| First Author | Ross BX | Year | 2021 |
| Journal | Cells | Volume | 10 |
| Issue | 8 | PubMed ID | 34440779 |
| Mgi Jnum | J:312908 | Mgi Id | MGI:6792751 |
| Doi | 10.3390/cells10082010 | Citation | Ross BX, et al. (2021) Conditional Knock out of High-Mobility Group Box 1 (HMGB1) in Rods Reduces Autophagy Activation after Retinal Detachment. Cells 10(8) |
| abstractText | After retinal detachment (RD), the induction of autophagy protects photoreceptors (PR) from apoptotic cell death. The cytoplasmic high-mobility group box 1 (HMGB1) promotes autophagy. We previously demonstrated that the deletion of HMGB1 from rod PRs results in a more rapid death of these cells after RD. In this work, we tested the hypothesis that the lack of HMGB1 accelerates PR death after RD due to the reduced activation of protective autophagy in the retina after RD. The injection of 1% hyaluronic acid into the subretinal space was used to create acute RD in mice with a rhodopsin-Cre-mediated conditional knockout (cKO) of HMGB1 in rods (HMGB1Deltarod) and littermate controls. RD sharply increased the number of apoptotic cells in the outer nuclear layer (ONL), and this number was further increased in HMGB1Deltarod mouse retinas. The activation of autophagy after RD was reduced in the HMGB1Deltarod mouse retinas compared to controls, as evidenced by diminished levels of autophagy regulatory proteins LC3-II, Beclin1, ATG5/12, and phospho-ATG16L1. The cKO of HMGB1 in rods increased the expression of Fas and the Bax/Bcl-2 ratio in detached retinas, promoting apoptotic cell death. In conclusion, endogenous HMGB1 facilitates autophagy activation in PR cells following RD to promote PR cell survival and reduce programmed apoptotic cell death. |
