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Blue light-triggered optogenetic system for treating uveal melanoma
Mingliang Zhang1, Xiao Lin1, Jinping Zhang1
1Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, 251 Fukang Road, Tianjin, 300384, China.
Abstract:
Uveal melanoma is the most common intraocular primary malignancy in adults and has been considered a fatal disease for decades. Optogenetics is an emerging technique that can control the activation of signaling components via irradiation with visible light. The clinical translation of optogenetics has been limited because of the need for surgical implantation of electrodes and relatively shallow tissue penetration. As visible light easily penetrates the eyes, we hypothesized that an optogenetics approach can be an effective treatment of uveal melanoma without surgery. In this study, we evaluated the feasibility of this strategy by using a genetically encoded optogenetic system based on reversible blue light-induced binding pairs between Fas-CIB1-EGFP and CRY2-mCherry-FADD. Subretinal injection of B16 cells was performed to create a uveal melanoma model. Plasmids pairs were co-transfected into B16 cells. We found that blue light irradiation dynamically controlled the translocation of FADD to Fas on the plasma membrane and induced the apoptosis of B16 cells transfected with the optogenetic nanosystem in vitro. Moreover, the blue light-controlled optogenetic nanosystem suppressed the growth of uveal melanoma in vivo by inducing apoptosis. These results suggest that light-controlled optogenetic therapy can be used as a potential novel therapeutic strategy for uveal melanoma.
Insights
This study demonstrates a novel, non-surgical optogenetic therapy for uveal melanoma. Blue light effectively triggered apoptosis in cancer cells, offering a potential new treatment for this eye cancer.
Area of Science:
- Ophthalmology
- Genetics
- Biotechnology
Background:
- Uveal melanoma is the most common adult intraocular malignancy, historically associated with poor prognosis.
- Optogenetics offers light-controlled cellular manipulation but faces clinical translation challenges due to surgical requirements and limited light penetration.
- The eye's transparency to visible light presents a unique opportunity for non-invasive optogenetic therapies.
Purpose of the Study:
- To evaluate the feasibility of a non-surgical, light-based optogenetic therapy for uveal melanoma.
- To investigate the use of a reversible blue light-induced binding system for controlling apoptosis in uveal melanoma cells.
- To establish a potential novel therapeutic strategy for uveal melanoma using optogenetics.
Main Methods:
- Developed a genetically encoded optogenetic system utilizing reversible blue light-induced binding pairs (Fas-CIB1-EGFP and CRY2-mCherry-FADD).
- Established a uveal melanoma model by subretinal injection of B16 cells in vivo.
- Co-transfected B16 cells with the optogenetic system plasmids and assessed apoptosis induction via blue light irradiation.
Main Results:
- Blue light irradiation dynamically controlled the translocation of FADD to Fas on the plasma membrane in transfected B16 cells.
- The optogenetic nanosystem induced apoptosis in B16 cells in vitro upon blue light exposure.
- In vivo, blue light-controlled optogenetic therapy suppressed uveal melanoma growth by inducing apoptosis.
Conclusions:
- A non-surgical, light-controlled optogenetic nanosystem effectively induces apoptosis in uveal melanoma cells.
- This strategy demonstrates the potential for treating uveal melanoma without invasive surgical procedures.
- Optogenetic therapy represents a promising novel therapeutic avenue for uveal melanoma.
