CTLA-2 Alpha Is a Potent Inhibitor of Angiogenesis in Murine Ocular Tissue.

Kazuichi Maruyama,Christoph Peters,Yoshimi Yamamoto,Kohji Nishida,Sunao Sugita,Yasuo Uchiyama,Masato Koike,Kazuhito Yoneda

doi:10.3390/antiox10030456

Abstract

Cytotoxic T lymphocyte antigen-2 (CTLA-2) alpha has been reported to suppress the activities of cathepsin L (Cath L), which is deeply involved in angiogenesis. Therefore, we assessed whether CTLA-2 alpha plays a role in angiogenesis in ocular tissue. To establish models of corneal inflammation and experimental choroidal neovascularization (CNV), male C57BL/6J mice (n = 5) underwent corneal suture placement or laser-induced CNV, respectively. Mice were then injected with recombinant CTLA-2 alpha (1 µg) into the peritoneal cavity at day 0 and every 2 days after operation. In vitro experiments were performed to assess the inflammatory response by measuring TNF-alpha secretion in peritoneal cavity exudate cells (PECs) or the proliferation of mouse vascular endothelial cells (mVECs). CTLA-2 alpha treatment dramatically suppressed corneal angiogenesis, as well as laser-induced CNV. Moreover, CTLA-2 alpha inhibited the proliferation of mVECs in vitro, while CTLA-2 alpha abolishment was able to rescue proliferation. However, CTLA-2 alpha could not suppress cytokine secretion from inflammatory cells such as PECs. In summary, CTLA-2 alpha was able to suppress angiogenesis by suppressing endothelial cell proliferation. Further studies are needed to investigate its usefulness as a new antiangiogenic treatment for a variety of conditions, including age-related macular degeneration.

Highlights

After sutures were placed on corneas, newly formed vessels sprouted from limbal vessels, and the sprouting vessels reached the suture wound areas around day 7. This model of corneal wounding was used to investigate the effects of recombinant Cytotoxic T lymphocyte antigen-2 (CTLA-2) alpha on hemangiogenesis in the cornea
Hemangiogenesis was quantified by measuring the area covered by newly formed vessels, by measuring the area of
These results showed that a low concentration of CTLA-2 alpha has the ability to suppress cell proliferation, and that diminishing the CTLA-2 alpha function improved and accelerated mouse vascular endothelial cells (mVECs) proliferation (Figure 4b)

Summary

Introduction

Ocular tissues such as the cornea, retina, and especially the macular area, require an avascular condition to maintain good visual acuity. Formed blood vessels are involved in many physiological processes and pathological conditions. Corneal neovascularization (CONV) and choroidal neovascularization (CNV), two forms of ocular angiogenesis, are major causes of blindness worldwide. CNV involves abnormal vessel growth from the choriocapillaris through the Bruch’s membrane, resulting in hemorrhage, scarring, Antioxidants 2021, 10, 456.

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