Complement Factor H Mutation W1206R Causes Retinal Thrombosis and Ischemic Retinopathy in Mice

Area of Science:

• Ophthalmology
• Nephrology
• Immunology

Background:

• Factor H (FH) mutations are linked to age-related macular degeneration and atypical hemolytic uremic syndrome.
• A mouse model with the FH W1206R mutation (FH^R/R) mimics human atypical hemolytic uremic syndrome.

Purpose of the Study:

• To investigate the retinal phenotype in FH^R/R mice.
• To explore the role of complement system in FH-associated retinal vascular pathology.

Main Methods:

• Retinal fluorescein angiography and optical coherence tomography imaging.
• Histologic analysis, immunofluorescence, and electron microscopy.
• Genetic knockout of C6 and pharmacologic blockade of C5.

Main Results:

• FH^R/R mice displayed retinal vascular occlusion, ischemia, leakage, edema, and degeneration.
• Complement component C6 knockout or C5 blockade prevented these retinal abnormalities.
• Vascular endothelial cell irregularity and vessel narrowing were observed.

Conclusions:

• FH^R/R mice serve as a model for retinal vascular occlusive disorders and ischemic retinopathy.
• Complement dysregulation contributes to retinal vascular occlusion.
• Anti-C5 antibody therapy may benefit C5-mediated thrombotic retinal diseases.