Research Paper Volume 13, Issue 6 pp 8628—8642

Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG

Activation of ATF4 in mice TM induces apoptosis and increase of intraocular pressure. ATF4 adenoviral vectors or GFP adenoviral vectors as control were injected into the anterior chamber of 6~8 weeks old C57BL/6J mice. (A) Visualization of the GFP fluorescence (green) of adenovirus in mice TM after anterior chamber injection for 24 h and increased ATF4 fluorescence (red) could be seen in the ATF4 adenovirus injected eye (Ad-ATF4) compared to the control (Ad-GFP). (B) Intraocular pressure (IOP) of the mice was measured day (left) and night (right) before and after anterior chamber injection. IOP was markedly elevated in the Ad-ATF4 group (n = 8) compared to the control (Ad-GFP) (n = 7) 7 days after the injection, *PC) Immunofluorescent staining of the iridocorneal angle showing increased expression of CHOP (red) in the TM of Ad-ATF4 group after anterior chamber injection for 7 days (n = 3). (D) TUNEL staining of the iridocorneal angle 7 days after anterior chamber injection (n = 3). Arrows mark the TM. Blue, nuclear staining with DAPI. BF, bright field. TM, trabecular meshwork. Scale bar, 50 μm.

Figure 5. Activation of ATF4 in mice TM induces apoptosis and increase of intraocular pressure. ATF4 adenoviral vectors or GFP adenoviral vectors as control were injected into the anterior chamber of 6~8 weeks old C57BL/6J mice. (A) Visualization of the GFP fluorescence (green) of adenovirus in mice TM after anterior chamber injection for 24 h and increased ATF4 fluorescence (red) could be seen in the ATF4 adenovirus injected eye (Ad-ATF4) compared to the control (Ad-GFP). (B) Intraocular pressure (IOP) of the mice was measured day (left) and night (right) before and after anterior chamber injection. IOP was markedly elevated in the Ad-ATF4 group (n = 8) compared to the control (Ad-GFP) (n = 7) 7 days after the injection, *P<0.05 vs. Ad-GFP. (C) Immunofluorescent staining of the iridocorneal angle showing increased expression of CHOP (red) in the TM of Ad-ATF4 group after anterior chamber injection for 7 days (n = 3). (D) TUNEL staining of the iridocorneal angle 7 days after anterior chamber injection (n = 3). Arrows mark the TM. Blue, nuclear staining with DAPI. BF, bright field. TM, trabecular meshwork. Scale bar, 50 μm.