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Updated: Jun 9, 2026
Encapsulated Cell Technology for the Delivery of Biologics to the Mouse Eye
Published on: March 30, 2020
Recombinant membrane-targeted form of CD59 inhibits the growth of choroidal neovascular complex in mice
Nalini S Bora1, Purushottam Jha, Valeriy V Lyzogubov
1Department of Ophthalmology, Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Abstract:
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.
Insights
Recombinant membrane-targeted CD59 (rCD59-APT542) significantly inhibited choroidal neovascularization (CNV) growth and reduced CNV size in a mouse model. This therapy works by increasing apoptosis and decreasing cell proliferation via membrane attack complex (MAC) inhibition.
Area of Science:
- Ophthalmology
- Immunology
- Regenerative Medicine
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss.
- Current treatments for CNV have limitations.
- The complement system, particularly the membrane attack complex (MAC), plays a role in CNV pathogenesis.
Purpose of the Study:
- To investigate the therapeutic potential of recombinant, membrane-targeted CD59 (rCD59-APT542) in a laser-induced murine model of CNV.
- To evaluate the effect of rCD59-APT542 on CNV growth, size, and underlying mechanisms.
Main Methods:
- CNV was induced in C57BL/6 mice using laser photocoagulation.
- rCD59-APT542 was administered via intravitreal injection.
- Effects were assessed using Western blot, immunohistochemistry, total complement hemolytic assay, and analysis of CNV growth and size.
Main Results:
- Exogenously administered rCD59-APT542 was incorporated, retained, and functionally active in the RPE and choroid.
- A single intravitreal injection of rCD59-APT542 inhibited CNV growth by approximately 79% when given during CNV development.
- rCD59-APT542 significantly reduced the size of fully developed CNV, blocked MAC formation, increased apoptosis, and decreased cell proliferation within the neovascular complex.
Conclusions:
- Recombinant membrane-targeted CD59 (rCD59-APT542) effectively inhibits the growth and reduces the size of choroidal neovascularization in a laser-induced mouse model.
- The therapeutic effects are attributed to the inhibition of MAC, leading to increased apoptosis and decreased cell proliferation in the neovascular complex.
- rCD59-APT542 shows promise as a novel therapeutic agent for treating CNV.
