The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic.
O'Leary. Olivia E OE; Canning. Paul P; Reid. Emma E; Bertelli. Pietro M PM; McKeown. Stuart S; Brines. Michael M; Cerami. Anthony A; Du. Xuan X; Xu. Heping H; Chen. Mei M; Dutton. Louise L; Brazil. Derek P DP; Medina. Reinhold J RJ; Stitt. Alan W AW
Key Findings
- ARA‑290 activates survival signaling and improves the viability of endothelial colony‑forming cells (ECFCs) under oxidative stress in vitro.
- Systemic ARA‑290 reduces pro‑inflammatory cytokines (IL‑1β and TNF‑α) in the retinas of mice with oxygen‑induced retinopathy.
- When ECFCs are transplanted into the damaged retina, their ability to restore blood vessels is enhanced by ARA‑290 but not by regular erythropoietin (EPO).
Practical Outcomes
- ARA‑290 shows promise as an anti‑inflammatory agent that could boost cell‑based therapies for retinal diseases, but it is not yet a stand‑alone treatment for humans. For biohackers, the main takeaway is that this peptide may have broader tissue‑protective effects, yet more clinical research is needed before safe dosing or self‑administration can be recommended.
Summary
In a mouse model of eye disease caused by poor blood flow, the peptide ARA‑290 (cibinetide) helped calm inflammation and protected blood‑vessel cells from damage. When the peptide was given together with a type of stem‑cell therapy, the cells repaired the damaged retina better than without the peptide. However, the study was done in animals and used a cell‑transplant approach, so it doesn’t give a ready‑to‑use protocol for people.
Abstract
Retinal ischemia remains a common sight threatening end-point in blinding diseases such as diabetic retinopathy and retinopathy of prematurity. Endothelial colony forming cells (ECFCs) represent a subpopulation of endothelial progenitors with therapeutic utility for promoting reparative angiogenesis in the ischaemic retina. The current study has investigated the potential of enhancing this cell therapy approach by the dampening of the pro-inflammatory milieu typical of ischemic retina. Based on recent findings that ARA290 (cibinetide), a peptide based on the Helix-B domain of erythropoietin (EPO), is anti-inflammatory and tissue-protective, the effect of this peptide on ECFC-mediated vascular regeneration was studied in the ischemic retina. The effects of ARA290 on pro-survival signaling and function were assessed in ECFC cultures in vitro. Efficacy of ECFC transplantation therapy to promote retinal vascular repair in the presence and absence of ARA290 was studied in the oxygen induced retinopathy (OIR) model of retinal ischemia. The inflammatory cytokine profile and microglial activation were studied as readouts of inflammation. ARA290 activated pro-survival signaling and enhanced cell viability in response to H<sub>2</sub>O<sub>2</sub>-mediated oxidative stress in ECFCs in vitro. Preconditioning of ECFCs with EPO or ARA290 prior to delivery to the ischemic retina did not enhance vasoreparative function. ARA290 delivered systemically to OIR mice reduced pro-inflammatory expression of IL-1β and TNF-α in the mouse retina. Following intravitreal transplantation, ECFCs incorporated into the damaged retinal vasculature and significantly reduced avascular area. The vasoreparative function of ECFCs was enhanced in the presence of ARA290 but not EPO. Regulation of the pro-inflammatory milieu of the ischemic retina can be enhanced by ARA290 and may be a useful adjunct to ECFC-based cell therapy for ischemic retinopathies.
Study Information
pubmed
2019
2019-03-12T00:00:00.000Z
10.1016/j.exer.2019.03.001
17
72