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Effects of intravitreally injected Fc fragment on rat eyes
Tatjana Taubitz1, Laura-Pia Steinbrenner1, Alexander V Tschulakow1
1Centre for Ophthalmology, Division of Experimental Vitreoretinal Surgery, Schleichstrasse 12/1, Tuebingen, Germany.
Purpose:
Anti-vascular endothelial growth factor (VEGF) drugs are used to treat neovascular eye diseases. Some of these drugs contain Fc fragments (Fc), but it is unknown how their mode of action is influenced by Fc. Therefore, this study investigated the effects of Fc on rat eyes after intravitreal injection.
Methods:
Eighteen Long-Evans rats were intravitreally injected with sterile, biotin-labeled rat Fc (9.1 μg in 5 μl PBS). For control, 5 μl PBS was injected in another nine rats. Animals were sacrificed between 1 and 3 days (group 1), 7 days (group 2), and 14 days (group 3) after injection. The right eyes were examined by electron microscopy (EM). The left eyes were stained by immunohistochemistry to investigate the distribution of Fc and the presence of macrophages.
Results:
After 1 day, Fc had penetrated into the anterior chamber and the retina up to the inner nuclear layer, and was located especially in retinal vessels. High numbers of infiltrating cells were present within the vitreous, around the ciliary body, anterior chamber and inside the retina 1-3 days after Fc injection (p < 0.02 group 1 vs. control). Immunohistochemistry and EM showed that they were macrophages or granulocytes in close association with Fc. Ultrastructurally, there were effects on the blood vessels such as thrombocyte activation and fibrin formation.
Conclusions:
Biotin labeling is ideal for investigating the distribution of intravitreally injected proteins in ocular tissue. Fc fragments at a dose corresponding to their concentration in standard AMD treatments induced inflammation, and particularly the attraction of immune-competent cells. This may be associated with the risk of inflammation or endophthalmitis after anti-VEGF treatment, and needs further investigation.
Insights
Intravitreal injection of Fc fragments in rat eyes induced inflammation and attracted immune cells, potentially increasing risks associated with anti-VEGF treatments for neovascular eye diseases.
Area of Science:
- Ophthalmology
- Immunology
- Vascular Biology
Background:
- Anti-vascular endothelial growth factor (VEGF) therapies are crucial for treating neovascular eye diseases.
- Some anti-VEGF drugs incorporate Fc fragments, but their specific role and impact on ocular tissue remain unclear.
- Understanding the influence of Fc fragments is essential for optimizing anti-VEGF treatment safety and efficacy.
Purpose of the Study:
- To investigate the effects of Fc fragments on rat eyes following intravitreal injection.
- To determine the distribution and ocular tissue interactions of Fc fragments.
- To assess the inflammatory response induced by Fc fragments in the eye.
Main Methods:
- Intravitreal injection of biotin-labeled rat Fc or PBS (control) into Long-Evans rats.
- Ocular tissue examination using electron microscopy (EM) and immunohistochemistry at 1-3, 7, and 14 days post-injection.
- Analysis of Fc distribution, presence of macrophages, and vascular effects.
Main Results:
- Fc fragments distributed within the anterior chamber and retina, localizing in retinal vessels.
- Significant infiltration of macrophages and granulocytes into ocular tissues observed 1-3 days post-Fc injection.
- Ultrastructural evidence of vascular effects, including thrombocyte activation and fibrin formation.
Conclusions:
- Biotin labeling is effective for tracking intravitreally injected proteins in ocular tissues.
- Fc fragments, at concentrations relevant to AMD treatments, trigger ocular inflammation and immune cell attraction.
- These findings suggest a potential link between Fc fragments and the risk of inflammation or endophthalmitis in anti-VEGF therapy, warranting further research.
