CREG Protects Retinal Ganglion Cells loss and Retinal Function Impairment Against ischemia-reperfusion Injury in mice via Akt Signaling Pathway

Abstract

PurposeThe 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 ischemiareperfusion 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. MethodsWe 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 immuno uorescence staining and western blotting. RGCs survival was assessed by immuno uorescence staining of at-mounted retinas. Retinal apoptosis was measured by the staining of TdT-mediated dUTP nick-end labeling and cleaved caspase-3. Electroretinogram analysis and optomotor response (ERG) 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. ResultsWe found that CREG expression was decreased after RIRI, and intravitreal injection of CREG attenuated RGCs loss and retinal apoptosis. Besides, there was a signi cant recovery of the ERG a-and b-wave amplitudes and visual function after treatment with CERG. Furthermore, intravitreal injection of CREG upregulated p-Akt and Bcl-2 expression and downregulated Bax expression. ConclusionOur 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.

Minocycline Administration Does Not Have an Effect on Retinal Ganglion Cell Survival in a Murine Model of Ocular Hypertension

“…Furthermore, TUNEL staining is a marker of late apoptosis, compared to the activation of Casp3 that marks the early stages of apoptosis [63]. a-Casp3 upregulation is a common early event observed in several RGC degeneration models, such as retinal organotypic cultures [24], ischemia-reperfusion [64] or ONT or ONC [13,26,37,65]. Therefore, neuroprotective therapies for RGC rescue will most likely need to be administered early after the insult, well before loss of Brn3a expression in the RGC population.…”