Purchase this article with an account.
Hidetaka Miyagi, Soshi Kanemoto, Yoshiaki Kiuchi, Kazunori Imaizumi; An ER stress sensor PERK is involved in Post-operative Subcojunctival Scarring in a Mouse Model of Glaucoma Filtration Surgery. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1988.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Glaucoma is a disease frequently associated with elevated intraocular pressure that can be alleviated by filtration surgery. However, the post-operative subconjunctival scarring response which blocks filtration efficiency is a major hurdle to the achievement of long-term surgical success. In this study, we analyzed relationship between post-operative scarring and unfolded protein response (UPR).
To investigate the gene which is expressing in the tissue of post-operative scar, we created a murine model of glaucoma filtration surgery. We extracted mRNA from the subconjunctival tissue after filtration surgery, and performed RT-PCR. Additionally we stimulated primary mouse embryonic fibroblasts (MEFs) with TGF-β that is known to induce a fibrotic response, and then analyzed the expression of fibrotic genes and UPR-related genes.
We found the up-regulation of UPR-related genes such as BiP and ATF4 as well as fibrotic genes in the post-operative subconjunctival tissue (p<0.05). In knockout MEFs of PERK which is one of the ER stress sensors, the expression of two fibrotic genes, type I collagen (p=0.02) and alpha-smooth muscle actin (α-SMA) (p=0.002), was suppressed when the cells were stimulated with TGF-β. In primary murine subconjunctival fibroblast cells, knockdown of PERK also caused reduction of type I collagen (p=0.03). Furthermore, these genes were decreased in the post-operative subconjunctival tissue glaucoma filtration surgery model in PERK-null mice compared with wild-type mice (p<0.05).
We have demonstrated that the up-regulation of type I collagen and α-SMA of the post-operative subconjunctival scar in fibroblasts could be regulated by PERK pathway. Chemical compounds that regulate the PERK pathway may have potential as therapeutic agents to suppress the post-operative subconjunctival scarring and to achieve long-term surgical success for glaucoma.
This PDF is available to Subscribers Only