Abstract
Purpose :
Full-length human IgG1 antibodies antagonize pathological angiogenesis independent of antigen binding, and thus may be a next-generation anti-angiogenic target for retinal disease like age-related macular degeneration and diabetic retinopathy. However, the extent to which sex influences this angioregulatory activity is unknown.
Methods :
Laser photocoagulation was performed in male and female C57BL/6J mice, followed by intravitreous injection of a full-length humanized IgG1 antibody. Choroidal neovascular volume (CNV) was measured 7 days later. Male and female derived primary macrophages BL/6J and BALB/c mice and human single donors were analyzed for VEGF-A-induced chemotaxis in the presence or absence of humanized or human IgG1 antibodies, or human IgG2 (negative control).
Results :
Human IgG1 induced a significantly greater reduction in CNV in male mice to female mice. In B6 and BALB/c macrophages, IgG1 inhibited Vegf-a induced chemotaxis to greater degree in male than female-derived cells. Similarly, primary human macrophages from male donors were significantly more sensitive to IgG1 inhibition than female donors. IgG2 treatment did not affect chemotaxis of male- or female-derived cells.
Conclusions :
The effects of IgG1 antibodies are different between male and female systems with male models being significantly more sensitive to IgG1 than females. Future studies are needed to understand the hormonal and genetic causes of these sexually dimorphic responses. These findings may support sex-specific translational application of antigen-independent antibody activities, which may ultimately result in more personalized anti-angiogenic therapies.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.