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Tie2 activation promotes choriocapillary regeneration for alleviating neovascular age-related macular degeneration

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).

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Senescent Cells and Cataract Development

In a recent study, researchers have explored senescence-related proteins and protein interactions in cataracts, a leading cause of visual impairment and blindness in older adults.

Cataracts are characterized by the clouding of the lens in the eye, which leads to impaired vision. Cataracts generally develop slowly and can affect either one or both eyes at the same time. Cataract symptoms typically include faded colors, blurry or double vision, halos around light, trouble with bright lights, and difficulty seeing at night.

By analyzing proteins and their interactions, these researchers aim for a full understanding of this condition, showing that multiple biomarkers associated with aging rise during the formation of cataracts. Typically, p53, a well-known biomarker for the presence of senescent cells, is seen to rise along with transforming growth factor-beta1 (TGF-β1), another biomarker commonly associated with inflammation when encountered in high amounts. During the development of cataracts, the number of senescent cells rises, as this research shows.

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Researchers discover placental stem cells that can regenerate heart after heart attack

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 , in that they can target the site of an injury and travel directly to the injury through the and are able to avoid rejection by the host .”

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 . 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.

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AI Is Rapidly Augmenting Healthcare and Longevity

Conclusion

As Nvidia CEO Jensen Huang has stated, “Software ate the world, but AI is going to eat software.” Extrapolating this statement to a more immediate implication, AI will first eat healthcare, resulting in dramatic acceleration of longevity research and an amplification of the human healthspan.

Next week, I’ll continue to explore this concept of AI systems in healthcare.


Commander (ret) Dr. Luis Alvarez, Director of Organ Manufacturing, United Therapeutics, and Co-Founder of GDF11 Harvard spin-out Elevian and MIT spin-out Theradaptive — ideaXme Show — Ira Pastor

Ending Age-Related Diseases Conference: May Update

May is almost over, so it’s time to check in with the Ending Age-Released Diseases conference and see how things are developing with the event.

If you’re unfamiliar with us, we’re hosting our second annual conference at the Cooper Union in New York City on July 11-12th this year. It will feature some of the leading names in both aging research and biotech business and investment coming together to share their knowledge and insights with the audience.

Aging research is on the cusp of some major breakthroughs in the battle against age-related diseases, and we invite you to join us for an action-packed event filled with exciting talks and discussion panels featuring some of the leaders of aging research and the biotech business.

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