Differences in Unfolded Protein Response Pathway Activation in the Lenses of Three Types of Cataracts.

Jing Yang,Jianjun Gu,Yujuan Wang,Sheng Zhou,Minfei Guo,Yizhi Liu,Chen-Wei Pan

doi:10.1371/journal.pone.0130705

Abstract

PurposeTo investigate the activation of three unfolded protein response (UPR) pathways in the lenses of age-related, high myopia-related and congenital cataracts.Methods and MaterialsLens specimens were collected from patients during small incision cataract surgery. Lenses from young cadaver eyes were collected as normal controls. Real-time PCR and Western blotting were performed to detect the expression of GRP78, p-eIF2α, spliced XBP1, ATF6, ATF4 and p-IRE1α in the lenses of normal human subjects and patients with age-related, myopia-related or congenital cataracts.ResultsIn the lenses of the age-related and high myopia-related cataract groups, the protein levels of ATF6, p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78, ATF6 and ATF4 were greatly increased. Additionally, in the congenital cataract group, the protein levels of p-eIF2α and p-IRE1α and the gene expression levels of spliced XBP1, GRP78 and ATF4 were greatly increased. However, the protein and gene expression levels of ATF6 were not up-regulated in the congenital cataract group compared with the normal control group.ConclusionsThe UPR is activated via different pathways in the lenses of age-related, high myopia-related and congenital cataracts. UPR activation via distinct pathways might play important roles in cataractogenesis mechanisms in different types of cataracts.

Highlights

Cataract is a clouding of the lens in the eye that affects vision
The protein and gene expression levels of ATF6 were not up-regulated in the congenital cataract group compared with the normal control group
The unfolded protein response (UPR) is activated via different pathways in the lenses of age-related, high myopiarelated and congenital cataracts

Summary

Introduction

Cataract is a clouding of the lens in the eye that affects vision. The process of cataract initiation remains unclear, even though increasing numbers of related mechanisms have been revealed [1,2,3]. Properly folded proteins are transferred to the Golgi complex for further modification [12]; otherwise, when misfolded proteins accumulate within the ER, the ER chaperone GRP78/ BiP dissociates from the UPR sensors PERK, IRE1 and ATF6 and subsequently binds to improperly folded proteins [13,14] This triggers the activation of these factors and results in the induction of three UPR-related pathways[15]. The IRE1-XBP1 pathway and the ATF6 pathway activation aim to produce a transcriptional response and subsequently increase the capacity of the ER [16]; PERK pathway activation aims to induce temporary translation attenuation [8,17] These three UPR pathways, which can be activated independently, play distinct roles in regulating various physiological processes [17]

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Conclusion