AAV Gene Augmentation of Truncated Complement Factor H Differentially Rescues Ocular Complement Dysregulation in a Mouse Model.

ABSTRACT:

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.

Methods

Using Cfh-/- mice as a model of complement dysregulation, AAV vectors expressing tCFH or FHL-1 were

SUBMITTER: Grigsby D 

PROVIDER: S-EPMC10365136 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature