Ghazala Begum1,2, Jenna O'Neill3, Rishika Chaudhary1,2,4, Karen Blachford5, David R J Snead6, Martin Berry1, Robert A H Scott1,2,7, Ann Logan1,2, Richard J Blanch1,2,5,8. 1. Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom. 2. NIHR Surgical Reconstruction and Microbiology Research Centre, University of Birmingham, Birmingham, United Kingdom. 3. Ridgeway Research Ltd., St. Briavels, Gloucestershire, United Kingdom. 4. Ophthalmology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. 5. Academic Unit of Ophthalmology, Birmingham and Midland Eye Centre, Sandwell and West Birmingham Hospitals NHS Trust, Birmingham, United Kingdom. 6. Department of Pathology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, Warwickshire, United Kingdom. 7. SpaMedica, Birmingham, United Kingdom. 8. Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Birmingham, United Kingdom.
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.
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.
Authors: Sana Rasool; Megha Kaushik; Rishika Chaudhary; Karen Blachford; Martin Berry; Robert A H Scott; Ann Logan; Richard J Blanch Journal: Graefes Arch Clin Exp Ophthalmol Date: 2022-01-26 Impact factor: 3.535
Authors: Lisa J Hill; Hannah F Botfield; Ghazala Begum; Omar Qureshi; Vasanthy Vigneswara; Imran Masood; Nicholas M Barnes; Lars Bruce; Ann Logan Journal: NPJ Regen Med Date: 2021-01-07
Authors: Rishika Chaudhary; Robert A H Scott; Graham Wallace; Martin Berry; Ann Logan; Richard J Blanch Journal: Transl Vis Sci Technol Date: 2020-02-21 Impact factor: 3.283
Authors: Shermaine W Y Low; Tanuja Vaidya; Santosh G K Gadde; Thirumalesh B Mochi; Devesh Kumar; Iris S Kassem; Deborah M Costakos; Baseer Ahmad; Swaminathan Sethu; Arkasubhra Ghosh; Shyam S Chaurasia Journal: Life (Basel) Date: 2021-12-17
Authors: Shermaine W Y Low; Thomas B Connor; Iris S Kassem; Deborah M Costakos; Shyam S Chaurasia Journal: Int J Mol Sci Date: 2021-07-07 Impact factor: 5.923