Preserving posterior capsular integrity in post-endothelial keratoplasty posterior capsular opacification.
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ABSTRACT:
SUBMITTER: Titiyal JS
PROVIDER: S-EPMC8597509 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Fibrotic posterior capsular opacification (PCO), a major complication of cataract surgery, is driven by transforming growth factor-β (TGF-β). Previously, αV integrins were found to be critical for the onset of TGF-β-mediated PCO in vivo; however, the functional heterodimer was unknown. Here, β8 integrin-conditional knockout (β8ITG-cKO) lens epithelial cells (LCs) attenuated their fibrotic responses, while both β5 and β6 integrin-null LCs underwent fibrotic changes similar to WT at 5 days post cataract surgery (PCS). RNA-Seq revealed that β8ITG-cKO LCs attenuated their upregulation of integrins and their ligands, as well as known targets of TGF-β-induced signaling, at 24 hours PCS. Treatment of β8ITG-cKO eyes with active TGF-β1 at the time of surgery rescued the fibrotic response. Treatment of WT mice with an anti-αVβ8 integrin function blocking antibody at the time of surgery ameliorated both canonical TGF-β signaling and LC fibrotic response PCS, and treatment at 5 days PCS, after surgically induced fibrotic responses were established, largely reversed this fibrotic response. These data suggest that αVβ8 integrin is a major regulator of TGF-β activation by LCs PCS and that therapeutics targeting αVβ8 integrin could be effective for fibrotic PCO prevention and treatment.
| S-EPMC8663568 | biostudies-literature
Project description:Fibrotic posterior capsular opacification (PCO), one of the major complications of cataract surgery, occurs when lens epithelial cells (LCs) left behind post cataract surgery (PCS) undergo epithelial to mesenchymal transition, migrate into the optical axis and produce opaque scar tissue. LCs left behind PCS robustly produce fibronectin, although its roles in fibrotic PCO are not known. In order to determine the function of fibronectin in PCO pathogenesis, we created mice lacking the fibronectin gene (FN conditional knock out -FNcKO) from the lens. While animals from this line have normal lenses, upon lens fiber cell removal which models cataract surgery, FNcKO LCs exhibit a greatly attenuated fibrotic response from 3 days PCS onward as assessed by a reduction in surgery-induced cell proliferation, and fibrotic extracellular matrix (ECM) production and deposition. This is correlated with less upregulation of Transforming Growth Factor β (TGFβ) and integrin signaling in FNcKO LCs PCS concomitant with sustained Bone Morphogenetic Protein (BMP) signaling and elevation of the epithelial cell marker E cadherin. Although the initial fibrotic response of FNcKO LCs was qualitatively normal at 48 h PCS as measured by the upregulation of fibrotic marker protein αSMA, RNA sequencing revealed that the fibrotic response was already quantitatively attenuated at this time, as measured by the upregulation of mRNAs encoding molecules that control, and are controlled by, TGFβ signaling, including many known markers of fibrosis. Most notably, gremlin-1, a known regulator of TGFβ superfamily signaling, was upregulated sharply in WT LCs PCS, while this response was attenuated in FNcKO LCs. As exogenous administration of either active TGFβ1 or gremlin-1 to FNcKO lens capsular bags rescued the attenuated fibrotic response of fibronectin null LCs PCS including the loss of SMAD2/3 phosphorylation, this suggests that fibronectin plays multifunctional roles in fibrotic PCO development.
| S-EPMC7321929 | biostudies-literature
Project description:Objective: The present study was conducted to determine the role of gremlin during the development of posterior capsular opacification (PCO) via in vitro and in vivo experiments. Methods: The activation, roles and relationships of the BMPs/Smad1/5, MAPK, FAK and AKT signaling pathways in human lens epithelial cells (HLECs) after gremlin induction were detected by western blotting and real-time PCR. Wound-healing, transwell, capsular bag models and rat PCO models assays were used to test the effects of gremlin on HLECs' migration, proliferation, EMT-specific protein α-smooth muscle actin（α-SMA）and development of PCO in rats. Results: Our data showed that knockdown of the gremlin inhibited the development of PCO and reduced expression of α-SMA in rats. While gremlin did not alter the migration of HLECs, it increased the expression of p-ERK and p-AKT. Knockout of Smad2 or Smad3 inhibited the expression of p-ERK and p-AKT proteins induced by gremlin. Gremlin also reduced BMP4-induced expression of the p-Smad1/5 protein. Finally, knockout of Smad1/5 increased gremlin-induced expression of α-SMA, fibronectin and type I collagen (COL-1) in HLECs. Conclusion: These results suggested that gremlin contributed to the development of PCO by promoting LEC proliferation, activation of TGF-β/Smad, ERK and AKT signaling and inhibition of BMPs/Smad1/5 signaling. Furthermore, inhibiting gremlin effectively impaired both PCO development in rats and EMT in the lens capsule. Thus, our data suggest that gremlin might be a potential target for PCO.
| S-EPMC6649605 | biostudies-literature
Project description:PurposeThe purpose of this study was to evaluate the effect of aldose reductase (AR) inhibition on posterior capsular opacification (PCO) with the use of a pig eye capsular bag model.MethodsPig eye capsular bags were prepared by capsulorhexis and cultured in medium without or with AR inhibitors for 7 days. Immunostaining was performed in paraformaldehyde-fixed capsular bags to determine the expression of proliferating cell nuclear antigen (PCNA), alpha-smooth muscle actin (SMA), beta-crystallin, and intercellular adhesion molecule (ICAM)-1. The effect of AR inhibition on basic fibroblast growth factor (BFGF)-induced mitogenic signaling in cultured human lens epithelial cells (HLECs) was examined. Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell counting, the expression of alpha-SMA, beta-crystallin, and ICAM-1 by Western blot and immunocytochemical analysis, protein kinases by Western blot analysis, and NF-kappaB activation by gel shift and reporter assays.ResultsDuring culture of pig eye capsular bags, residual cells on both the anterior and the posterior capsule showed vigorous growth. Treatment with AR inhibitors significantly prevented the lens epithelial cell growth in capsular bags and expression of alpha-SMA, beta-crystallin, and ICAM-1. HLECs showed a dose-dependent response to BFGF, proliferation at lower concentrations (<20 ng/mL) and differentiation/transdifferentiation at higher concentrations (>50 ng/mL). Inhibition of AR also prevented the BFGF-induced activation of ERK1/2, JNK, and NF-kappaB in HLECs.ConclusionsResults suggest that AR is required for lens epithelial cell growth and differentiation/transdifferentiation in the capsular bags, indicating that inhibition of AR could be a potential therapeutic target in the prevention of PCO.
| S-EPMC2832582 | biostudies-literature
Project description:PurposeTo evaluate a new technique of posterior capsulorhexis using air support to treat primary posterior capsular opacification (PCO) during cataract extraction surgery or to prevent postoperative PCO.Setting(1) Ophthalmology department, Faculty of Medicine, Minia University, 61519, El-Minia, Egypt. (2) Security Forces Hospital, Ophthalmology Department, Riyadh, Kingdom of Saudi Arabia.DesignProspective, randomized, consecutive case comparative non controlled study.MethodsOne hundred eyes of 100 patients with a mean age of 63.3 years with dense cataract were enrolled in the study. Fifty of them (group (1)) were with primary PCO (discovered during the operations) and fifty (group (2)) with clear posterior capsule. All of the patients underwent phacoemulsification and posterior capsulorhexis using the air to support the posterior capsule. Then, IOL implantations were done between the anterior and posterior capsular rims. Postoperatively, each patient was evaluated for the following: visual acuity (UCVA and BCVA), manifest refractive spherical equivalent (MRSE), intraocular pressure, intraocular lens (IOL) stability, visual axis opacification, and posterior segment complications as retinal breaks, retinal detachment, or cystoid macular edema (CME).ResultsThere were no significant differences in UCVA, BCVA, and MRSE. All cases had a clear visual axis, with stable IOL and normal IOP during the follow-up period without posterior segment complications. The VA improved significantly throughout the follow-up periods in both groups without significant clinical difference.ConclusionPneumatic posterior capsulorhexis is a new effective technique for the treatment of primary PCO in dense cataract and for prevention of postoperative PCO with the good visual outcomes and minimal complications. This trial is registered with NCT04007965.
| S-EPMC6948290 | biostudies-literature
Project description:AimTo evaluate the incidence of postoperative posterior capsular striae (PCS) and its influence on posterior capsular opacification (PCO) in patients implanted with two types of lens material.SettingTertiary eye care center in central rural India.Study designA prospective, observational, nonrandomized study.Materials and methodsThe study included 1247 patients having age-related cataract scheduled for removal by phacoemulsification technique and implantation of hydrophilic or hydrophobic intraocular lens (IOL). Demographic profile, nuclear grading, axial length, and IOL power were noted. Details of PCS were noted on the 1st postoperative day in patients with clear cornea. Postoperative follow-up was ensured to study the status of PCS and development of PCO.ResultsThe overall incidence of PCS was 19.8% (247 out of 1247 eyes). Out of 1247 patients, 641 patients (51.4%) had hydrophilic IOL implantation and 201 eyes had PCS (31.4%) and 606 patients (48.6%) had hydrophobic IOL implantation and 46 eyes had PCS (7.6%), P = 0.04. Three and more striae were seen in 119 eyes (119/641, 18.6%) in hydrophilic group and 4 eyes (4/606, 0.66%) in hydrophobic group. Sixty-two eyes (62/201, 30.9%) in hydrophilic group with multiple PCS were reported with persistent striae after 6 months of surgery. Two eyes in hydrophobic group had persistent striae even after 3 years of follow-up. Evaluation of PCO score of the hydrophilic group was 0.6 whereas of the hydrophobic group was 0.1 (P = 0.04). Ten patients of the hydrophilic group only required neodymium-doped yttrium aluminum garnet (ND: YAG) laser capsulotomy.ConclusionThe incidence of PCS was higher in hydrophilic than hydrophobic IOLs. Multiple PCS persisting in patients beyond 6 months after operation should be followed up for early development of PCO, particularly in patients implanted with hydrophilic IOL.
| S-EPMC5508456 | biostudies-literature
Project description:PurposeTo study the effect of rotation of intraocular lens (IOL) on posterior capsular opacification (PCO) in eyes with phacoemulsification.MethodsThis was a prospective, comparative, randomized case series. One eye of each patient was randomized to one of two groups. The 360-degree rotation of IOL was carried out after its placement in the capsular bag (rotation group). The control group had no rotation of IOL. PCO was analyzed by an independent observer on EPCO computer analysis system at 6, 12, 24, and 36 months.ResultsThe study included 50 patients (100 eyes) with senile cataracts scheduled for phacoemulsification and IOL implantation. The median age in 2 groups was 66 years. 25% quartile age in both the group was 62 years (P = 0.06). There were 30 males, and 20 females. The median PCO score at 6, 12 and 24 months was significantly low in the rotation group (0.15, 0.13, 0.22) compared to the control group (0.22, 0.23, 0.25). There was no significant difference in PCO score between the two groups from 24-36 months. The median PCO score at 36 months was 0.2 in both the groups. At the end of three years, 4 eyes (8%) in the rotation group, and 10 eyes (20%) in the control group needed Nd:YAG capsulotomy (P = 0.04).ConclusionRotation of IOL in the capsular bag decreases PCO and Nd:YAG capsulotomy rate.
| S-EPMC6727723 | biostudies-literature
Project description:Cataract is the leading cause of visual impairment, and posterior capsular opacification (PCO) is the most common long-term complication of modern cataract surgery, which can cause severe visual impairment after surgery. The proliferation, migration, and epithelial-mesenchymal transition (EMT) of residual lens epithelial cells (LECs) stimulated by growth factors and cytokines, are the key pathological mechanisms involved in the development of PCO. This study demonstrated that non-steroidal anti-inflammatory drug (NSAID), bromfenac, was capable of effectively inhibiting cell migration, overexpression of EMT markers, such as fibronectin (FN), matrix metalloproteinase 2 (MMP2), α-smooth muscle actin (α-SMA), and transcription factor Snail, and extracellular signal-regulated kinase (ERK)/glycogen synthase kinase-3β (GSK-3β) signaling induced by transforming growth factor-β2 (TGF-β2) in vitro. The inhibitory effect of bromfenac on TGF-β2-induced EMT was also verified on a primary lens epithelial cell model using human anterior capsules. Furthermore, based on ultrasonic spray technology, we developed a drug-eluting intraocular lens (IOL) using poly (lactic-co-glycolic acid) (PLGA) with sustained bromfenac release ability for the prevention of PCO development. In the rabbit models of cataract surgery, bromfenac-eluting IOL exhibited remarkable PCO prevention and inflammation suppression effects with excellent biocompatibility. In conclusion, bromfenac can inhibit TGF-β2-induced cell migration and the EMT of LECs via ERK/GSK-3β/Snail signaling. The present study offers a novel approach for preventing PCO through PLGA-based drug sustained-release IOLs. Graphical abstract TGF-β2 promoted migration and EMT of lens epithelial cells (LECs) through activation of ERK/GSK-3β/Snail signaling, which could be suppressed by bromfenac. Novel bromfenac-based drug-eluting IOLs exhibited excellent PCO prevention in vivo.Image 1 Highlights • Bromfenac inhibited TGF-β2-induced migration and EMT of LECs through ERK/GSK-3β/Snail signaling.• Drug-eluting IOLs with sustained bromfenac release were developed based on ultrasonic spray technology.• Bromfenac-eluting IOLs exhibited remarkable PCO prevention and inflammation suppression effects in vivo.• Bromfenac-eluting IOLs hold great potential for clinical application of PCO prevention.
| S-EPMC8586266 | biostudies-literature
Project description:Posterior Capsular Opacification (PCO) is the capsule fibrosis developed on implanted IntraOcular Lens (IOL) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing Epithelial Mesenchymal Transition (EMT). Literature has shown that the incidence of PCO is multifactorial including the patient's age or disease, surgical technique, and IOL design and material. Reports comparing hydrophilic and hydrophobic acrylic IOLs have shown that the former has more severe PCO. On the other hand, we have previously demonstrated that the adhesion of LECs is favored on hydrophobic compared to hydrophilic materials. By combining these two facts and contemporary knowledge in PCO development via the EMT pathway, we propose a biomimetically inspired strategy to promote LEC adhesion without de-differentiation to reduce the risk of PCO development. By surface grafting of a cell adhesion molecule (RGD peptide) onto the conventional hydrophilic acrylic IOL material, the surface-functionalized IOL can be used to reconstitute a capsule-LEC-IOL sandwich structure, which has been considered to prevent PCO formation in literature. Our results show that the innovative biomaterial improves LEC adhesion, while also exhibiting similar optical (light transmittance, optical bench) and mechanical (haptic compression force, IOL injection force) properties compared to the starting material. In addition, compared to the hydrophobic IOL material, our bioactive biomaterial exhibits similar abilities in LEC adhesion, morphology maintenance, and EMT biomarker expression, which is the crucial pathway to induce PCO. The in vitro assays suggest that this biomaterial has the potential to reduce the risk factor of PCO development.
| S-EPMC4263720 | biostudies-literature
Project description:PurposeTo establish an optical section-assisted in vivo rabbit model for capsular bend and posterior capsule opacification (PCO) investigation.MethodsA total of 10 rabbits underwent phacoemulsification surgery and intraocular lens (IOL) implantation. On the basis of the relationship between the anterior capsule and IOL, the rabbits were divided into complete overlap and incomplete overlap groups, in which six and four rabbits were included, respectively. The capsular bend optical sections were assessed using ultra-long scan depth optical coherence tomography (UL-OCT), and posterior capsule opacification was evaluated with slit lamp on postoperative day 3, 7, 14, and 28. In addition, histopathological section was used to verify the accuracy of capsular bend type captured by OCT in three rabbits.ResultsBased on the special animal model, six capsular bend types were observed, namely, anterior (A), middle (M), posterior (P), detachment (D), funnel (Fun) and furcate adhesion (Fur). On day 3, capsular bend began to form. On 14 days, the capsular bends were comprised of A, M and D types, which were almost maintained until day 28. Histopathological section findings were consistent with optical sectioning results. In the incomplete and complete groups, the earliest PCO within the optical zone were on day 7 and 28, respectively. The incomplete group exhibited higher incidence and faster PCO on day 7 (p = 0.038) and 14 (p = 0.002).ConclusionsThis animal model not only mimics capsular bend evolution and PCO processes but also produces OCT optical section images equivalent to and more repeatable than histopathology, thereby providing a promising method for the further investigations of PCO.
| S-EPMC4739694 | biostudies-literature