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Updated: Aug 30, 2025
Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
Published on: December 9, 2022
Targeting proliferative retinopathy: Arginase 1 limits vitreoretinal neovascularization and promotes angiogenic
Abdelrahman Y Fouda1,2, Zhimin Xu3,4, Jutamas Suwanpradid3,4
1University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Abstract:
Current therapies for treatment of proliferative retinopathy focus on retinal neovascularization (RNV) during advanced disease and can trigger adverse side-effects. Here, we have tested a new strategy for limiting neurovascular injury and promoting repair during early-stage disease. We have recently shown that treatment with a stable, pegylated drug form of the ureohydrolase enzyme arginase 1 (A1) provides neuroprotection in acute models of ischemia/reperfusion injury, optic nerve crush, and ischemic stroke. Now, we have determined the effects of this treatment on RNV, vascular repair, and retinal function in the mouse oxygen-induced retinopathy (OIR) model of retinopathy of prematurity (ROP). Our studies in the OIR model show that treatment with pegylated A1 (PEG-A1), inhibits pathological RNV, promotes angiogenic repair, and improves retinal function by a mechanism involving decreased expression of TNF, iNOS, and VEGF and increased expression of FGF2 and A1. We further show that A1 is expressed in myeloid cells and areas of RNV in retinal sections from mice with OIR and human diabetic retinopathy (DR) patients and in blood samples from ROP patients. Moreover, studies using knockout mice with hemizygous deletion of A1 show worsened RNV and retinal injury, supporting the protective role of A1 in limiting the OIR-induced pathology. Collectively, A1 is critically involved in reparative angiogenesis and neuroprotection in OIR. Pegylated A1 may offer a novel therapy for limiting retinal injury and promoting repair during proliferative retinopathy.
Insights
Pegylated arginase 1 (PEG-A1) effectively treats retinopathy by inhibiting abnormal blood vessel growth and promoting repair. This novel therapy offers neuroprotection and improves retinal function in early-stage disease.
Area of Science:
- Ophthalmology
- Vascular Biology
- Neuroprotection
Background:
- Current proliferative retinopathy treatments target advanced disease and cause side effects.
- Early-stage intervention is needed to limit neurovascular injury and promote repair.
- Arginase 1 (A1) has shown neuroprotective effects in various injury models.
Purpose of the Study:
- To evaluate the therapeutic potential of pegylated arginase 1 (PEG-A1) in the oxygen-induced retinopathy (OIR) model.
- To assess PEG-A1's effects on retinal neovascularization (RNV), vascular repair, and retinal function.
- To elucidate the underlying mechanisms of PEG-A1's action in retinopathy.
Main Methods:
- Treatment with PEG-A1 in the mouse OIR model.
- Assessment of RNV, vascular repair, and retinal function.
- Analysis of molecular markers (TNF, iNOS, VEGF, FGF2, A1) and A1 expression in retinal tissues and patient samples.
- Studies using A1 knockout mice.
Main Results:
- PEG-A1 treatment inhibited pathological RNV and promoted angiogenic repair.
- Retinal function was improved following PEG-A1 treatment.
- Mechanisms involved decreased TNF, iNOS, VEGF and increased FGF2, A1 expression.
- A1 was found in myeloid cells and RNV areas in OIR mice and human retinopathy samples.
- A1 deficiency exacerbated RNV and retinal injury in knockout mice.
Conclusions:
- Arginase 1 plays a critical role in reparative angiogenesis and neuroprotection in OIR.
- PEG-A1 demonstrates potential as a novel therapy for proliferative retinopathy.
- PEG-A1 may limit retinal injury and promote repair in early-stage disease.
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