Catherine Bowes Rickman, PhD

Speaker

Catherine Bowes Rickman, PhD
George and Geneva Boguslavsky Professor of Ophthalmology
Professor of Cell Biology
Duke University Medical Center
Host: John Flannery

Date and Time

Monday, March 13, 2023
11:10 am - 12:30 pm

Location

Room 489 Minor Hall

Catherine Bowes Rickman's Abstract

Re-thinking complement-based therapies for Age-related macular degeneration.

Complement dysregulation in the eye has been implicated in the pathogenesis of age-related macular degeneration (AMD) and genetic variants of complement factor H (CFH) are strongly associated with AMD risk. We therefore aim to untangle the role of the complement regulator, CFH, and its splice variant, factor H-like 1 (FHL-1), in regulation of complement in the eye from local versus circulating sources. We assessed the therapeutic efficacy of adeno-associated viruses (AAVs) expressing human FHL-1 and truncated versions of CFH, which retain the functional N- and C-terminal ends of the CFH protein, in restoring the alternative complement pathway in Cfh-/- mouse eyes and plasma. Our findings demonstrate that the C-terminus of human CFH is necessary for regulation of complement in the murine eye. Additionally, exogenous CFH must be synthesized locally for maximal complement regulation in the retina, laying the foundation for developing CFH augmentation gene therapies for the eye.