Complement depletion with humanized cobra venom factor in a mouse model of age-related macular degeneration.
The effect of complement depletion with humanized cobra venom factor (CVF) on retinal lesion development/neovascularization was determined in a mouse model of wet age-related macular degeneration (AMD). Mice were treated with the humanized CVF protein HC3-1496 prior to, and once daily for 28 days after laser coagulation surgery of the retina. CVF transgenic mice exhibiting permanently low levels of serum complement activity and PBS-treated mice served as positive and negative controls, respectively. Fluorescein isothiocyanate (FITC)-dextran funduscopy after laser surgery indicated the presence of lesions in all mice that underwent laser surgery. In HC3-1496-treated mice as well as CVF transgenic mice smaller lesions were seen after 8 days. Measurement of lesion sizes by histopathological examination of eyes after 28 days revealed a significant reduction of lesion area and volume in both HC3-1496-treated animals and CVF transgenic animals compared to PBS-treated control animals. Systemic complement depletion with a complement depletor, such as the humanized CVF protein HC3-1496, represents a promising therapeutic concept for patients with wet AMD.
Fritzinger
David C
DC
Cancer Research Center of Hawaii, University of Hawaii at Manoa, Honolulu, HI 96813, USA. dfritzin@crch.hawaii.edu
Dean
Robin
R
Meschter
Carol
C
Wong
Katina
K
Halter
Roman
R
Borlak
Jürgen
J
St John
William D
WD
Vogel
Carl-Wilhelm
CW
D000818:Animals; D003176:Complement C3 / Q000235:genetics; D051056:Complement Inactivating Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000235:genetics; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000601:surgery
D003176:Complement C3; D051056:Complement Inactivating Agents; D004546:Elapid Venoms; D011993:Recombinant Fusion Proteins; C016310:cobra venom factor