Daniel Grigsby, Mikael Klingeborn, Una Kelly, Lindsey A Chew, Aravind Asokan, Garth Devlin, Sharon Smith, Lisa Keyes, Adrian Timmers, Abraham Scaria, Catherine Bowes Rickman
PURPOSE: 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 aimed to untangle the role of CFH and its splice variant, factor H-like 1 (FHL-1), in ocular complement regulation derived from local versus circulating sources. We assessed the therapeutic efficacy of adeno-associated viruses (AAVs) expressing human FHL-1 and a truncated version of CFH (tCFH), which retains the functional N- and C-terminal ends of the CFH protein, in restoring the alternative complement pathway in Cfh-/- mouse eyes and plasma...
July 3, 2023: Investigative Ophthalmology & Visual Science