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Updated: Jun 3, 2026
Intravitreal Injections in the Ovine Eye
Published on: July 5, 2022
AAV5-mediated sFLT01 gene therapy arrests retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice
Jingsheng Tuo1, Ji-Jing Pang, Xiaoguang Cao
1Immunopathology Section, Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892-1857, USA.
Abstract:
To test the effects of adeno-associated virus encoding sFLT01 (AAV5.sFLT01) on the retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice, a model for age-related macular degeneration (AMD), AAV5.sFLT01 was injected into the subretinal space of the right eyes and the left eyes served as controls. Histology found no retinal toxicity due to the treatment after 3 months. The treated eyes showed lesion arrest compared with lesion progression in the left eyes by fundus monitoring monthly and histological evaluation 3 months after treatment. Retinal ultrastructure showed fewer lipofuscin and better preserved photoreceptors after the treatment. A2E, a major component of lipofuscin, was lower in the treated eyes than in the control eyes. Molecular analysis showed that AAV5.sFLT01 lowered retinal extracellular signal-regulated kinase (ERK) phosphorylation and inducible nitric oxide synthetase expression, which suggested the involvement of reactive nitrogen species in the retinal lesions of Ccl2(-/-)/Cx3cr1(-/-). We concluded that local delivery of AAV5.sFLT01 can stabilize retinal lesions in Ccl2(-/-)/Cx3cr1(-/-) mice. The findings provide further support for the potential beneficial effects of sFLT01 gene therapy for age-related macular degeneration.
Insights
Adeno-associated virus encoding sFLT01 (AAV5.sFLT01) gene therapy stabilized retinal lesions in a mouse model of age-related macular degeneration (AMD). This treatment reduced lipofuscin accumulation and preserved photoreceptors, suggesting a potential therapeutic approach for AMD.
Area of Science:
- Ophthalmology
- Gene Therapy
- Molecular Biology
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss.
- The Ccl2(-/-)/Cx3cr1(-/-) mouse model exhibits retinal lesions similar to human AMD.
- Understanding the molecular mechanisms, including reactive nitrogen species, is crucial for AMD treatment.
Purpose of the Study:
- To evaluate the efficacy of adeno-associated virus encoding sFLT01 (AAV5.sFLT01) in treating retinal lesions.
- To assess the safety and impact of AAV5.sFLT01 on retinal structure and function in an AMD mouse model.
Main Methods:
- Subretinal injection of AAV5.sFLT01 in Ccl2(-/-)/Cx3cr1(-/-) mice, with contralateral eyes as controls.
- Monthly fundus monitoring and histological evaluation at 3 months post-treatment.
- Analysis of retinal ultrastructure, lipofuscin content (A2E), and molecular markers (ERK phosphorylation, inducible nitric oxide synthetase).
Main Results:
- AAV5.sFLT01 treatment showed no retinal toxicity after 3 months.
- Lesion arrest was observed in treated eyes, contrasting with lesion progression in control eyes.
- Reduced lipofuscin and A2E, preserved photoreceptors, and decreased ERK phosphorylation and inducible nitric oxide synthetase expression were noted.
Conclusions:
- Local delivery of AAV5.sFLT01 effectively stabilizes retinal lesions in the Ccl2(-/-)/Cx3cr1(-/-) mouse model.
- sFLT01 gene therapy demonstrates potential for treating AMD by mitigating lipofuscin accumulation and preserving retinal integrity.
- The findings suggest reactive nitrogen species play a role in AMD pathogenesis and can be targeted by sFLT01 therapy.
