Development Of Proliferative Vitreoretinopathy Research Articles

Tenascin-C induces transdifferentiation of retinal pigment epithelial cells in proliferative vitreoretinopathy

Proliferation and transdifferentiation of the retinal pigment epithelium (RPE) are hallmarks of proliferative vitreoretinopathy (PVR); however, the critical regulators of this process remain to be elucidated. Here, we investigated the role of tenascin-C in PVR development. In vitro, exposure of human ARPE-19 (hRPE) cells to TGF-β2 increased tenascin-C expression. Tenascin-C was shown to be involved in TGF-β2-induced transdifferentiation of hRPE cells, which was inhibited by pretreatment with tenascin-C siRNA. In PVR mouse models, a marked increase in the expression of tenascin-C mRNA and protein was observed. Additionally, immunofluorescence analysis demonstrated a dramatic increase in the colocalization of tenascin-C with RPE65 or α-smooth muscle actin(α-SMA) in the epiretinal membranes of patients with PVR. There was also abundant expression of integrin αV and β-catenin in the PVR membranes. ICG-001, a β-catenin inhibitor, efficiently attenuated PVR progression in a PVR animal model. These findings suggest that tenascin-C is secreted by transdifferentiated RPE cells and promotes the development of PVR via the integrin αV and β-catenin pathways. Therefore, tenascin-C could be a potential therapeutic target for the inhibition of epiretinal membrane development associated with PVR.

Knockdown of HSPA13 Inhibits TGFβ1-Induced Epithelial-Mesenchymal Transition of RPE by Suppressing the PI3K/Akt Signaling Pathway.

This study aimed to explore the impact of HSPA13 on epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells and proliferative vitreoretinopathy (PVR) development, along with its associated molecular mechanisms. HSPA13 expression was evaluated in epiretinal membranes (ERMs) from patients with PVR using immunohistochemistry. The effects of HSPA13 knockdown on TGFβ1-induced EMT in hESC-RPE cells were studied through quantitative PCR (qPCR), Western blot, and wound healing assays. Intracellular Ca2+ levels were measured using Fluo-8/AM incubation. A rat PVR model was induced by the intravitreal injection of RPE cells combined with platelet-rich plasma (PRP). RNA-seq was applied to study the molecular mechanism of HSPA13 knockdown-mediated EMT inhibition. HSPA13 was found in human ERMs and its expression increased with TGFβ1 treatment in hESC-RPE cells. Knockdown of HSPA13 inhibited TGFβ1-induced EMT and migration. In the PVR rat model, HSPA13 was expressed in the ERMs and its knockdown in RPE cells reduced the development of PVR. Consistent with these observations, RNA-seq showed a global suppression of TGFβ1-induced EMT and migration by shHSPA13 in RPE cells. Mechanistically, TGFβ1 treatment increased intracellular Ca2+ levels, leading to an upregulation of HSPA13 expression. Downregulation of HSPA13 hindered the phosphorylation of PI3K/Akt in TGFβ1-induced RPE cells. Our study revealed the involvement of HSPA13 in PVR development, as well as in TGFβ1-induced EMT of RPE through the PI3K/Akt signaling pathway. Targeting HSPA13-related pathways involved in regulating EMT in RPE cells could serve as a novel therapeutic approach for patients with PVR.

Nano-Based Drug Approaches to Proliferative Vitreoretinopathy Instead of Standard Vitreoretinal Surgery.

Proliferative vitreoretinopathy (PVR) has traditionally been managed with vitreoretinal surgery. Although there have been several recent innovations in this surgery to make the retinal approach as uninvasive as possible, the outcomes remain unsatisfactory. Significant complications remain and the complexity of the surgical approach is challenging. The focus of this review was to investigate and discuss the effectiveness of nanomedicine, featuring a wide range of drugs and molecules, as a novel potential treatment for PVR. To date, ocular drug delivery remains a significant issue due to the physiological and anatomical barriers, dynamic or static, which prevent the entry of exogenous molecules. We tried to summarize the nanotechnology-based ophthalmic drugs and new nanoparticles currently under research, with the intention of tackling the onset and development of PVR. The purpose of this review was to thoroughly and analytically examine and assess the potential of nano-based techniques as innovative strategies to treat proliferative vitreoretinopathy (PVR). This study aimed to emphasize the breakthroughs in nanomedicine that provide promising therapeutic options to enhance the results of vitreoretinal surgery and halt disease progression, considering the complexity and difficulty of PVR treatment. The future directions of the nanoparticles and nanotherapies applied to PVR highlight the importance of investing in the development of better designs and novel ophthalmic formulations in order to accomplish a mini-invasive ocular approach, replacing the standard-of-care vitreoretinal surgery.

Risk of Proliferative Vitreoretinopathy in the Second Eye in Adult Patients with Bilateral Retinal Detachment

To examine the incidence and risk factors of proliferative vitreoretinopathy (PVR) in the patients who develop rhegmatogenous retinal detachment (RRD) in their fellow eye after having a prior RRD complicated by PVR. Multicenter, retrospective observational study. Eyes with retinal detachment and PVR between 2015 and 2023 were identified through the Vestrum Health Database METHODS: Risk factors for PVR development, specifically documented PVR in the fellow eye, gender, age, lens status, and presenting and final visual acuity, were evaluated. Odds ratio for PVR development during 6 months post-operative period. Of 57,264 patients, 11% had PVR in at least one eye. Of the 50,989 patients who did not develop PVR after the initial RRD, 4,834 developed RRD in the fellow eye. 166 of these patients developed PVR in their second eye for a PVR rate of 3% in the fellow eye. Of the 6,275 patients who developed PVR after primary RRD repair, 406 of these patients went on to develop RRD in their fellow eye. 42 of these patients developed PVR in their second eye for a PVR rate of 10%. A regression model that also included age, gender and visual acuity led to an odds ratio of 3.42 (p<0.001). The odds ratio of PVR development generally decreased with age. Pseudophakic patients had a higher odds ratio for PVR development, 1.48 (p=0.017). Initial patients with VA 20/40-20/80 had an odds ratio of 2.15 (p=0.003). Patients with VA worse than 20/200 had an odds ratio of 2.89 for PVR development (p<0.001). Patients with a history RRD with PVR in one eye, have approximately 3.5 times higher rate of PVR in their second eye after RRD compared with patients without a history of PVR. This finding potential impacts surgical decisions and use of prophylactic anti-PVR therapy if the patient's second eye has RRD. The final visual acuity in second eye of patients with history PVR is better than for the second eye of patients with no history of PVR which may indicate surgeons are already taking steps to prevent PVR in the patient's second eye.

Epithelial-mesenchymal Transition (EMT) and the Effect of Atorvastatin on it in ARPE-19 cells

Proliferative vitreoretinopathy (PVR) develops after an unsuccessful or complicated recovery from rhegmatogenous retinal detachment (RRD) surgery. Intraocular scar formation with the contribution of epithelial-mesenchymal transition (EMT) in RPE cells is prominent in the pathology of PVR. In the present study, the EMT process was experimentally induced in human retinal pigment epithelium (RPE; ARPE-19) cells, and the effect of atorvastatin on the process was studied. The mRNA and protein levels of mesenchymal markers actin alpha 2 (ACTA2) / alpha-smooth muscle actin (α-SMA) and fibronectin (FN), and epithelial markers occludin (OCLN) and zonula occludens-1 (ZO-1) were measured using quantitative real-time PCR (qRT-PCR) and western blot methods, respectively. In addition, α-SMA and FN were visualized using immunofluorescence staining. Cells were photographed under a phase contrast light microscope. Changes in the functionality of cells following the EMT process were studied using the IncuCyte scratch wound cell migration assay and the collagen cell invasion assay with confocal microscopy. The induction of EMT in ARPE-19 cells increased the expression of mesenchymal markers ACTA2/α-SMA and fibronectin and reduced the expression of epithelial marker OCLN both at mRNA and protein levels. The mRNA levels of ZO-1 were lower after EMT, as well. Increased levels of α-SMA and FN were confirmed by immunofluorescence staining. Atorvastatin further increased the mRNA levels of mesenchymal markers ACTA2 and FN as well as the protein levels of α-SMA and reduced the mRNA levels of epithelial markers OCLN and ZO-1 under the EMT process. EMT promoted wound closure and cell invasion into the 3D collagen matrix when compared to untreated control cells. These data present cellular changes upon the induction of the EMT process in ARPE-19 cells and the propensity of atorvastatin to complement the effect. More studies are needed to confirm the exact influence of the EMT process and atorvastatin treatment on the PVR development after RRD surgery.

Retinal pigment epithelial cell culture

Objective: Retinal pigment epithelial cells (RPEs), as the main cellular component of the preretinal membrane, whose excessive proliferation can lead to the development of proliferative vitreoretinopathy as interaction with other cellular components and intercellular substance. Here, we developed an effective method to culture RPEs so as to provide effective cell source for later experimental usage. Methods: The harvested of eye cup that retains the retinal pigment epithelium was gently washed three times with phosphate buffered saline (PBS), and was added with 0.02 mg/ml dispase enzyme, which was cut into small pieces and then placed in the incubator for digestion for about half an hour. Subsequently, gently blowing was performed multiple times to detach the RPEs from the retina to collect the RPEs suspension. After implantation into the culture dish, when the cells were grown and covered with 80-90% of the bottom of the bottle, digestion of the cells is carried out with 0.25% trypsin. After removing them from the wall, the digested cell suspension was collected, followed by addition of Dulbecco's modified Eagle medium/Nutrient Mixture F-12 (DMEM/F12) to stop digestion. The mixture was subject to centrifuge at 1000 r/min for 8 min, with the supernatant discarded, and then the cells located in bottom were passaged at 1:3 ratios. During the process, the morphology and viability were observed and cell identification were also performed. Results: Primary cultured cells began to adhere to the wall at 4 h, characterized with a flat and polygonal morphology, rich in pigment particles. On 3 days, there was a significant increase in cell numbers accompanied by cluster formation, resulting in a stabilized cobblestone-like appearance. By 5 days, cells elongated and formed dense clusters. Growth curve analysis revealed robust proliferation at 3 and 5 days. Immunofluorescence staining confirmed that over 90% of the cells were positive for RPE-65, indicating successful isolation and culture of pure rat RPEs. Conclusions: The RPEs cultured by the above method are in good growth and it can be used for further experimental studies.

Effect of Oral Prednisone on the Prevention and Management of Proliferative Vitreoretinopathy After Open-Globe Injury.

Purpose: To determine the impact of oral prednisone on the final visual acuity (VA) and prevention of proliferative vitreoretinopathy (PVR) in patients having pars plana vitrectomy (PPV) for globe injuries. Methods: A retrospective chart review was performed of all globe injuries with an initial repair and subsequent PPV between 2009 and 2018. Data included the initial VA, zones of injury, initial closure date, time to secondary intervention (PPV), oral prednisone (1 mg/kg/day) use, the final VA, and enucleation rate. Multivariable regression models were used to assess the impact of oral prednisone use on anatomic and functional outcomes. Results: The mean (±SD) patient age was 46.25 ±18.56 years (range, 13-92); 131 (83.9%) were men. Oral prednisone intake was recorded in 81 patients (52.3%). The prednisone group had significantly more zone 3 involvement (P = .001), worse initial VA (2.28 vs 1.92 logMAR; P = .003), and a greater mean number of surgeries (P = .020) than the no-steroids (control) group but an equivalent final logMAR VA (1.57 vs 1.52; P = .881). The prednisone group had significant VA improvement (P = .025); however, oral prednisone use did not predict the development of PVR (29.23% vs 12.90%; odds ratio [OR], 2.81; 95% CI, 0.89-8.85) or retinal detachment (27.27% vs 29.58%; OR, 0.59; 95% CI, 0.23-1.56). Conclusions: Despite a worse initial clinical presentation, patients who received oral prednisone had significant visual improvement compared with the control group. However, oral prednisone (1 mg/kg/day) use at the time of injury did not decrease the PVR rate.

Exosomes-based dual drug-loaded nanocarrier for targeted and multiple proliferative vitreoretinopathy therapy.

Proliferative vitreoretinopathy (PVR) is a common cause of vision loss after retinal reattachment surgery and ocular trauma. The key pathogenic mechanisms of PVR development include the proliferation, migration and epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPEs) activated by the growth factors and cytokines after surgery. Although some drugs have been tried in PVR treatments as basic investigations, the limited efficacy remains an obstacle, which may be due to the single pharmacological action and lack of targeting. Herein, the anti-proliferative Daunorubicin and anti-inflammatory Dexamethasone were co-loaded in the RPEs-derived exosomes (Exos), obtaining an Exos-based dual drug-loaded nanocarrier (Exos@D-D), and used for multiple PVR therapy. Owing to the advantages of homologous Exos and the dual drug loading, Exos@D-D showed good RPEs targeting as well as improved uptake efficiency, and could inhibit the proliferation, migration, as well as EMT of RPEs effectively. The animal studies have also demonstrated that Exos@D-D effectively inhibits the production of proliferative membranes and prevents the further development of inflammation, shows significant therapeutic effects on PVR and good biocompatibility. Such Exos-based dual drug-loaded nanocarrier investigation not only provides a promising approach for multifunctional exosome drug delivery systems construction, but also has great potential in PVR clinical therapy application.

Role of Intrasilicon Oil Methotrexate Injection to Prevent Development of Proliferative Vitreoretinopathy

Purpose: To determine the role of intra-silicon oil methotrexate injection to prevent Proliferative Vitreoretinopathy. Study Design: Quasi experimental Study. Place and Duration: Ophthalmology department of Sahiwal Teaching Hospital, Sahiwal from February 2022 to August 2022. Methods: Study included patients of either gender, older than 19 years with rhegmatogenous retinal detachment with Proliferative vitreoretinopathy (PVR) grade B or less. There were two groups and each group had fifty-one patients. All patients underwent pars plana vitrectomy and silicon oil tamponade. Group 1 was control group. Group 2 had intravitreal injections of methotrexate 500mg at the end of surgery. We repeated the injections at 1st, 2nd, and 4th week postoperatively. Results: There were 56 (54.9%) male and 46 (45.1%) female patients. Postoperatively visual acuity improved in thirty cases (58.82%) in group 1 and in forty-two cases (82.35%) in group 2. Postoperatively PVR developed in 11 (21.57%) patients in group 1 while in group 2 no patient had PVR. Recurrent Retinal detachment occurred in 9 (19.61%) patients in group 1 and 3 (5.88%) patients in group 2. Chi square test demonstrated statistically significant difference in the frequency of development of PVR and re-detachment of retina between two groups, p&lt;0.05. Conclusion: Methotrexate is an effective adjuvant used in Pars plana Vitrectomy for rhegmatogenous retinal detachment repair. It prevents Proliferative vitreoretinopathy resulting in better surgical and functional outcome.

Effect of Oral Riboflavin and Direct-sun UV-A on Tumor Necrosis Factor Alpha (TNF-α) Concentrations in Tears of Mild-Moderate Keratoconus Patients

Purpose: To determine the role of intra-silicon oil methotrexate injection to prevent Proliferative Vitreoretinopathy. Study Design: Quasi experimental Study. Place and Duration: Ophthalmology department of Sahiwal Teaching Hospital, Sahiwal from February 2022 to August 2022. Methods: Study included patients of either gender, older than 19 years with rhegmatogenous retinal detachment with Proliferative vitreoretinopathy (PVR) grade B or less. There were two groups and each group had fifty-one patients. All patients underwent pars plana vitrectomy and silicon oil tamponade. Group 1 was control group. Group 2 had intravitreal injections of methotrexate 500mg at the end of surgery. We repeated the injections at 1st, 2nd, and 4th week postoperatively. Results: There were 56 (54.9%) male and 46 (45.1%) female patients. Postoperatively visual acuity improved in thirty cases (58.82%) in group 1 and in forty-two cases (82.35%) in group 2. Postoperatively PVR developed in 11 (21.57%) patients in group 1 while in group 2 no patient had PVR. Recurrent Retinal detachment occurred in 9 (19.61%) patients in group 1 and 3 (5.88%) patients in group 2. Chi square test demonstrated statistically significant difference in the frequency of development of PVR and re-detachment of retina between two groups, p&lt;0.05. Conclusion: Methotrexate is an effective adjuvant used in Pars plana Vitrectomy for rhegmatogenous retinal detachment repair. It prevents Proliferative vitreoretinopathy resulting in better surgical and functional outcome.

The Effect of Anti-Autotaxin Aptamers on the Development of Proliferative Vitreoretinopathy.

This study investigated the effect of anti-autotaxin (ATX) aptamers on the development of proliferative vitreoretinopathy (PVR) in both in vivo and in vitro PVR swine models. For the in vitro study, primary retinal pigment epithelial (RPE) cells were obtained from porcine eyes and cultured for cell proliferation and migration assays. For the in vivo study, a swine PVR model was established by inducing retinal detachment and injecting cultured RPE cells (2.0 × 106). Concurrently, 1 week after RPE cell injection, the anti-ATX aptamer, RBM-006 (10 mg/mL, 0.1 mL), was injected twice into the vitreous cavity. Post-injection effects of the anti-ATX aptamer on PVR development in the in vivo swine PVR model were investigated. For the in vitro evaluation, the cultured RPE cell proliferation and migration were significantly reduced at anti-ATX aptamer concentrations of 0.5-0.05 mg and at only 0.5 mg, respectively. Intravitreal administration of the anti-ATX aptamer also prevented tractional retinal detachment caused by PVR in the in vivo PVR model. We observed that the anti-ATX aptamer, RBM-006, inhibited PVR-related RPE cell proliferation and migration in vitro and inhibited the progression of PVR in the in vivo model, suggesting that the anti-ATX aptamer may be effective in preventing PVR.

Ligand-independent activation of platelet-derived growth factor receptor β promotes vitreous-induced contraction of retinal pigment epithelial cells

BackgroundEpiretinal membranes in patients with proliferative vitreoretinopathy (PVR) consist of extracellular matrix and a number of cell types including retinal pigment epithelial (RPE) cells and fibroblasts, whose contraction causes retinal detachment. In RPE cells depletion of platelet-derived growth factor (PDGF) receptor (PDGFR)β suppresses vitreous-induced Akt activation, whereas in fibroblasts Akt activation through indirect activation of PDGFRα by growth factors outside the PDGF family (non-PDGFs) plays an essential role in experimental PVR. Whether non-PDGFs in the vitreous, however, were also able to activate PDGFRβ in RPE cells remained elusive.MethodsThe CRISPR/Cas9 technology was utilized to edit a genomic PDGFRB locus in RPE cells derived from an epiretinal membrane (RPEM) from a patient with PVR, and a retroviral vector was used to express a truncated PDGFRβ short of a PDGF-binding domain in the RPEM cells lacking PDGFRβ. Western blot was employed to analyze expression of PDGFRβ and α-smooth muscle actin, and signaling events (p-PDGFRβ and p-Akt). Cellular assays (proliferation, migration and contraction) were also applied in this study.ResultsExpression of a truncated PDGFRβ lacking a PDGF-binding domain in the RPEM cells whose PDGFRB gene has been silent using the CRISPR/Cas9 technology restores vitreous-induced Akt activation as well as cell proliferation, epithelial-mesenchymal transition, migration and contraction. In addition, we show that scavenging reactive oxygen species (ROS) with N-acetyl-cysteine and inhibiting Src family kinases (SFKs) with their specific inhibitor SU6656 blunt the vitreous-induced activation of the truncated PDGFRβ and Akt as well as the cellular events related to the PVR pathogenesis. These discoveries suggest that in RPE cells PDGFRβ can be activated indirectly by non-PDGFs in the vitreous via an intracellular pathway of ROS/SFKs to facilitate the development of PVR, thereby providing novel opportunities for PVR therapeutics.ConclusionThe data shown here will improve our understanding of the mechanism by which PDGFRβ can be activated by non-PDGFs in the vitreous via an intracellular route of ROS/SFKs and provide a conceptual foundation for preventing PVR by inhibiting PDGFRβ transactivation (ligand-independent activation).

Clinical efficacy of early vitrectomy in patients with severe blunt ocular trauma

BACKGROUND: Eye injury is an actual problem, occupying a leading position among the main causes of blindness and low vision, accounting for 22.8% in the structure of primary visual disability, of which 53% of cases are due to closed eye injury. Despite the development and widespread introduction into practice of methods of high-tech care for patients of this profile, there are a number of complications that poorly respond to treatment, ultimately leading to the loss of visual function of the injured eye.&#x0D; AIM: Evaluation of the effectiveness of early vitrectomy in patients with severe blunt ocular trauma, based on clinical results obtained during treatment and postoperative follow-up.&#x0D; MATERIALS AND METHODS: The study included 34 patients (34 eyes) with contusion-type eye injury. The mean age of patients was 39 years, among them 30 were men (88.24%) and 4 (11.76%) women. Patients were divided into 2 groups. Group 1 included 11 patients (10 men, 1 woman) with an open-type eye injury with a subconjunctival scleral rupture; upon admission, visual acuity varied from incorrect light projection to 0.01. In group 2, there were 23 patients (20 men, 3 women) with severe closed eye injury, upon admission to the hospital, visual acuity ranged from incorrect light projection to 0.06. In all cases, patients underwent subtotal three-port vitrectomy at an early date (up to 3 days) after injury.&#x0D; RESULTS: On the 1st day after surgery, there was an improvement in visual acuity in all patients. The follow-up period for patients was 6 months. All included patients had a stable anatomical result, no cases of subatrophy were noted, satisfactory functional results were achieved - visual acuity varied from 0.02 to 0.8. After 6 months, 32 out of 34 eyes (94.12%) showed no signs of proliferative vitreoretinopathy. In 2 patients (18.18%) from group 1, the development of proliferative vitreoretinopathy under silicone oil was revealed. Epiretinal membrane was diagnosed in 2 patients (8.7%) from group 2 and in 1 patient (9.09%) from group 1.&#x0D; CONCLUSIONS: Obtained clinical results of treatment of patients with severe blunt ocular trauma indicate the expediency of vitrectomy in early stages after injury, which is an effective treatment method. Long-term results demonstrate stable functional results for 6 months. Vitrectomy performed early after injury serves for prevention of proliferative vitreoretinopathy, but does not completely exclude its development. Performing surgery early after injury increases the prospects for preserving visual functions of the eye and is a positive prognostic factor.

Orbital Lesion as the Initial Manifestation of a Neuroendocrine Tumour

Laser flare photometry provides a non-invasive and objective measurement of the Tyndall effect in the anterior chamber. The laser flare value (measured in photon number per millisecond [pc/ms]) thus quantifies the extent of disruption to the blood-aqueous barrier and can be used in clinical applications to monitor uveitis therapy or to measure the postoperative degree of inflammation. Standardised performance must be observed during measurement. Publications of the last 35years on laser flare photometry deal not only with the measurement procedure but also with its use in clinical practice for different ophthalmological pathologies. Likewise, various influencing factors have already been investigated and described that must be considered when measuring and evaluating laser flare values. The focus of this article is the relevance of laser flare photometry in retinal pathologies. In recently published studies, the level of objective tyndallometry in primary rhegmatogenous retinal detachment is shown to depend on lens status, symptom duration, and extent of retinal detachment. The greater is the area of the retina affected, the greater the disruption of the blood-aqueous barrier appears to be. Elevated laser flare values have also been considered as a predictor for the development of proliferative vitreoretinopathy (PVR). However, based on current knowledge, this assumption must be put into perspective. According to current data, objective tyndallometry can be used to monitor the progression of intraocular inflammation and to quantify the blood-aqueous barrier, and the values correlate with the extent and anatomical features, as well as the symptom duration in retinal detachment. Many influencing factors have already been identified. But further evaluation is desirable and needed. It is still unclear whether laser flare values can be used in the future as a predictor for sequelae such as PVR development.

Proliferative Vitreoretinopathy Following Transscleral Diode Cyclophotocoagulation.

Transscleral diode laser cyclophotocoagulation may trigger the development of proliferative vitreoretinopathy. Our article demonstrates one such case leading to tractional macula off retinal detachment in a child with aphakic glaucoma. The purpose of this article is to describe a case of proliferative vitreoretinopathy (PVR) developing subsequent to transscleral diode laser cyclophotocoagulation (cyclodiode) in a pediatric patient with aphakic glaucoma. PVR most commonly occurs following rhegmatogenous retinal detachment (RRD) repair however, to the best of our knowledge, has never been reported to appear after cyclodiode. Retrospective evaluation of case presentation and intraoperative findings. A 13-year-old girl with aphakic glaucoma presented four months after cyclodiode of the right eye with a retrolental fibrovascular membrane and anterior PVR. The PVR extended posteriorly over the next month after which the patient developed a tractional macula off retinal detachment. Pars Plana vitrectomy was performed confirming dense anterior and posterior PVR. Review of the literature suggests an inflammatory cascade, similar to that seen in PVR development following RRD, may occur from the destruction of the ciliary body by cyclodiode. As a result, fibrous transformation may occur, likely accounting for the cause of PVR development in this case. The pathophysiology of PVR development remains unclear. This case demonstrates that PVR may occur following cyclodiode and should be considered during post-operative monitoring after this procedure.

Safety and efficacy of cryopexy during pars Plana vitrectomy in rhegmatogenous retinal detachment.

To evaluate efficacy and safety of intraoperative cryoretinopexy in cases of rhegmatogenous retinal detachment (RRD). In this retrospective, interventional case series, we review the medical records of 85 consecutive cases of RRD treated with pars plana vitrectomy and gas tamponade, without the use of perfluorocarbon liquids. Baseline best-corrected visual acuity, intraocular pressure, number and location of retinal breaks, location and extension of retinal detachment, duration of symptoms, macula status, presence, and grade of proliferative vitreoretinopathy (PVR) were registered. Follow-up visits were at 1 day, 15 days, 1 month and 3 months. Anatomical and functional outcomes and any adverse event were recorded. Primary anatomical success was obtained in 82/85 patients (96%). During the postoperative period, PVR was observed in 4/85 cases (4.7%), 3 of whom developed recurrence of retinal detachment. 7/85 (8.2%) patients developed ocular hypertension. We built a model of logistic regression including age, sex, lens status, macula status, number of quadrants involved, number of ruptures and duration of symptoms. None of the variables considered was found to be a predictor of postoperative PVR development. Symptom's duration (β = 0.429; 95% CI = 0.009-0.023; P < 0.001) and preoperative BCVA (β = 0.273; 95% CI = 0.034-0.184; P = 0.005) were predictors for final BCVA. These findings emphasize the safety and efficacy of the use of intraoperative cryotherapy, associated with PPV and gas tamponade, for the management of uncomplicated RRDs.

Inflammation and Oxidative Stress Gene Variability in Retinal Detachment Patients with and without Proliferative Vitreoretinopathy.

This study investigated the association between certain genetic variations and the risk of developing proliferative vitreoretinopathy (PVR) after surgery. The study was conducted on 192 patients with primary rhegmatogenous retinal detachment (RRD) who underwent 3-port pars plana vitrectomy (PPV). The distribution of single nucleotide polymorphisms (SNPs) located in genes involved in inflammation and oxidative stress associated with PVR pathways were analyzed among patients with and without postoperative PVR grade C1 or higher. A total of 7 defined SNPs of 5 genes were selected for genotyping: rs4880 (SOD2); rs1001179 (CAT); rs1050450 (GPX1); rs1143623, rs16944, rs1071676 (IL1B); rs2910164 (MIR146A) using competitive allele-specific polymerase chain reaction. The association of SNPs with PVR risk was evaluated using logistic regression. Furthermore, the possible association of SNPs with postoperative clinical parameters was evaluated using non-parametric tests. The difference between two genotype frequencies between patients with or without PVR grade C1 or higher was found to be statistically significant: SOD2 rs4880 and IL1B rs1071676. Carriers of at least one polymorphic IL1B rs1071676 GG allele appeared to have better postoperative best-corrected visual acuity only in patients without PVR (p = 0.070). Our study suggests that certain genetic variations may play a role in the development of PVR after surgery. These findings may have important implications for identifying patients at higher risk for PVR and developing new treatments.

Ligand-Independent Activation of Platelet-Derived Growth Factor Receptor β Promotes Contraction of Retinal Pigment Epithelial Cells

Background: Epiretinal membranes in patients with Proliferative Vitreoretinopathy (PVR) consist of extracellular matrix and a number of cell types including Retinal Pigment Epithelial (RPE) cells and fibroblasts, whose contraction causes retinal detachment. In RPE cells depletion of Platelet-Derived Growth Factor (PDGF) receptor (PDGFR) β suppresses vitreous-induced Akt activation, where as in fibroblasts Akt activation through indirect activation of PDGFRa by growth factors outside the PDGF family (non-PDGFs) plays an essential role in experimental PVR. Whether non-PDGFs in the vitreous, however, were also able to activate PDGFRβ in RPE cells remained elusive. Methods: We showed that expression of a truncated PDGFRβ lacking a PDGF-binding domain in the RPE cells whose PDGFRB gene had been silent using the CRISPR/Cas9 technology restored vitreous-induced Akt activation as well as cell proliferation, epithelial-mesenchymal transition, migration and contraction. Results: We found that scavenging Reactive Oxygen Species (ROS) with N-acetyl-cysteine and inhibiting Src Family Kinases (SFKs) with their specific inhibitor SU6656 blunted the vitreous-induced activation of the truncated PDGFRβ and Akt as well as the cellular events related to the PVR pathogenesis. Conclusions: These discoveries suggest that in RPE cells PDGFRβ can be activated indirectly by non-PDGFs in the vitreous via an intracellular pathway of ROS/SFKs to facilitate the development of PVR, thereby providing novel opportunities for PVR therapeutics.

MicroRNA Expression in Subretinal Fluid in Eyes Affected by Rhegmatogenous Retinal Detachment.

Proliferative vitreoretinopathy (PVR) is an abnormal intraocular scarring process that can complicate cases of rhegmatogenous retinal detachment (RRD). Although previous studies have examined the relevance of microRNAs (miRNAs) in ophthalmic diseases, only a few studies have evaluated the expression profiles of microRNAs in subretinal fluid. We hypothesized that the expression profiles of specific miRNAs may change in response to RRD, in the subretinal fluid that is directly in contact with photoreceptors and the retinal pigment epithelium (RPE). We looked for a potential correlation between the expression of specific miRNAs in eyes with RRD and known clinical risk factors of PVR. A total of 24 patients (59 ± 11 years) who underwent scleral buckling procedure were enrolled in this prospective study. Twenty-four undiluted subretinal fluid samples were collected, RNA was isolated and qRT-PCR was performed to analyze the expression of 12 miRNAs. We found the existence of a positive association between the expression of miR-21 (p = 0.017, r = 0.515) and miR-34 (p = 0.030, r = 0.624) and the duration of symptoms related to retinal detachment. Moreover, the expression of miR-146a tended to decrease in patients who developed PVR. Subretinal fluid constitutes an intriguing biological matrix to evaluate the role of miRNAs leading to the development of PVR.

Intravitreal slow-release dexamethasone alleviates traumatic proliferative vitreoretinopathy by inhibiting persistent inflammation and Müller cell gliosis in rabbits.

To evaluate the effects of intravitreal slow-release dexamethasone on traumatic proliferative vitreoretinopathy (PVR) and Müller cell gliosis and preliminarily explored the possible inflammatory mechanism in a rabbit model induced by penetrating ocular trauma. Traumatic PVR was induced in the right eyes of pigmented rabbits by performing an 8-mm circumferential scleral incision placed 2.5 mm behind the limbus, followed by treatment with a slow-release dexamethasone implant (Ozurdex) or sham injection. Left eyes were used as normal controls. The intraocular pressure (IOP) was monitored using an iCare tonometer. PVR severity was evaluated via anatomical and histopathological examinations every week for 6wk; specific inflammatory cytokine and proliferative marker levels were measured by quantitative real-time polymerase chain reaction, Western blot, protein chip analysis, or immunofluorescence staining. During the observation period, PVR severity gradually increased. Intense Müller cell gliosis was observed in the peripheral retina near the wound and in the whole retina of PVR group. Ozurdex significantly alleviated PVR development and Müller cell gliosis. Post-traumatic inflammation fluctuated and was persistent. The interleukin-1β (IL-1β) mRNA level was significantly upregulated, peaking on day 3 and increasing again on day 21 after injury. The expression of nod-like receptor family pyrin domain containing 3 (NLRP3) showed a similar trend that began earlier than that of IL-1β expression. Ozurdex suppressed the expression of IL-1β, NLRP3, and phosphorylated nuclear factor-kappa B (NF-κB). The average IOP after treatment was within normal limits. The present study demonstrates chronic and fluctuating inflammation in a traumatic PVR rabbit model over 6wk. Ozurdex treatment significantly inhibites inflammatory cytokines expression and Müller cell gliosis, and thus alleviates PVR severity. This study highlights the important role of IL-1β, and Ozurdex inhibites inflammation presumably via the NF-κB/NLRP3/IL-1β inflammatory axis. In summary, Ozurdex provides a potential therapeutic option for traumatic PVR.