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Updated: Jul 24, 2025
A Mouse Model of Retinal Ischemia-Reperfusion Injury Through Elevation of Intraocular Pressure
Published on: July 14, 2016
CREG Protects Retinal Ganglion Cells loss and Retinal Function Impairment Against ischemia-reperfusion Injury in mice
Siyu Zeng1, Lei Du1, Guojing Lu1
1Eye Center, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, 430060, Hubei Province, People's Republic of China.
Purpose:
The irreversible death of retinal ganglion cells (RGCs) plays an important role in the pathogenesis of glaucoma. Cellular repressor of E1A-stimulated genes (CREG), a secreted glycoprotein involved in cellular proliferation and differentiation, has been shown to protect against myocardial and renal ischemia-reperfusion damage. However, the role of CREG in retinal ischemia-reperfusion injury (RIRI) remains unknown. In this study, we aimed to explore the effect of CREG on RGCs apoptosis after RIRI.
Methods:
We used male C57BL/6J mice to establish the RIRI model. Recombinant CREG was injected at 1 day before RIRI. The expression and distribution of CREG were examined by immunofluorescence staining and western blotting. RGCs survival was assessed by immunofluorescence staining of flat-mounted retinas. Retinal apoptosis was measured by the staining of TdT-mediated dUTP nick-end labeling and cleaved caspase-3. Electroretinogram (ERG) analysis and optomotor response were conducted to evaluate retinal function and visual acuity. The expressions of Akt, phospho-Akt (p-Akt), Bax, and Bcl-2 were analyzed by western blotting to determine the signaling pathways of CREG.
Results:
We found that CREG expression was decreased after RIRI, and intravitreal injection of CREG attenuated RGCs loss and retinal apoptosis. Besides, the amplitudes of a-wave, b-wave, and photopic negative response (PhNR) in ERG, as well as visual function, were significantly restored after treatment with CERG. Furthermore, intravitreal injection of CREG upregulated p-Akt and Bcl-2 expression and downregulated Bax expression.
Conclusion:
Our results demonstrated that CREG protected RGCs from RIRI and alleviated retinal apoptosis by activating Akt signaling. In addition, CREG also improved retinal function and visual acuity.
Insights
Cellular repressor of E1A-stimulated genes (CREG) protects retinal ganglion cells (RGCs) from injury. CREG treatment reduced RGCs apoptosis and improved visual function in a mouse model of retinal ischemia-reperfusion injury (RIRI).
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Glaucoma pathogenesis involves retinal ganglion cell (RGC) death.
- Cellular repressor of E1A-stimulated genes (CREG) protects against ischemia-reperfusion injury in other organs.
- The role of CREG in retinal ischemia-reperfusion injury (RIRI) is currently unknown.
Purpose of the Study:
- To investigate the effect of CREG on RGC apoptosis following RIRI.
- To explore the potential therapeutic role of CREG in RIRI.
Main Methods:
- A mouse model of RIRI was established.
- Recombinant CREG was administered intravitreally.
- RGC survival, apoptosis, retinal function (ERG, optomotor response), and signaling pathways (Akt, Bax, Bcl-2) were assessed.
Main Results:
- CREG expression decreased after RIRI.
- CREG treatment attenuated RGC loss and retinal apoptosis.
- CREG administration restored retinal function and visual acuity.
- CREG upregulated pro-survival Akt signaling (p-Akt, Bcl-2) and downregulated pro-apoptotic Bax.
Conclusions:
- CREG protects RGCs from RIRI-induced apoptosis.
- CREG alleviates RIRI by activating the Akt signaling pathway.
- CREG treatment improves retinal function and visual acuity in RIRI.
