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Optimization of murine retinal mitochondrial injury model
Xiaopeng Zhou1, Gengjing Fang1, Liping Zhang1
1The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, The State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Optometry and Ophthalmology, Wenzhou Medical University, Wenzhou 325000, China.
Methodsx
|May 2, 2022
Summary
This study optimized a mouse model for retinal mitochondrial injury using carbonylcyanide m-chlorophenyl hydrazine (CCCP). The A2A receptor antagonist KW6002 showed protective effects, particularly at higher CCCP doses.
Area of Science:
- Ophthalmology
- Neuroscience
- Mitochondrial Biology
Background:
- The carbonylcyanide m-chlorophenyl hydrazine (CCCP) model for retinal mitochondrial injury is established in rats but not mice.
- CCCP is known to induce Opa1 cleavage and ERK phosphorylation in cellular and rat retinal models.
Purpose of the Study:
- To establish and optimize conditions for a murine retinal mitochondrial injury model using CCCP.
- To investigate the effects of CCCP on retinal ganglion cells, retinal thickness, and related molecular markers.
- To evaluate the protective potential of the A2A receptor antagonist KW6002 in this murine model.
Main Methods:
- Intravitreal injection of varying CCCP doses (0-15 μg) in mice to establish an injury model.
- Measurement of phosphorylated ERK (p-Erk) and long/short isoforms of Opa1 (L/S-Opa1) post-injury.
- Administration of A2A receptor antagonist KW6002 before CCCP to assess its protective effects.
Main Results:
- CCCP induced dose-dependent changes in L/S-Opa1 and p-Erk levels.
- A 10 μg CCCP dose induced retinal ganglion cell apoptosis and decreased retinal thickness, with KW6002 inhibiting apoptosis but not thickness.
- A 15 μg CCCP dose induced retinal injury, with KW6002 inhibiting apoptosis and increasing retinal thickness, suggesting a dose-dependent protective effect.
Conclusions:
- Optimized conditions for a murine retinal mitochondrial injury model using CCCP were established.
- The A2A receptor antagonist KW6002 demonstrates a dose-dependent protective effect against CCCP-induced retinal injury, primarily by inhibiting apoptosis.
- The 15 μg CCCP dose is suitable for studying the therapeutic potential of A2A receptor antagonists in retinal injury.
