Altered Decorin Biology in Proliferative Vitreoretinopathy: A Mechanistic and Cohort Study

Ghazala Begum; Jenna O'Neill; Rishika Chaudhary; Karen Blachford; David R J Snead; Martin Berry; Robert A H Scott; Ann Logan; Richard J Blanch

doi:10.1167/iovs.18-24299

Altered Decorin Biology in Proliferative Vitreoretinopathy: A Mechanistic and Cohort Study

Ghazala Begum, Jenna O'Neill, Rishika Chaudhary, Karen Blachford, David R J Snead, Martin Berry, Robert A H Scott, Ann Logan, Richard J Blanch

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Abstract

Purpose: To determine if vitreous levels of the pro-fibrotic cytokine transforming growth factor beta2 (TGF-β2) and its opposing regulator decorin predict subsequent proliferative vitreoretinopathy (PVR) development in patients with rhegmatogenous retinal detachment (RRD).

Methods: We examined the effect of TGF-β2 and decorin on epithelial-mesenchymal transition (EMT) and collagen expression in vitro using ARPE-19 cells, and we analyzed extracellular matrix marker expression in PVR membrane and internal limiting membrane patient samples. We performed a prospective noninterventional cohort study, recruiting 125 patients undergoing vitrectomy for RRD and macular hole surgery, measured vitreous levels of TGF-β2 and decorin by ELISA, and followed them up for 6 months. Patients who did not develop PVR were compared to those who did, in order to determine whether vitreous TGF-β2 and decorin levels predicted PVR development.

Results: In vitro, TGF-β2 induced EMT and collagen production. Decorin strongly inhibited EMT and collagen production at high levels. PVR membranes expressed high levels of fibrosis-associated proteins, consistent with EMT. Vitreous TGF-β2 levels were unchanged between patients with macular holes and RRD who did or did not subsequently develop PVR. Average decorin levels were higher in the vitreous of RRD patients who subsequently developed PVR compared to those who did not, but at the measured vitreous concentrations (1-2 μg/mL), decorin did not demonstrate an in vitro inhibitory effect on EMT.

Conclusions: In vitro, high concentrations of decorin inhibited EMT and fibrosis. At the levels seen in human vitreous, decorin did not prevent fibrosis or EMT in vitro, and higher initial vitreous decorin levels were associated with the development of postoperative PVR after vitrectomy to treat RRD, but did not reliably predict the outcome.

Original language	English
Pages (from-to)	4929-4936
Number of pages	8
Journal	Investigative Ophthalmology & Visual Science (IOVS)
Volume	59
Issue number	12
DOIs	https://doi.org/10.1167/iovs.18-24299
Publication status	Published - 1 Oct 2018

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@article{0637bb26494e4ab9a05d8c190b949d40,

title = "Altered Decorin Biology in Proliferative Vitreoretinopathy: A Mechanistic and Cohort Study",

abstract = "Purpose: To determine if vitreous levels of the pro-fibrotic cytokine transforming growth factor beta2 (TGF-β2) and its opposing regulator decorin predict subsequent proliferative vitreoretinopathy (PVR) development in patients with rhegmatogenous retinal detachment (RRD).Methods: We examined the effect of TGF-β2 and decorin on epithelial-mesenchymal transition (EMT) and collagen expression in vitro using ARPE-19 cells, and we analyzed extracellular matrix marker expression in PVR membrane and internal limiting membrane patient samples. We performed a prospective noninterventional cohort study, recruiting 125 patients undergoing vitrectomy for RRD and macular hole surgery, measured vitreous levels of TGF-β2 and decorin by ELISA, and followed them up for 6 months. Patients who did not develop PVR were compared to those who did, in order to determine whether vitreous TGF-β2 and decorin levels predicted PVR development.Results: In vitro, TGF-β2 induced EMT and collagen production. Decorin strongly inhibited EMT and collagen production at high levels. PVR membranes expressed high levels of fibrosis-associated proteins, consistent with EMT. Vitreous TGF-β2 levels were unchanged between patients with macular holes and RRD who did or did not subsequently develop PVR. Average decorin levels were higher in the vitreous of RRD patients who subsequently developed PVR compared to those who did not, but at the measured vitreous concentrations (1-2 μg/mL), decorin did not demonstrate an in vitro inhibitory effect on EMT.Conclusions: In vitro, high concentrations of decorin inhibited EMT and fibrosis. At the levels seen in human vitreous, decorin did not prevent fibrosis or EMT in vitro, and higher initial vitreous decorin levels were associated with the development of postoperative PVR after vitrectomy to treat RRD, but did not reliably predict the outcome.",

author = "Ghazala Begum and Jenna O'Neill and Rishika Chaudhary and Karen Blachford and Snead, {David R J} and Martin Berry and Scott, {Robert A H} and Ann Logan and Blanch, {Richard J}",

year = "2018",

month = oct,

day = "1",

doi = "10.1167/iovs.18-24299",

language = "English",

volume = "59",

pages = "4929--4936",

journal = "Investigative Ophthalmology & Visual Science (IOVS)",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology",

number = "12",

}

TY - JOUR

T1 - Altered Decorin Biology in Proliferative Vitreoretinopathy

T2 - A Mechanistic and Cohort Study

AU - Begum, Ghazala

AU - O'Neill, Jenna

AU - Chaudhary, Rishika

AU - Blachford, Karen

AU - Snead, David R J

AU - Berry, Martin

AU - Scott, Robert A H

AU - Logan, Ann

AU - Blanch, Richard J

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Purpose: To determine if vitreous levels of the pro-fibrotic cytokine transforming growth factor beta2 (TGF-β2) and its opposing regulator decorin predict subsequent proliferative vitreoretinopathy (PVR) development in patients with rhegmatogenous retinal detachment (RRD).Methods: We examined the effect of TGF-β2 and decorin on epithelial-mesenchymal transition (EMT) and collagen expression in vitro using ARPE-19 cells, and we analyzed extracellular matrix marker expression in PVR membrane and internal limiting membrane patient samples. We performed a prospective noninterventional cohort study, recruiting 125 patients undergoing vitrectomy for RRD and macular hole surgery, measured vitreous levels of TGF-β2 and decorin by ELISA, and followed them up for 6 months. Patients who did not develop PVR were compared to those who did, in order to determine whether vitreous TGF-β2 and decorin levels predicted PVR development.Results: In vitro, TGF-β2 induced EMT and collagen production. Decorin strongly inhibited EMT and collagen production at high levels. PVR membranes expressed high levels of fibrosis-associated proteins, consistent with EMT. Vitreous TGF-β2 levels were unchanged between patients with macular holes and RRD who did or did not subsequently develop PVR. Average decorin levels were higher in the vitreous of RRD patients who subsequently developed PVR compared to those who did not, but at the measured vitreous concentrations (1-2 μg/mL), decorin did not demonstrate an in vitro inhibitory effect on EMT.Conclusions: In vitro, high concentrations of decorin inhibited EMT and fibrosis. At the levels seen in human vitreous, decorin did not prevent fibrosis or EMT in vitro, and higher initial vitreous decorin levels were associated with the development of postoperative PVR after vitrectomy to treat RRD, but did not reliably predict the outcome.

AB - Purpose: To determine if vitreous levels of the pro-fibrotic cytokine transforming growth factor beta2 (TGF-β2) and its opposing regulator decorin predict subsequent proliferative vitreoretinopathy (PVR) development in patients with rhegmatogenous retinal detachment (RRD).Methods: We examined the effect of TGF-β2 and decorin on epithelial-mesenchymal transition (EMT) and collagen expression in vitro using ARPE-19 cells, and we analyzed extracellular matrix marker expression in PVR membrane and internal limiting membrane patient samples. We performed a prospective noninterventional cohort study, recruiting 125 patients undergoing vitrectomy for RRD and macular hole surgery, measured vitreous levels of TGF-β2 and decorin by ELISA, and followed them up for 6 months. Patients who did not develop PVR were compared to those who did, in order to determine whether vitreous TGF-β2 and decorin levels predicted PVR development.Results: In vitro, TGF-β2 induced EMT and collagen production. Decorin strongly inhibited EMT and collagen production at high levels. PVR membranes expressed high levels of fibrosis-associated proteins, consistent with EMT. Vitreous TGF-β2 levels were unchanged between patients with macular holes and RRD who did or did not subsequently develop PVR. Average decorin levels were higher in the vitreous of RRD patients who subsequently developed PVR compared to those who did not, but at the measured vitreous concentrations (1-2 μg/mL), decorin did not demonstrate an in vitro inhibitory effect on EMT.Conclusions: In vitro, high concentrations of decorin inhibited EMT and fibrosis. At the levels seen in human vitreous, decorin did not prevent fibrosis or EMT in vitro, and higher initial vitreous decorin levels were associated with the development of postoperative PVR after vitrectomy to treat RRD, but did not reliably predict the outcome.

U2 - 10.1167/iovs.18-24299

DO - 10.1167/iovs.18-24299

M3 - Article

C2 - 30347087

SN - 0146-0404

VL - 59

SP - 4929

EP - 4936

JO - Investigative Ophthalmology & Visual Science (IOVS)

JF - Investigative Ophthalmology & Visual Science (IOVS)

IS - 12

ER -

Altered Decorin Biology in Proliferative Vitreoretinopathy: A Mechanistic and Cohort Study

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