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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.
Oncogene
|December 8, 2019
Summary
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.
