Proliferative Vitreoretinopathy Research Articles

The Wisconsin silicone oil study (report #1): anatomical and functional outcomes of repair of retinal detachment with proliferative vitreoretinopathy.

Silicone oil (SO) is a long-term tamponade for repair of complex retinal pathology but has limitations including late redetachment. This study describes our experience with SO tamponade for repair of retinal detachment with proliferative vitreoretinopathy (PVR), with attention to anatomic and functional outcomes. Retrospective consecutive case series of eyes with retinal detachment (RD) complicated by proliferative vitreoretinopathy (PVR) receiving SO tamponade at the University of Wisconsin between 2013 and 2019. Group 1 defined as primary SO placement; Group 2 had SO placed after failing prior retinal detachment repair. Inclusion criteria of SO placement for repair of RD with PVR was met for 117 eyes. The final reattachment rate was 84% for all eyes, with no difference between Groups 1 and 2. Vision improvement was 2.1 lines for Group 1 (p = 0.06 from baseline) and 4.6 lines for Group 2 (p < 0.0001). The mean number of silicone oil placements was 1.4. Less improvement in vision was noted with repeat SO placement, though overall functional vision of 5/200 or better was achieved in 63.2% of patients. SO tamponade allows long-term anatomical stabilisation and substantial vision recovery in eyes with retinal detachment complicated by PVR. Rates of anatomic and functional success have improved significantly when compared to prior studies using oil tamponade for repair of PVR.

Open-Globe Injury With Globe Penetration Leading to Complex Retinal Detachment After Intraoral Anesthetic Injection

Purpose: To report a case of a suspected open-globe injury and globe penetration complicated by a rhegmatogenous retinal detachment (RRD) after administration of intraoral anesthetic injections during an endodontic procedure. Methods: A retrospective chart review was performed. Results: A 34-year-old woman presented with acute onset of flashes, floaters, and a curtain-like shadow across her field of vision. Four days previously, she had multiple left-sided anesthetic injections during an endodontic procedure. The visual acuity (VA) in the left eye was 20/25. Ophthalmoscopy showed a suspected globe-penetration site inferiorly, associated multilayered hemorrhages, and adjacent subretinal fluid. Laser demarcation of the inferior RRD was performed at sequential clinical visits. Through 8 months, the multilayered hemorrhages improved while proliferative vitreoretinopathy–associated tissue formation over the posterior pole caused macular distortion and mild visual deterioration. The VA in the left eye was 20/40 at the last follow-up. Conclusions: Iatrogenic globe penetration during intraoral anesthesia delivery associated with an endodontic procedure may result in globe injury.

ADDITIONAL PNEUMATIC RETINOPEXY IN PATIENTS WITH PERSISTENT RETINAL DETACHMENT AFTER SCLERAL BUCKLING.

To investigate the efficacy, safety, and indications for additional pneumatic retinopexy (PR) in patients with persistent retinal detachment after scleral buckling. This retrospective study included patients who underwent additional PR after scleral buckling for primary rhegmatogenous retinal detachment (n = 78). We defined "inadequate buckle" as retinal detachment persistence because of low buckle height despite accurate buckle placement and "buckle misplacement" as an uncovered tear because of incorrect buckle placement. The anatomical success rate after additional PR was 52.6%. Development of proliferative vitreoretinopathy Grade B (hazard ratio, 5.73; P < 0.001) and inferior retinal tears (hazard ratio, 2.12; P = 0.040) were significant risk factors for anatomical failure. The most common cause of anatomical failure was proliferative vitreoretinopathy (19 of 37; 51.4%), and epiretinal membrane formation was a common complication after additional PR (22 of 78; 28.2%). The anatomical success rate with additional PR was significantly higher in the inadequate buckle group than in the misplacement group (8 of 9 [88.9%] vs. 1228 [42.9%]; P = 0.023). Development of proliferative vitreoretinopathy Grade B and inferior retinal tears were significantly associated with anatomical failure after additional PR. Additional PR may benefit patients with superior retinal tears or low buckle height and those without proliferative vitreoretinopathy.

Serial Intravitreal Methotrexate Injections to Combat Recurrent Proliferative Vitreoretinopathy in a Pediatric Patient

Purpose: To describe the use of serial intravitreal methotrexate to combat proliferative vitreoretinopathy (PVR) in a pediatric patient with recurrent retinal detachment (RD). Methods: A retrospective case analysis was performed. Results: A 6-year-old patient with bilateral panuveitis presented with recurrent RD in the right eye. After treatment with 2 RD surgeries performed elsewhere, the patient developed PVR that necessitated 5 additional surgeries for recurrent detachment. The patient subsequently received a total of 8 injections of methotrexate 400 µg/0.1 mL (0.1 mL) in the operating room at 1- to 2-week intervals over a 3-month period. Through 13 months of follow-up after the first methotrexate injection, there was no evidence of recurrent RD, PVR, or epiretinal membrane formation. Conclusions: Frequent serial intravitreal methotrexate injections apparently played a role in preventing recurrent PVR formation in this pediatric patient with a history of intraocular inflammation and recurrent RD.

The Effect of Steroid Intervention before Vitrectomy for Rhegmatogenous Retinal Detachment Associated with Choroidal Detachment: A Meta-Analysis and Systematic Review

Purpose This meta-analysis discusses the effectiveness of steroid intervention before vitrectomy in patients with rhegmatogenous retinal detachment associated with choroidal detachment. Methods We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for randomized controlled trials and observational studies published until August 2023. We included studies involving: patients with rhegmatogenous retinal detachment associated with choroidal detachment with proliferative vitreoretinopathy; an experimental group that was not administered steroids and a control group that was administered steroids; and assessment of visual acuity, retinal reattachment rate, and complications. The heterogeneity, publication bias, and sensitivity analysis were performed to ensure the statistical power and reliability of the analysis. Results Two randomized controlled trials and four case-control studies involving 490 eyes were included in the meta-analysis. There were no significant differences in the primary and final retinal reattachment rates after surgery between the steroid and non-steroid groups (primary retinal reattachment rate: odds ratio = 1.01, 95% confidence interval = 0.63–1.63, p = .41; final retinal reattachment rate: odds ratio = 0.82, 95% confidence interval = 0.43–1.59, p = .33). There was no statistically significant difference in postoperative visual acuity improvement between the two groups (odds ratio = 1.19, confidence interval = 0.63–2.25, p = .69). In addition, subgroup analyses of different types of steroids showed that systemic and local administration of steroids had similar results for retinal reattachment rate and visual acuity improvement. Conclusion Patients with rhegmatogenous retinal detachment associated with choroidal detachment who did not receive preoperative steroids achieved the same effect as patients with rhegmatogenous retinal detachment associated with choroidal detachment who did receive preoperative steroids in terms of retinal reattachment rate and visual acuity. It is recommended that patients with rhegmatogenous retinal detachment associated with choroidal detachment undergo surgery as promptly as possible.

Enantiomeric Agonists of the Type 2 Cannabinoid Receptor Reduce Retinal Damage during Proliferative Vitreoretinopathy and Inhibit Hyperactive Microglia In Vitro

Enantiomeric Agonists of the Type 2 Cannabinoid Receptor Reduce Retinal Damage during Proliferative Vitreoretinopathy and Inhibit Hyperactive Microglia <i>In Vitro</i>

Tricetin suppresses the cell migration and BMP-6 expression through p38 signaling pathways in human retinal pigment epithelium cells.

Proliferative vitreoretinopathy (PVR) is a visual-threatening disease, which cause from the migration of retinal pigment epithelium (RPE). Tricetin, a family of flavonoids, can inhibit the metastasis of several cancers. Herein, we aim to evaluate the possible effect of tricetin on inhibiting ARPE-19 cells migration. The Boyden chamber assay, wound healing assay, RNA sequencing, and Western blot analysis were applied in our experiment. The results revealed that tricetin inhibited the cell migration abilities of ARPE-19 cells. Moreover, using RNA sequencing technology, we revealed that tricetin repressed bone morphogenetic protein-6 (BMP-6) gene expressions in ARPE-19 cells. Overexpression of BMP-6 resulted in significant restoration of cell migration capabilities of tricetin-treated ARPE-19 cells. Furthermore, tricetin suppressed the phosphorylation of the p38 signaling pathway. Moreover, blocking the p38 pathway also inhibits BMP-6 expression and migration in the ARPE-19 cells. In conclusion, this study revealed that tricetin inhibits the ARPE-19 cell migration mainly via the suppression of BMP-6 expression and p38 signaling pathway.

Management of macula-on giant retinal tear detachments– outcome of pars-plana-vitrectomy with silicone oil versus gas tamponade

BackgroundTo compare the outcome of eyes with a macula-on giant retinal tear (GRT) detachment treated with pars-plana-vitrectomy (PPV) depending on the used endotamponade.MethodsAll consecutive cases with a macula-on GRT-associated rhegmatogenous retinal detachment (RRD) managed with PPV between 2007 and 2022 were retrospectively assessed depending on the selected endotamponade. By reviewing medical charts and surgical protocols the pre- and intraoperative parameters were analysed in detail. The number of vitreoretinal (VR) procedures needed for reattachment, the redetachment rate and the functional outcome were evaluated. Eyes treated with primary silicone oil (SO) tamponade were compared to eyes with primary gas tamponade. Cases with pre-existing conditions affecting outcome e.g. macula-off situation, history of trauma, status after complicated cataract surgery, former VR surgery or proliferative vitreoretinopathy grade C or higher were excluded.ResultsOverall, 51 eyes of 45 patients with a macula-on GRT detachment were treated with PPV and SO (n = 32; 63%) or gas (n = 19; 37%) endotamponade in the observed period. Eyes with primary SO tamponade underwent on average 2.3 (SD 0.8) VR procedures and had a redetachment rate of 13% (n = 4). Eyes with gas tamponade showed a higher redetachment rate of 32% (n = 6) with a mean number of 1.6 (SD 1.0) PPV procedures. Postoperative best-corrected visual acuity (BCVA) was significantly better in eyes with primary gas tamponade (mean logMAR BCVA 0.32; SD 0.30) compared to eyes with SO (mean logMAR BCVA 0.60; SD 0.42; p = 0.008).ConclusionsSurgical management of GRT-associated RRDs is complex. In clinical routine often SO is used as endotamponade. Because of known disadvantages (second procedure necessary for SO removal, unexplained SO-related visual loss, secondary glaucoma, SO emulsification) some VR surgeons prefer a gas tamponade. In our cohort, eyes with a gas compared to SO tamponade showed higher redetachment rates. However, the final postoperative BCVA was significantly better in eyes with gas compared to SO tamponade.Trial registrationThe trial protocol was approved by the local ethics committee on 25th of November 2022 (Ethikkommission der Universität Regensburg, Votum 22-3166-104).

Bone morphogenetic protein-6 suppresses TGF-β2-induced epithelial-mesenchymal transition in retinal pigment epithelium.

To evaluate the effect of bone morphogenetic protein-6 (BMP-6) on transforming growth factor (TGF)-β2-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelium (RPE). Adult retinal pigment epithelial cell line (ARPE-19) were randomly divided into control, TGF-β2 (5 µg/L), and BMP-6 small interfering RNA (siRNA) group. The cell morphology was observed by microscopy, and the cell migration ability were detected by Transwell chamber. The EMT-related indexes and BMP-6 protein levels were detected by Western blotting. Furthermore, a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group, TGF-β2+empty plasmid group, BMP-6 overexpression group, and TGF-β2+BMP-6 overexpression group. The EMT-related indexes and extracellular regulated protein kinases (ERK) protein levels were detected. Compared with the control group, the migration of RPE cells in the TGF-β2 group was significantly enhanced. TGF-β2 increased the protein expression levels of α-smooth muscle actin (α-SMA), fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6 (P<0.05) in RPE. Similarly, the migration of RPE cells in the BMP-6 siRNA group was also significantly enhanced. BMP-6 siRNA increased the protein expression levels of α-SMA, fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin (P<0.05). Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β2 and prevented TGF-β2 from affecting EMT-related biomarkers (P<0.05). BMP-6 prevents the EMT in RPE cells induced by TGF-β2, which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

Outcomes after giant peripheral retinotomy and anterior flap retinectomy for rhegmatogenous retinal detachments with advanced proliferative vitreoretinopathy using small gauge vitrectomy.

To analyze the visual and anatomical outcomes for eyes with rhegmatogenous retinal detachment (RRD) and advanced proliferative vitreoretinopathy (PVR) undergoing giant peripheral retinotomy (GPR) using 25-gauge pars plana vitrectomy (PPV). In this retrospective multi-center study, patients with RRD with either anteroposterior or circumferential retinal shortening and advanced PVR requiring more than 90-degree GPR with/without relaxing retinotomy were included. Subjects of either gender, any age group, and with complete surgical notes were included. Outcome measures of the study included anatomical success (i.e. complete retinal re-attachment) at 6 months using survival analysis, visual outcomes, and post-operative complications. Forty-one eyes of 41 patients (33 males) with a mean age of 44.9 ± 21.4 years were included. At 6 months follow-up, anatomical success was seen in 29 eyes (70.7%) with a cumulative re-attachment rate of 66% (95% confidence interval = 48 = 79%). All re-detachments occurred at ≤6 months with a peak at 4-6 months (n = 9). Twenty-three eyes (56%) achieved ambulatory vision (5/200) or better. Direct perfluorocarbon liquid-silicone oil exchange was performed in 20 eyes. Intra-operative complications included persistent retinal folds (2 eyes), subretinal air (1 eye), and subretinal bleed (1 eye). Eleven eyes (26.8%) developed secondary glaucoma (2 eyes required a drainage device), and hypotony of ≤6 mmHg was noted in 3 eyes (7.3%). Corneal decompensation was noted in 8 eyes (19.5%), and 3 eyes (7.3%) underwent re-surgery for re-RRD. After GPR using small gauge PPV, two-thirds achieve anatomical success, and over half have ambulatory vision, but overall post-operative complications can occur in more than half of the eyes.

Retrospective case series of high-density silicone oil (Oxane HD) in severe proliferative vitreorretinal retinal detachment patients

BackgroundDescribe complications and clinical outcomes of heavy silicone oil (HSO) Oxane HD® use as an alternative to overcome the challenges of performing vitrectomy to treat tractional and rhegmatogenous retinal detachments with proliferative vitreoretinopathy (PVR).MethodsA retrospective, observational study was performed on patients from one center from August 2014 to Aug 2023. It was included patients who underwent surgery using HSO Oxane HD® to treat rhegmatogenous retinal detachment with PVR or mixed tractional and rhegmatogenous diabetic retinal detachment. Severely ill patients who could not attend to follow up were excluded. The primary outcome was successful retinal attachment at first postoperative month. A descriptive analysis was performed.ResultsAmong the 31 patients, 29 (93.5%) underwent surgeries due to rhegmatogenous retinal detachment and two (6.5%) for diabetic retinal detachment. The primary anatomic success was achieved in 27 (87.1%) patients. At the final visit, 17 (56.6%) had vision better than 20/400 (range, 20/30 to light perception). The vision was stable or improved in 22 (76.8%) patients at the end of follow-up. Nineteen (61.3%) patients required hypotensive eye drops after HSO use and twelve (38.7%) still required hypotensive eye drops at the final follow-up; three (9.7%) patients required additional glaucoma surgeries.ConclusionsHSO is safe and useful for complex retinal detachments cases specially with inferior tears and PVR. Ocular hypertension is frequent and usually clinically controlled with hypotensive eyedrops. Close postoperatively follow-up is advised due to the ocular complications, particularly elevated intraocular pressure and emulsification.

A simulacrum of proliferative vitreoretinopathy (PVR): development and proteomics-based validation of an in vitro model

A simulacrum of proliferative vitreoretinopathy (PVR): development and proteomics-based validation of an in vitro model

Traumatic terson syndrome with a peculiar mass lesion and tractional retinal detachment: a case report

BackgroundTo report a case with bilateral Terson syndrome presented with a unique mushroom-like mass lesion on the optic disc along with proliferative vitreoretinopathy and tractional retinal detachment.Case presentationA 33-year-old man was injured during a traffic accident and had diffuse brain swelling and intraocular hemorrhage. Poor vision in both eyes was noted after the patient regained consciousness. B-scan ultrasonography showed extensive vitreous opacity with a posterior vitreous detachment and without obvious retinal detachment. Vitrectomy was performed in both eyes five months after the accident. After clearing up the vitreous opacity, a peculiar pigmented mushroom-like mass lesion was noted in the posterior pole and had severe adhesion to the underneath optic disc. Extensive multilayered peripapillary epiretinal membrane was found covering the posterior pole and led to tractional retinal detachment around the macula. The mass was presumed to be an organized vitreous hemorrhage originated from the optic disc. The extensive and adherent epiretinal membrane together with the mass lesion were removed as much as possible and silicon oil was injected for tamponade. However, in the right eye, the retina redetached under silicon oil, whereas in the left eye, his vision improved to 20/100.ConclusionsTerson syndrome usually has a favorable prognosis but may be complicated by proliferative vitreoretinopathy and tractional retinal detachment. Careful monitoring is warranted and early vitrectomy should be considered in cases suspecting additional pathologies.

Hyalocytes-guardians of the vitreoretinal interface.

Originally discovered in the nineteenth century, hyalocytes are the resident macrophage cell population in the vitreous body. Despite this, a comprehensive understanding of their precise function and immunological significance has only recently emerged. In this article, we summarize recent in-depth investigations deciphering the critical role of hyalocytes in various aspects of vitreous physiology, such as the molecular biology and functions of hyalocytes during development, adult homeostasis, and disease. Hyalocytes are involved in fetal vitreous development, hyaloid vasculature regression, surveillance and metabolism of the vitreoretinal interface, synthesis and breakdown of vitreous components, and maintenance of vitreous transparency. While sharing certain resemblances with other myeloid cell populations such as retinal microglia, hyalocytes possess a distinct molecular signature and exhibit a gene expression profile tailored to the specific needs of their host tissue. In addition to inflammatory eye diseases such as uveitis, hyalocytes play important roles in conditions characterized by anomalous posterior vitreous detachment (PVD) and vitreoschisis. These can be hypercellular tractional vitreo-retinopathies, such as macular pucker, proliferative vitreo-retinopathy (PVR), and proliferative diabetic vitreo-retinopathy (PDVR), as well as paucicellular disorders such as vitreo-macular traction syndrome and macular holes. Notably, hyalocytes assume a significant role in the early pathophysiology of these disorders by promoting cell migration and proliferation, as well as subsequent membrane contraction, and vitreoretinal traction. Thus, early intervention targeting hyalocytes could potentially mitigate disease progression and prevent the development of proliferative vitreoretinal disorders altogether, by eliminating the involvement of vitreous and hyalocytes.

A Comparative Analysis of Traumatic Retinal Detachment After Open and Closed Globe Injuries in Children.

Pediatric traumatic retinal detachment (RD) resulting from open globe (OGI) or closed globe injuries (CGI) presents unique challenges due to complexity often resulting in lifelong sequelae. This study compares pediatric traumatic RD outcomes and prognostic factors following OGI and CGI. A retrospective analysis reviewed 47 cases of pediatric traumatic RD cases (age <18 years) undergoing retinal detachment surgery between 2002 and 2021. Among them, 25 cases were caused by CGI and 22 cases by OGI. Demographics, retinal detachment characteristics, surgical procedures, anatomical and functional results were assessed. Predictive factors for visual outcomes were investigated. In the CGI group, mean (± standard deviation) age was 11 ± 4 years, and 10 ± 5 years in the OGI group. CGI traumatic RD had significantly better preoperative (CGI: logMAR 1.39 ± 0.19 (mean ± standard error); OGI: logMAR 2.12 ± 0.20) and follow-up (CGI: logMAR 0.94 ± 0.19; OGI: logMAR 1.85 ± 0.20) best corrected visual acuity (BCVA) (p<0.05). Initial BCVA improvement was observed in CGI only. In multivariable analysis, prognostic factors for favorable BCVA outcomes included higher preoperative BCVA, older age and absence of proliferative vitreoretinopathy (p<0.05). Visual prognosis for pediatric traumatic RD remains limited, favoring CGI cases compared to OGI. Baseline BCVA emerged as major determinant of final visual acuity. Tailored management approaches can optimize treatment results.

Visual and Surgical Outcomes in Late Presentation of Retinal Detachment

Purpose:  To evaluate the frequency of treatment success in terms of visual and surgical outcomes in patients with late presentation of retinal detachment. Study Design:  Quasi experimental. Place and Duration of Study:  Sindh institute of Ophthalmology and visual Sciences from June 2022 to January 2023. Methods:  A total of 50 eyes of 50 patients with delayed presentation of retinal detachment who underwent Pars Plana Vitrectomy (PPV) were included and followed up for 6 months. Preand post-surgery Best Corrected Visual Acuity (BCVA) and anatomical attachment of retina were comprehensively analyzed. Factors affecting an atomical success were also studied. Results:  Mean age of patients was 47±18 years. Twenty seven patients were (54%) were more than 45 years of age and 32(64%) were males. Thirty eight (76%) patients achieved successful anatomical attachment of retina at 6th month follow-up. Post-operative BCVA also showed improvement in vision.Risk factors identified for poor anatomical and visual outcome following PPV for retinal detachment are; PVR advance stage, longer duration of visual symptoms and poor-presenting BCVA. Age, sex, laterality, Pre-operative BCVA, lens status, diagnosis, and type of surgery showed insignificant associations (P &gt;0.05). Conclusion:  Anatomical failure and poor functional outcomes appear to be mostly caused by PVR. PVR, longer duration of visual symptoms and poor-presenting VA are risk factors for poor anatomical and visual outcome following PPV surgery for RD. Late presentations to clinics can decrease with mass awareness. The frequency of  proliferative vitreoretinopathy would decline, and visual results would be improved.

Anti-inflammatory potential of simvastatin and amfenac in ARPE-19 cells; insights in preventing re-detachment and proliferative vitreoretinopathy after rhegmatogenous retinal detachment surgery

PurposeRhegmatogenous retinal detachment is a severe vision-threatening complication that can result into proliferative vitreoretinopathy (PVR) and re-detachment of the retina if recovery from surgery fails. Inflammation and changes in retinal pigment epithelial (RPE) cells are important contributors to the disease. Here, we studied the effects of simvastatin and amfenac on ARPE-19 cells under inflammatory conditions.MethodsARPE-19 cells were pre-treated with simvastatin and/or amfenac for 24 h after which interleukin (IL)-1α or IL-1β was added for another 24 h. After treatments, lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) processing, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity, prostaglandin E2 (PGE2) level, and extracellular levels of IL-6, IL-8, monocytic chemoattractant protein (MCP-1), vascular endothelial growth factor (VEGF), and pigment epithelium-derived factor, as well as the production of reactive oxygen species (ROS) were determined.ResultsPre-treatment of human ARPE-19 cells with simvastatin reduced the production of IL-6, IL-8, and MCP-1 cytokines, PGE2 levels, as well as NF-κB activity upon inflammation, whereas amfenac reduced IL-8 and MCP-1 release but increased ROS production. Together, simvastatin and amfenac reduced the release of IL-6, IL-8, and MCP-1 cytokines as well as NF-κB activity but increased the VEGF release upon inflammation in ARPE-19 cells.ConclusionOur present study supports the anti-inflammatory capacity of simvastatin as pre-treatment against inflammation in human RPE cells, and the addition of amfenac complements the effect. The early modulation of local conditions in the retina can prevent inflammation induced PVR formation and subsequent retinal re-detachment.

Internal limiting membrane peeling in vitreoretinal surgery for rhegmatogenous retinal detachment: clinical results, surgical options, and future prospects

Rhegmatogenous retinal detachment (RRD) is one of the leading causes of primary vision disability, while the majority of RRD patients with RRD are people of active working age. Over the past 50 years, retinal detachment surgery has been progressing rapidly, the rate of success increasing up to 90% or higher. However, the reduction of reoperation risks of reoperations, improvement of functional outcomes and increase of postoperative visual acuity remain topical issues. The main reason for repeated surgical interventions is the proliferative vitreoretinopathy progression, which can lead to epiretinal fibrosis, macular oedema, or retinal detachment recurrence. The review is focused on current literature studies that report the results of internal limiting membrane peeling in cases of RRD surgeries and other optional techniques aimed at reducing the risk of the above mentioned postoperative complications.

Comparative Study of Combined Pars Plana Vitrectomy-Scleral Buckle versus Pars Plana Vitrectomy in Cases of Inferior Retinal Break with Proliferative Vitreoretinopathy

Comparative Study of Combined Pars Plana Vitrectomy-Scleral Buckle versus Pars Plana Vitrectomy in Cases of Inferior Retinal Break with Proliferative Vitreoretinopathy

ABCA4 mediated traumatic proliferative vitreoretinopathy associated with PI3K/Akt signaling pathway

BackgroundProliferative vitreoretinopathy (PVR) is the main cause of retinal detachment. However, the underlying mechanism of PVR is complex and has not yet been fully elucidated. The PI3K/Akt/mTOR signaling pathway is involved in angiogenesis and plays an important role in cell proliferation and tumor formation. Therefore, our study was designed to investigate the potential biological mechanisms of alleviating ARPE-19 cell and traumatic PVR model involving PI3K/Akt signaling pathway by targeting ABCA4. Materials and methodsARPE-19 cell model was induced by ABCA4 overexpression vector and si-ABCA4, then the ABCA4 overexpression vector and si-ABCA4 were constructed, the plasmids were expanded for cell transfection and verification. In addition, OE-ABCA4, shRNA NC and si-ABCA4 were transfected into ARPE-19 cells. Cell viability was detected by CCK-8 assay, cell cycle was determined by flow cytometry. The expression level and location of ABCA4 were detected by immunofluorescence. Finally, rabbit traumatic PVR model was induced by surgery, the adenovirus was injected into the vitreous body respectively, and the fundus observation was performed by direct ophthalmoscope observation combined with fundus photography, and the retinal routine histopathology HE staining was performed. Analysis of P21, CDK4, Cyclin D1, BAX, BAD, and ABCA4 was used by quantitative RT-PCR and Western blot. Besides, the expression level of ABCA4, AKT, p-AKT, PI3K, p-PI3K, P38, p-P38, JNK, p-JNK, ERK, and p-ERK was detected by Western blot. ResultsAll results indicated that the viability of cells with high expression of ABC4A increased, while the viability of cells with inhibition of ABC4A decreased, the number of cells with high ABC4A expression was significantly higher, and the migration level of cells was significantly reduced after ABC4A inhibition (P < 0.05). ABC4A could affect cell apoptosis by affecting G1/G2 phase. The cell proliferation level was significantly increased with high expression of ABC4A. High expression of ABC4A increased phosphorylation levels, including p-AKT, p-PIK3, and p-P38, while inhibition of ABC4A decreased the expression levels of these proteins (P < 0.05). Inhibition of ABC4A could significantly improve retinopathy, indicating that the proliferation ability of cells was restored after inhibition of ABC4A. ConclusionsOur finding suggested that inhibition of ABC4A ameliorated the injury degree of traumatic PVR and performed the potential anti-PVR effect via inhibiting PI3K/Akt signaling pathway, while promoting cell proliferation in both rabbit and ARPE-19 cells PVR model. The study has a certain innovation by building a traumatic PVR model to explore whether the ABCA4 participates in the regulation of the PI3K/AKT signaling pathway and the pathological mechanism of PVR regulation. At the same time, ABCA4's participation in the regulation of PI3K/Akt signaling pathway can prevent and delay the occurrence and development of PVR, which has positive significance for improving the survival rate and quality of life of patients, and also provides an important basis for its therapeutic mechanism. Therefore, our study demonstrated a significant strategy for inhibiting traumatic PVR via targeting PI3K/Akt/ABCA4 pathway.