June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
An ER stress sensor PERK is involved in Post-operative Subcojunctival Scarring in a Mouse Model of Glaucoma Filtration Surgery
Author Affiliations & Notes
  • Hidetaka Miyagi
    Ophthalmology and Visual Science, Hiroshima University, Hiroshima City, Japan
  • Soshi Kanemoto
    Biochemistry, Hiroshima University, Hiroshima City, Japan
  • Yoshiaki Kiuchi
    Ophthalmology and Visual Science, Hiroshima University, Hiroshima City, Japan
  • Kazunori Imaizumi
    Biochemistry, Hiroshima University, Hiroshima City, Japan
  • Footnotes
    Commercial Relationships Hidetaka Miyagi, None; Soshi Kanemoto, None; Yoshiaki Kiuchi, None; Kazunori Imaizumi, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 1988. doi:
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      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.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: 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).

Methods: 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.

Results: 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).

Conclusions: 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.

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