Therapeutic Potential of CD55 Gene Transfer in Controlling Complement and Inflammasome Activation in Myopia
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Purpose
To investigate the relationship between transforming growth factor (TGF)-β2, complement system activation, and inflammasome pathway in myopia development.
Methods
Myopia was induced in all TGF-β isoforms, and complement activation was modulated by adeno-associated virus (AAV) vectors carrying CD55 or CD55 siRNA on Brown Norway Rats. Axial length (AXL) and refractive error were evaluated to determine the progression of myopia. Retinal tissues were analyzed using real-time quantitative PCR (qPCR), immunofluorescence staining, and western blotting to assess complement components, inflammasome markers, and signaling pathways.
Results
TGF-β2 significantly enhanced myopia progression by upregulating complement C3 and C5 while downregulating CD55, a membrane-bound complement inhibitor. This resulted in longer AXL and greater refractive errors. CD55 overexpression effectively counteracted these effects, reducing AXL elongation and suppressing inflammatory responses. Immunofluorescence and qPCR analyses confirmed lower levels of inflammasome markers interleukin (IL)-1β and NLR family pyrin domain containing 3 (NLRP3) in CD55-overexpressing eyes, indicating that CD55 can mitigate the inflammatory effects induced by TGF-β2. Conversely, inhibiting CD55 exacerbated TGF β2-induced myopia, resulting in greater AXL and higher levels of inflammatory markers. The results emphasize CD55 in modulating complement and inflammasome pathways activated by TGF-β2.
Conclusion
TGF-β2 drives myopia progression through complement and inflammasome pathways, with CD55 as a critical modulator. Targeting CD55 could offer a novel therapeutic approach for managing myopia and potentially other ocular inflammation.
Conflict of interest
No
1
Last name
TIEN
Initials of first name(s)
PT
Department
Eye Center, China Medical University Hospital
City
Taichung
Country
Taiwan
2
Last name
Wan
Initials of first name(s)
L
Department
School of Chinese Medicine, China Medical University
City
Taichung
Country
Taiwan
3
Last name
Lin
Initials of first name(s)
HJ
Department
Eye Center, China Medical University Hospital
City
Taichung
Country
Taiwan
4
Last name
Chen
Initials of first name(s)
SN
Department
Eye Center, China Medical University Hospital
City
Taichung
Country
Taiwan
5
Last name
Lin
Initials of first name(s)
CJ
Department
Eye Center, China Medical University Hospital
City
Taichung
Country
Taiwan
6
Last name
Sheu
Initials of first name(s)
SJ
Department
Department of Ophthalmology, Kaohsiung Medical University Hospital
City
Kaohsiung
Country
Taiwan
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