, the TLGS retina is an excellent model, for translational 
      research in neurodegeneration and therapeutic neuroprotection.
CI  - (c) 2021. This is a U.S. government work and not under copyright protection in the 
      U.S.; foreign copyright protection may apply.
FAU - Xiao, Xuan
AU  - Xiao X
AD  - Eye Center, Renmin Hospital, Wuhan University, Wuhan, China; National Eye 
      Institute, National Institutes of Health, Bethesda, MD, USA.
FAU - Zhao, Tantai
AU  - Zhao T
AD  - Department of Ophthalmology The Second Xiang-Ya Hospital; Central South 
      University, Changsha, China; National Institutes of Health, Bethesda, MD, USA.
FAU - Miyagishima, Kiyoharu J
AU  - Miyagishima KJ
AUID- ORCID: 0000-0002-9744-3152
AD  - Retinal Neurophysiology Section, National Eye Institute, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Chen, Shan
AU  - Chen S
AD  - Retinal Neurophysiology Section, National Eye Institute, National Institutes of 
      Health, Bethesda, MD, USA.
FAU - Li, Wei
AU  - Li W
AUID- ORCID: 0000-0002-2897-649X
AD  - Retinal Neurophysiology Section, National Eye Institute, National Institutes of 
      Health, Bethesda, MD, USA. liwei2@nei.nih.gov.
FAU - Nadal-Nicolas, Francisco M
AU  - Nadal-Nicolas FM
AUID- ORCID: 0000-0003-4121-514X
AD  - Retinal Neurophysiology Section, National Eye Institute, National Institutes of 
      Health, Bethesda, MD, USA. nadalnicolasfm@nih.gov.
LA  - eng
GR  - Z99 EY999999/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20210712
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
SB  - IM
MH  - Animals
MH  - *Disease Models, Animal
MH  - Female
MH  - Macaca mulatta
MH  - Mice
MH  - *Optic Nerve Diseases
MH  - Rats
MH  - Retina/cytology/pathology
MH  - *Retinal Diseases
MH  - *Retinal Ganglion Cells/cytology/pathology/physiology
MH  - Sciuridae/*physiology
PMC - PMC8753557
MID - NIHMS1717486
COIS- CONFLICT OF INTEREST STATEMENT The authors declare no competing or financial 
      interests.
EDAT- 2021/07/14 06:00
MHDA- 2021/08/28 06:00
PMCR- 2022/01/12
CRDT- 2021/07/13 06:20
PHST- 2021/04/02 00:00 [received]
PHST- 2021/06/21 00:00 [accepted]
PHST- 2021/06/18 00:00 [revised]
PHST- 2021/07/14 06:00 [pubmed]
PHST- 2021/08/28 06:00 [medline]
PHST- 2021/07/13 06:20 [entrez]
PHST- 2022/01/12 00:00 [pmc-release]
AID - S0023-6837(22)00588-8 [pii]
AID - 10.1038/s41374-021-00637-y [doi]
PST - ppublish
SO  - Lab Invest. 2021 Sep;101(9):1289-1303. doi: 10.1038/s41374-021-00637-y. Epub 2021 
      Jul 12.