TY - JOUR
T1 - A controlled impact of optic nerve as a new model of traumatic optic neuropathy in Mouse
AU - Ibrahim, Ahmed S.
AU - Elmasry, Khaled
AU - Wan, Ming
AU - Abdulmoneim, Samer
AU - Still, Amber
AU - Khan, Farid
AU - Khalil, Abraham
AU - Saul, Alan
AU - Hoda, Md Nasrul
AU - Al-Shabrawey, Mohamed
N1 - Publisher Copyright:
© 2018 The Authors.
PY - 2018/11
Y1 - 2018/11
N2 - PURPOSE. Traumatic optic neuropathy (TON) is the most feared visual consequence of head and ocular trauma in both military and civilian communities, for which standard treatment does not exist. Animal models are critical for the development of novel TON therapies as well as the understanding of TON pathophysiology. However, the models currently used for TON have some limitations regarding consistency and mirroring the exact pathological progression of TON in closed ocular trauma. In this study, we modified the model of controlled cortical impact and adapted it for studying TON. METHODS. We defined new standardized procedures to induce TON in mice, wherein the optic nerve is reproducibly exposed to a graded controlled impact of known velocity to produce a graded deficit in retinal ganglion cell (RGC) electrophysiological functions. RESULTS. The key results of validating this newly modified model, ‘‘controlled orbital impact (COI),’’ included (1) the injury parameters (velocity as well as contusion depth and time), which were quantifiable and manageable to generate a wide range of TON severities; (2) a reproducible endpoint of diminished positive scotopic threshold response (pSTR) has been achieved without the interference of surgical variability and destruction of surrounding tissues; (3) the contralateral eyes showed no significant difference to the eyes of naïve mice, allowing them to be used as an internal control to minimize interindividual variability among mice; and (4) the occurrence of injury-associated mortality and/or ocular comorbidity was rare. CONCLUSIONS. Taken together, this model overcomes some limitations of prior TON mouse models and provides an innovative platform to identify therapeutic targets for neuroprotection and/or neurorestoration following traumatic ocular injury.
AB - PURPOSE. Traumatic optic neuropathy (TON) is the most feared visual consequence of head and ocular trauma in both military and civilian communities, for which standard treatment does not exist. Animal models are critical for the development of novel TON therapies as well as the understanding of TON pathophysiology. However, the models currently used for TON have some limitations regarding consistency and mirroring the exact pathological progression of TON in closed ocular trauma. In this study, we modified the model of controlled cortical impact and adapted it for studying TON. METHODS. We defined new standardized procedures to induce TON in mice, wherein the optic nerve is reproducibly exposed to a graded controlled impact of known velocity to produce a graded deficit in retinal ganglion cell (RGC) electrophysiological functions. RESULTS. The key results of validating this newly modified model, ‘‘controlled orbital impact (COI),’’ included (1) the injury parameters (velocity as well as contusion depth and time), which were quantifiable and manageable to generate a wide range of TON severities; (2) a reproducible endpoint of diminished positive scotopic threshold response (pSTR) has been achieved without the interference of surgical variability and destruction of surrounding tissues; (3) the contralateral eyes showed no significant difference to the eyes of naïve mice, allowing them to be used as an internal control to minimize interindividual variability among mice; and (4) the occurrence of injury-associated mortality and/or ocular comorbidity was rare. CONCLUSIONS. Taken together, this model overcomes some limitations of prior TON mouse models and provides an innovative platform to identify therapeutic targets for neuroprotection and/or neurorestoration following traumatic ocular injury.
KW - Controlled impact
KW - Microglia
KW - PSTR
KW - Retinal ganglion cell (RGC)
KW - Scotopic threshold response
KW - TON
KW - Traumatic optic neuropathy
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U2 - 10.1167/iovs.18-24773
DO - 10.1167/iovs.18-24773
M3 - Article
C2 - 30480743
AN - SCOPUS:85057269425
SN - 0146-0404
VL - 59
SP - 5548
EP - 5557
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 13
ER -