Unfolded protein response activation in cataracts.

Abstract:

PURPOSE:To analyze the expression of 78 kDa glucose-regulated protein (GRP78) and activating transcription factor 6 (ATF6), 2 factors in the unfolded protein response (UPR), in age-related and diabetes-associated cataract. SETTING:Universidad Autónoma de Aguascalientes, Aguascalientes, México. DESIGN:Experimental study. METHODS:The qualitative and quantitative expression of GRP78 and ATF6 were measured in surgical samples from 11 senile cataracts, 9 diabetic-associated cataracts, and 3 normal lenses. Both proteins were detected by immunofluorescence and immunogold-conjugated antibodies. Quantitative morphometry was used to analyze the differences in GRP78 and ATF6 between samples. The Mann-Whitney test was used for statistical analysis. RESULTS:Scanning electron microscopy showed the characteristic organization of fibers in normal lenses with regular alignment and interdigitation between them. On the other hand, lenses from eyes with senile or diabetic cataract showed the same pattern of misalignment and disorganization of the fibers. Both proteins were detected through immunofluorescence in senile and diabetic cataracts, but not in normal lenses. Immunogold-conjugated antibodies and transmission electron microscopy showed that GRP78 and ATF6 grains were 30% higher and 35% higher, respectively, in diabetic cataracts than in senile cataracts (P<.05). CONCLUSIONS:These data show for the first time in humans that GRP78 and ATF6 are present in lens fibers of senile cataracts and diabetic cataracts, establishing that the UPR may be important in the process of cataractogenesis. FINANCIAL DISCLOSURE:No author has a financial or proprietary interest in any material or method mentioned.

authors

Torres-Bernal BE,Torres-Bernal LF,Gutiérrez-Campos RR,Kershenobich Stalnikowitz DD,Barba-Gallardo LF,Chayet AA,Ventura-Juárez J

doi

10.1016/j.jcrs.2014.02.038

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

1697-705

issue

10

eissn

0886-3350

issn

1873-4502

pii

S0886-3350(14)01007-4

journal_volume

40

pub_type

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