Choriocapillary loss is a major cause of neovascular age-related macular degeneration (NV-AMD). Although vascular endothelial growth factor (VEGF) blockade for NV-AMD has shown beneficial outcomes, unmet medical needs for patients refractory or tachyphylactic to anti-VEGF therapy exist. In addition, the treatment could exacerbate choriocapillary rarefaction, necessitating advanced treatment for fundamental recovery from NV-AMD. In this study, Tie2 activation by angiopoietin-2–binding and Tie2-activating antibody (ABTAA) presents a therapeutic strategy for NV-AMD. Conditional Tie2 deletion impeded choriocapillary maintenance, rendering eyes susceptible to NV-AMD development. Moreover, in a NV-AMD mouse model, ABTAA not only suppressed choroidal neovascularization (CNV) and vascular leakage but also regenerated the choriocapillaris and relieved hypoxia. Conversely, VEGF blockade degenerated the choriocapillaris and exacerbated hypoxia, although it suppressed CNV and vascular leakage. Together, we establish that angiopoietin-Tie2 signaling is critical for choriocapillary maintenance and that ABTAA represents an alternative, combinative therapeutic strategy for NV-AMD by alleviating anti-VEGF adverse effects.

Neovascular age-related macular degeneration (NV-AMD) is a leading cause of irreversible vision loss among elderly persons in developed countries. NV-AMD is characterized by the formation of choroidal neovascularization (CNV), an ingrowth of abnormal blood vessels from the choroid through Bruch’s membrane into the sub-retinal pigment epithelium (RPE) or subretinal space. Throughout this ingrowth, abnormal leakages of fluids and bloods occur into the retina, causing vision distortion and loss of central vision (2, 3). To treat neovascular eye diseases including NV-AMD, anti–vascular endothelial growth factor A (VEGF) therapy has largely been used based on the fact that an excessive production of VEGF from hypoxic cells in the retino-choroidal complex is critical in the pathogenesis and features of neovascular eye diseases (3, 4).

A drug cocktail could be the key.

Researchers at the Icahn School of Medicine at Mount Sinai have demonstrated that stem cells derived from the placenta known as Cdx2 cells can regenerate healthy heart cells after heart attacks in animal models. The findings, published in the May 20 issue of Proceedings of the National Academy of Sciences (PNAS), may represent a novel treatment for regenerating the heart and other organs.

“Cdx2 cells have historically been thought to only generate the placenta in early embryonic development, but never before were shown to have the ability to regenerate other organs, which is why this is so exciting. These findings may also pave the way to regenerative therapy of other organs besides the heart,” said principal investigator Hina Chaudhry, MD, Director of Cardiovascular Regenerative Medicine at the Icahn School of Medicine at Mount Sinai. “They almost seem like a super-charged population of stem cells, in that they can target the site of an injury and travel directly to the injury through the circulatory system and are able to avoid rejection by the host immune system.”

This team of Mount Sinai researchers had previously discovered that a mixed population of mouse placental stem cells can help the hearts of pregnant female mice recover after an injury that could otherwise lead to heart failure. In that study, they showed that the placental stem cells migrated to the mother’s heart and directly to the site of the heart injury. The stem cells then programmed themselves as beating heart cells to help the repair process.

Doctors and patients say they’re compelled to use “off-label” medications as research into anti-aging goes unfunded.

Photomed Laser Surg. 2012 Dec;30(12):681–2. doi: 10.1089/pho.2012.9881. Epub 2012 Nov 9.

No abstract available.