Recombinant membrane-targeted form of CD59 inhibits the growth of choroidal neovascular complex in mice.
This study was designed to explore the effect of recombinant, membrane-targeted CD59 (rCD59-APT542) on the growth and size of fully developed neovascular complex using the murine model of laser-induced choroidal neovascularization (CNV). CNV was induced by laser photocoagulation in C57BL/6 mice using an argon laser, and the animals received rCD59-APT542 via intravitreal (ivt) route. Western blot analysis, immunohistochemistry, and total complement hemolytic assay demonstrated that exogenously administered rCD59-APT542 was incorporated as well as retained in RPE and choroid and was functionally active in vivo. Single ivt injection during the growth of the CNV (i.e. at day 3 post-laser) resulted in ∼79% inhibition of the further growth of neovascular complex. The size of the CNV complex was significantly (p < 0.05) reduced by the administration of rCD59-APT542 after the CNV complex has fully developed (i.e. at day 7 post-laser). Treatment with rCD59-APT542 blocked the formation of membrane attack complex (MAC), increased apoptosis and decreased cell proliferation in the neovascular complex. On the basis of results presented here we conclude that recombinant membrane targeted CD59 inhibited the growth of the CNV complex and reduced the size of fully developed CNV in the laser-induced mouse model. We propose that a combination of two mechanisms: increased apoptosis and decreased cell proliferation, both resulting from local inhibition of MAC, may be responsible for inhibition of CNV by rCD59-APT542.
Bora
Nalini S
NS
Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Jha
Purushottam
P
Lyzogubov
Valeriy V
VV
Kaliappan
Sankaranarayanan
S
Liu
Juan
J
Tytarenko
Ruslana G
RG
Fraser
Deborah A
DA
Morgan
B Paul
BP
Bora
Puran S
PS
D000818:Animals; D017209:Apoptosis; D018957:CD59 Antigens / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D020256:Choroidal Neovascularization / Q000378:metabolism*; D003165:Complement System Proteins / Q000737:chemistry; D007150:Immunohistochemistry; D007249:Inflammation; D008268:Macular Degeneration / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry*
D018957:CD59 Antigens; D011994:Recombinant Proteins; C051590:CD59 protein, human; D003165:Complement System Proteins