Complement C3 knockout protects photoreceptors in the sodium iodate model.

Area of Science:

• Ophthalmology
• Immunology
• Neuroscience

Background:

• Complement factor 3 (C3) is a therapeutic target for age-related macular degeneration (AMD).
• The precise location where C3 acts in AMD pathogenesis remains unclear.

Purpose of the Study:

• To investigate the protective effects of C3 knockout on photoreceptors and retinal pigment epithelial cells (RPE) in a sodium iodate (NaIO3)-induced AMD model.
• To determine the impact of C3 deficiency on retinal structure and function.

Main Methods:

• Sodium iodate (NaIO3) was administered to C3 knockout (C3-/-) and wild-type (WT) mice.
• Retinal function and structure were assessed using electroretinography and optical coherence tomography.
• Retinal C3 expression, iC3b deposition, and cell survival were analyzed via immunohistochemistry, qPCR, and ELISA.

Main Results:

• NaIO3 increased C3 levels in the neural retina but not RPE.
• C3-/- mice showed reduced iC3b deposition on photoreceptor outer segments and were protected against photoreceptor thinning.
• Partial preservation of rod and cone function was observed in C3-/- mice, while RPE structure and function remained unaffected.

Conclusions:

• Outer segment opsonization by C3 contributes to photoreceptor cell death in this AMD model.
• Targeting C3 offers a potential therapeutic strategy to protect photoreceptor structure and function during RPE stress in AMD.