Epo inhibits the fibrosis and migration of Müller glial cells induced by TGF-ß and high glucose.

BACKGROUND: In proliferative diabetic retinopathy (PDR), Müller glial cells (MGCs) acquire migratory ability and exhibit a fibroblast-like phenotype. These activated MGCs contribute to the formation of epiretinal membrane, which will stretch the retina, and cause retinal detachment and vitreous hemorrhage. Erythropoietin (Epo) is now found effective in ameliorating renal fibrosis by inhibiting epithelial-to-mesenchymal transition of tubular epithelial cells. This study is undertaken to determine whether Epo has an effect in inhibiting MGCs activation to attenuate epiretinal membrane formation in PDR. METHOD: MIO-M1 cell line was used in this study. As a pilot test to determine the most efficient treatment time and concentration of Epo, levels of connective tissue growth factor (CTGF) and transforming growth factor-ß (TGF-ß) were measured by real-time PCR, after treatment with Epo on MGCs cultured in high glucose. MGCs were cultured in high glucose and normal glucose for 2 days, with or without TGF-ß as a pro-fibrogenic cytokine. Epo was introduced at the same time. Immunofluorescence targeting α-smooth muscle actin (α-SMA), fibronectin, and glial fibrillary acidic protein (GFAP) was performed to explore the cell phenotype. Matrix metalloproteinase 9 (MMP9) mRNA level was detected by real-time PCR. Protein levels of CTGF and cytoskeletal proteins like α-SMA and fibronectin were measured by enzyme-linked immunosorbent assay (ELISA) and Western blot respectively. Wound-healing assay was applied to evaluate the migratory ability of MGCs, and actin-tracker green was used to draw the structure of F-actin in MGCs. RESULTS: After being seeded into high-glucose medium containing TGF-ß, MGCs expressed a larger amount of MMP9 mRNA as well as α-SMA, fibronectin at protein level. They secreted more CTGF, and their F-actin reorganized in a parallel manner and showed a stronger ability to migrate. In addition, these changes, including mRNA and protein expression, F-actin assembling, and cell migration, could be attenuated significantly by Epo treatment. CONCLUSION: High glucose together with TGF-ß promote MGCs to exhibit a fibroblast-like phenotype and develop a greater migratory ability. These changes can be inhibited by Epo, which therefore may contribute to the controlling of epiretinal membrane formation.

Incidence of Epiretinal Membrane Formation After Pars Plana Vitrectomy for Giant Retinal Tear-Associated Retinal Detachment.

Objective: To report the incidence of postoperative epiretinal membrane (ERM) formation after primary pars plana vitrectomy (PPV) for giant retinal tear associated retinal detachment (GRT-RD) repair as well as its clinical characteristics and visual outcomes at a level one trauma and tertiary referral academic center. Patients and Methods: Patients with primary RD repair for GRT-RD at West Virginia University from September 2010 to July 2021 were identified using the ICD-10 codes (H33.031, H33.032, H33.033 and H33.039). Imaging studies including optical coherence tomography (OCT) were manually reviewed pre- and post-operatively for ERM formation after PPV for GRT-RD repair in patients who underwent PPV or combined PPV and scleral buckle (SB). Univariate analysis was performed to analyze clinical factors for ERM formation. Results: The study included 17 eyes of 16 patients who underwent PPV for GRT-RD. Postoperative ERM was observed in 70.6% (13 of 17 eyes) of the patients. Anatomic success was achieved in all patients. The mean (range) preoperative and final best corrected visual acuity (BCVA) in logMAR units by macula status was 0.19 (0-0.5) and 0.28 (0-0.5) for macula-on and 1.7 (0.5-2.3) and 0.7 (0.2-1.9) for macular-off GRT-RDs. Clinical variables including use of medium-term tamponade with perfluorocarbon liquid (PFCL), cryopexy, endodiathermy, number of tears or total clock hours of tears did not correlate with an increased risk of ERM formation. Conclusion: Post-vitrectomized eyes for GRT-RD repair have a significantly higher incidence of ERM formation, nearing 70% in our study. Surgeons may consider prophylactic ILM peel at the time of removal of tamponade agents or weigh in ILM peel at the time of primary repair, a more challenging surgical technique in our opinion.

En Face Image-Based Analysis of Epiretinal Membrane Formation after Surgery for Idiopathic Epiretinal Membrane.

PURPOSE: To analyze en face epiretinal membrane (ERM) images constructed using swept-source (SS) OCT and to determine the incidence of ERM formation after ERM surgery and its effects on visual function. DESIGN: Retrospective, consecutive observational study. PARTICIPANTS: Consecutive series of 73 eyes (71 patients) with idiopathic ERM that underwent vitrectomy with both ERM and internal limiting membrane (ILM) peeling. METHODS: We retrospectively reviewed the data of the 73 eyes included in the study. During surgery, the ERM was removed as extensively as possible, and the ILM was removed such that the area of ILM peeling was at least larger than the parafoveal area. All patients underwent comprehensive ophthalmologic examinations, including assessments of best-corrected visual acuity and metamorphopsia, before and at 2 weeks and 6 months after the surgery. En face images constructed using SS OCT were used to investigate ERM formation. MAIN OUTCOME MEASURES: The incidence of ERM formation at 6 months after the surgery, effects of ERM formation on visual function, and the relationship between ERM formation and the extent of ERM and ILM peeling. RESULTS: At 6 months after ERM and ILM peeling, 8 eyes (11.0%) showed ERM formation (formation group). Twenty eyes (27.4%) exhibited remnant ERM without ERM formation (remnant group), whereas 45 eyes (61.6%) showed no ERM (no ERM group). In both the remnant and no ERM groups, best-corrected visual acuity and metamorphopsia showed significant improvements after ERM surgery (both P < 0.01); these improvements were not seen in the formation group (P = 0.067 and P = 0.053, respectively). However, no significant differences were found in preoperative and postoperative best-corrected visual acuities and metamorphopsia among the 3 groups. In the formation group, ERM formation occurred only in the area with residual ILM. Most patients who underwent ILM peeling in which the area of the peeling covered the ERM belonged to the no ERM group (97.7%; P < 0.01). CONCLUSIONS: Epiretinal membrane formation does not affect visual function significantly when the area of ILM peeling is larger than the parafoveal area. When the ILM peeling area covers the ERM area, postoperative ERM formation can be prevented.

[Proliferative vitreoretinopathy (PVR) minimal: same, same but different. Characteristics and surgical treatment of PVR-associated macular pucker]. / Proliferative Vitreoretinopathie (PVR) minimal: "Same same, but different". Besonderheiten und chirurgische Therapie des PVR-assoziierten Makula-Puckers.

BACKGROUND: Epiretinal membrane formation resulting in a macular pucker is among the typical complications associated with proliferative vitreoretinopathy (PVR) in retinal detachment and has a major impact on the functional outcome after surgical treatment. METHODS: A literature search was carried out in PubMed. RESULTS: Approaches to the surgical treatment of PVR-associated macular pucker include complete membrane removal within the vascular arcades aimed at relieving retinal traction at the posterior pole and peeling of the internal limiting membrane (ILM). As a further option it has been suggested that primary ILM peeling in rhegmatogenous retinal detachment repair may reduce or even prevent postoperative epiretinal membrane formation. In addition, correct timing of surgery is a factor that may contribute to successful treatment. DISCUSSION: Due to the particularly strong adhesion and the frequent occurrence of concurrent retinal detachment, the surgical approach to PVR-associated macular pucker is particularly challenging. As with idiopathic epiretinal membranes, surgical removal has the potential to improve functional outcomes; however, visual improvement depends largely on whether the macula was involved in the original retinal detachment.