AMPK modulation ameliorates dominant disease phenotypes of CTRP5 variant in retinal degeneration
2021
Kiyoharu J. Miyagishima | Ruchi Sharma | Malika Nimmagadda | Katharina Clore-Gronenborn | Zoya Qureshy | Davide Ortolan | Devika Bose | Mitra Farnoodian | Congxiao Zhang | Andrew Fausey | Yuri V. Sergeev | Mones Abu-Asab | Bokkyoo Jun | Khanh V. Do | Marie-Audrey Kautzman Guerin | Jorgelina Calandria | Aman George | Bin Guan | Qin Wan | Rachel C. Sharp | Catherine Cukras | Paul A. Sieving | Robert B. Hufnagel | Nicolas G. Bazan | Kathleen Boesze-Battaglia | Sheldon Miller | Kapil Bharti
Miyagishima et al. investigate the pathological mechanisms underlying mutant CTRP5 function in late-onset retinal degeneration (L-ORD). With human iPSC-derived RPE cells, they demonstrate that in L-ORD iRPE, constitutive activation of AMPK disrupts cellular metabolism/energy homoeostasis, changes apical/basal VEGF secretion, and Metformin treatment corrects these associated phenotypes.
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