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High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Toxicity and efficacy of type I interferons on the ocular surface: in vitro, animal, and clinical studies
Young In Yun1, Jung Hwa Ko2, Jin Suk Ryu2
1Laboratory of Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea; Department of Ophthalmology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea; Department of Ophthalmology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea.
Purpose:
To investigate the toxicity of type I interferons (IFNs) on the ocular surface and assess their efficacy in ocular surface tumors.
Methods:
We examined the effects of IFN-α2a, IFN-α2b and IFN-β on corneal epithelial cells and stromal fibroblasts in vitro as well as the impact of IFN-α2a on the ocular surface in mice. Additionally, we analyzed the therapeutic and adverse effects of topically administered IFN-α2a and IFN-α2b in patients with ocular surface tumors. Risk factors contributing to side effects were explored.
Results:
IFN-α2a, IFN-α2b or IFN-β reduced cell viability and induced pro-inflammatory cytokines in corneal epithelial cells and stromal fibroblasts. Furthermore, IFNs enhanced the expression of major histocompatibility complex class II and CD40 in corneal epithelial cells. In mice, subconjunctival IFN-α2a injection did not induce corneal epithelial defects or opacity, nor did it reduce aqueous tears or conjunctival goblet cells. In patients, topical IFN-α2a or IFN-α2b administration decreased tumor size and prevented recurrence; however, it was associated with mild side effects, including corneal epitheliopathy and conjunctival hyperemia. These complications were associated with longer IFN use, the presence of underlying ocular surface disease and concurrent use of mitomycin C or anti-glaucoma eye drops.
Conclusion:
Although type I IFNs cause direct toxicity on corneal cells, they do not induce significant side effects on the healthy ocular surface. Considering its therapeutic and preventive effects, topical type I IFN is safe and effective for treating ocular surface tumors. The potential for ocular side effects should be considered in eyes with identified risk factors.
Insights
Type I interferons (IFNs) show toxicity to corneal cells but are safe and effective for ocular surface tumors. Topical IFNs reduce tumor size and recurrence with manageable side effects in patients.
Area of Science:
- Ophthalmology
- Immunology
- Oncology
Background:
- Type I interferons (IFNs) are cytokines with immunomodulatory properties.
- Their potential toxicity and therapeutic applications on the ocular surface require investigation.
Purpose of the Study:
- To investigate the toxicity of type I interferons (IFNs) on the ocular surface.
- To assess the efficacy of IFNs in treating ocular surface tumors.
Main Methods:
- In vitro studies on corneal cells exposed to IFN-α2a, IFN-α2b, and IFN-β.
- In vivo studies in mice assessing IFN-α2a impact on the ocular surface.
- Clinical analysis of topical IFN-α2a and IFN-α2b in patients with ocular surface tumors, including risk factor assessment for side effects.
Main Results:
- IFNs reduced corneal cell viability and induced pro-inflammatory cytokines in vitro.
- IFNs increased MHC class II and CD40 expression on corneal epithelial cells.
- Topical IFNs decreased tumor size and recurrence in patients, with mild side effects like epitheliopathy and hyperemia, associated with longer use, underlying ocular disease, or concurrent medications.
Conclusions:
- Type I IFNs exhibit direct toxicity to corneal cells but are generally safe for the healthy ocular surface.
- Topical type I IFNs are effective and safe for treating ocular surface tumors, with a need to consider risk factors for potential side effects.
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