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Updated: Dec 8, 2025
Oxygen-Induced Retinopathy Model for Ischemic Retinal Diseases in Rodents
Published on: September 16, 2020
Acetylcholinesterase inhibition ameliorates retinal neovascularization and glial activation in oxygen-induced
Qiu-Ping Liu1, Xian Zhang1, Ya-Zhou Qin2
1Affiliated Eye Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.
Aim:
To investigate whether inhibition of acetylcholinesterase (AChE) by donepezil ameliorate aberrant retinal neovascularization (RNV) and abnormal glial activation in oxygen-induced retinopathy (OIR).
Methods:
A mouse model of RNV was induced in postnatal day 7 (P7) mice by exposure to 75% oxygen. Donepezil was administrated to P12 mice by intraperitoneal injection. Expression and localization of AChE in mouse retinas were determined by immunofluorescence. RNV was evaluated by paraffin sectioning and hematoxylin and eosin (HE) staining. Activation of retinal Müller glial cells were examined by immunoblot of glial fibrillary acidic protein (GFAP). rMC-1, a retinal Müller cell line, was used for in vitro study. Expression of hypoxia-induced factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) were determined by Western-blot analysis, enzyme-linked immunosorbent assay (ELISA) or immunostaining.
Results:
Aberrant RNV and glial activation was observed after OIR. Of note, retinal AChE was mainly expressed by retinal Müller glial cells and markedly increased in OIR mice. Systemic administration of donepezil significantly reduced RNV and abnormal glial activation in mice with OIR. Moreover, ischemia-induced HIF-1α accumulation and VEGF upregulation in OIR mouse retinas and cultured rMC-1 were significantly inhibited by donepezil intervention.
Conclusion:
AchE is implicated in RNV with OIR. Inhibition of AChE by donepeizl is likely to be a potential therapeutic approach for retinal neovascular diseases.
Insights
Donepezil inhibits acetylcholinesterase (AChE) to reduce aberrant retinal neovascularization and glial activation in oxygen-induced retinopathy. This suggests AChE inhibition is a potential therapy for retinal neovascular diseases.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Oxygen-induced retinopathy (OIR) is a model for aberrant retinal neovascularization (RNV).
- Acetylcholinesterase (AChE) is implicated in RNV, with elevated levels observed in OIR.
- Müller glial cells play a role in RNV and glial activation.
Purpose of the Study:
- To investigate the role of AChE inhibition by donepezil in ameliorating RNV and glial activation in OIR.
- To determine the effects of donepezil on hypoxia-induced factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression in the retina.
Main Methods:
- A mouse model of OIR was established by exposing P7 mice to 75% oxygen.
- Donepezil was administered intraperitoneally to P12 mice.
- Immunofluorescence, HE staining, Western-blot, and ELISA were used to assess RNV, glial activation (GFAP), AChE expression, HIF-1α, and VEGF.
Main Results:
- OIR induced aberrant RNV and Müller glial cell activation, with increased AChE expression primarily in glial cells.
- Donepezil treatment significantly reduced RNV and glial activation in OIR mice.
- Donepezil inhibited ischemia-induced HIF-1α accumulation and VEGF upregulation in OIR retinas and cultured Müller cells.
Conclusions:
- AChE is involved in the pathogenesis of RNV in OIR.
- Inhibition of AChE by donepezil demonstrates therapeutic potential for treating retinal neovascular diseases.
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