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Updated: Aug 2, 2025
Assessment of Vascular Regeneration in the CNS Using the Mouse Retina
Published on: June 23, 2014
Triciribine attenuates pathological neovascularization and vascular permeability in a mouse model of proliferative
Shengshuai Shan1, Fang Liu1, Edith Ford2
1Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA, 30912, USA; Research Department, Charlie Norwood VA Medical Center, Augusta, GA, 30901, USA; Vascular Biology Center, Augusta University, Augusta, GA, 30912, USA; Culver Vision Discovery Institute, Augusta University, Augusta, GA, 30912, USA.
Abstract:
Proliferative retinopathies are the leading cause of irreversible blindness in all ages, and there is a critical need to identify novel therapies. We investigated the impact of triciribine (TCBN), a tricyclic nucleoside analog and a weak Akt inhibitor, on retinal neurovascular injury, vascular permeability, and inflammation in oxygen-induced retinopathy (OIR). Post-natal day 7 (P7) mouse pups were subjected to OIR, and treated (i.p.) with TCBN or vehicle from P14-P16 and compared with age-matched, normoxic, vehicle or TCBN-treated controls. P17 retinas were processed for flat mounts, immunostaining, Western blotting, and qRT-PCR studies. Fluorescein angiography, electroretinography, and spectral domain optical coherence tomography were performed on days P21, P26, and P30, respectively. TCBN treatment significantly reduced pathological neovascularization, vaso-obliteration, and inflammation marked by reduced TNFα, IL6, MCP-1, Iba1, and F4/80 (macrophage/microglia markers) expression compared to the vehicle-treated OIR mouse retinas. Pathological expression of VEGF (vascular endothelial growth factor), and claudin-5 compromised the blood-retinal barrier integrity in the OIR retinas correlating with increased vascular permeability and neovascular tuft formation, which were blunted by TCBN treatment. Of note, there were no changes in the retinal architecture or retinal cell function in response to TCBN in the normoxia or OIR mice. We conclude that TCBN protects against pathological neovascularization, restores blood-retinal barrier homeostasis, and reduces retinal inflammation without adversely affecting the retinal structure and neuronal function in a mouse model of OIR. Our data suggest that TCBN may provide a novel therapeutic option for proliferative retinopathy.
Insights
Triciribine (TCBN) shows promise for treating proliferative retinopathies. This study found TCBN reduced retinal neovascularization and inflammation in a mouse model without harming retinal structure or function.
Area of Science:
- Ophthalmology
- Retinal Diseases
- Pharmacology
Background:
- Proliferative retinopathies cause irreversible blindness, necessitating new therapeutic strategies.
- Oxygen-induced retinopathy (OIR) is a common model for studying these conditions.
- Akt signaling pathways are implicated in retinal vascular pathologies.
Purpose of the Study:
- To evaluate the therapeutic potential of triciribine (TCBN) in a mouse model of oxygen-induced retinopathy (OIR).
- To assess TCBN's effects on retinal neurovascular injury, vascular permeability, and inflammation.
Main Methods:
- Mice were subjected to OIR and treated with TCBN or vehicle.
- Retinal tissues were analyzed using immunostaining, Western blotting, and qRT-PCR.
- Functional assessments included fluorescein angiography, electroretinography, and optical coherence tomography.
Main Results:
- TCBN significantly reduced pathological neovascularization and vaso-obliteration in OIR retinas.
- TCBN treatment decreased inflammatory markers (TNFα, IL6, MCP-1, Iba1, F4/80) and vascular endothelial growth factor (VEGF) expression.
- Blood-retinal barrier integrity was restored, and vascular permeability was reduced by TCBN.
- No adverse effects on retinal architecture or neuronal function were observed.
Conclusions:
- TCBN effectively mitigates key pathological features of OIR, including neovascularization and inflammation.
- TCBN demonstrates potential as a novel therapeutic agent for proliferative retinopathies.
- The drug preserves retinal structure and function while combating disease progression.
