[Application of optical coherence tomography in the assessment of the posterior lens capsule during anti-angiogenic therapy]. / Primenenie opticheskoi kogerentnoi tomografii v otsenke zadnei kapsuly khrustalika na fone provedeniya antiangiogennoi terapii.

Intravitreal injection (IVI) of anti-angiogenic drugs is one of the most common therapeutic procedures in ophthalmology. In recent years, a new non-contact study method has been developed - anterior segment optical coherence tomography (AS-OCT), which allows the formation of three-dimensional images of the lens and provides more detailed information about its structure and morphology. PURPOSE: This study uses optical coherence tomography method to analyze the risks of developing changes in the posterior lens capsule in patients after IVI of an anti-angiogenic drug. MATERIAL AND METHODS: The study involved 100 people (14 men and 86 women) with a natural lens and neovascular age-related macular degeneration (nAMD). The average age was 70.57±7.98 years. During the study (12 months), all patients underwent IVI of an anti-angiogenic drug aflibercept in the treat-and-extend (T&E) mode. All subjects were divided into 2 groups: with a total number of IVI less than 10 - group 1 (50 patients), and more than 10 IVI - group 2 (50 patients, of which 49 were included in the study). All patients underwent OCT using the Optopol REVO NX device (Poland) with the Anterior B-scan Wide protocol before inclusion in the study, as well as after 3, 6 and 12 months. RESULTS: It was found that the risk of developing a posterior lens capsule rupture, visualized using OCT, depends on the total number of IVI (correlation coefficient 0.473 p=0.001): the more IVI, the higher the probability that damage to the posterior capsule will occur after the next IVI, and after the 15th injection the risk of developing damage to the posterior capsule increases sharply. CONCLUSION: The astudy analyzed the risk factors for the development of posterior lens capsule damage that can be detected using OCT, and presented three risk groups for the development of rupture (or damage) of the posterior lens capsule depending on the number of intravitreal injections performed.

Posterior lens capsule rupture in non-diabetic canine cataracts: Pre-operative, intra-operative, and post-operative findings.

PURPOSE: To describe clinical features of non-diabetic canine cataracts with presumed pre-existing posterior capsule rupture (PLCR) and their surgical outcomes. METHODS: Clinical records of 497 non-diabetic canines that underwent elective cataract surgery were reviewed. Twelve canines met the inclusion criteria indicative of PLCR pre-dating surgery. RESULTS: The incidence of presumed pre-existing PLCR was 12/497 (2.4%). Cataracts included were unilateral in 10 out of 12 canines (83.3%) and bilateral in the remaining two (16.7%). Four eyes (28.6%) had clinically detectable pre-operative lens-induced uveitis. The mean age at cataract diagnosis for cases included was 6.6 years, and golden retrievers were the most common breed affected (28.6%). Phacoemulsification surgery was performed at a median time of 110 days (range 17-403 days) after presentation. Pre-existing PLCR was found intra-operatively as a large ellipse spanning the posterior capsule from equator to equator centrally in 12 eyes and peripherally in two eyes. The capsular defect in all eyes with PLCR incorporated a distinct "pseudo-capsule" preventing vitreal presentation and ruling out intraoperative surgeon rupture. Ten eyes (71.4%) received an intraocular lens implant (IOL), and 13 eyes (92.9%) maintained vision throughout a mean follow-up period of 12 months. CONCLUSION: Posterior lens capsule rupture of blunt trauma origin and associated cataract formation, as reported in humans, may also be an infrequent but distinct cause of some cases of non-diabetic canine cataracts. Medical management of phacolytic uveitis and delayed phacoemulsification surgery may be beneficial by allowing time for "pseudo-capsule" development, increasing the likelihood of IOL placement and improved visual outcomes.

[On studying the mechanisms and assessing the safety of Nd:YAG laser irradiation of the posterior lens capsule (experimental and clinical study)]. / K voprosu ob izuchenii mekhanizmov i otsenke bezopasnosti Nd:YAG-lazernoi destruktsii zadnei kapsuly khrustalika (eksperimental'no-klinicheskoe issledovanie).

YAG laser interventions are associated with the risk of complications, including corneal. PURPOSE: To study the mechanisms of laser destruction in exposing the posterior lens capsule (PLC) tissue to Nd:YAG laser irradiation, and to evaluate its side effects on the cornea. MATERIAL AND METHODS: The experiment involved 6 autopsy samples of human posterior lens capsule with different optical and mechanical properties, which were exposed to laser irradiation. We used the Nd:YAG ophthalmic laser LPULSA SYL-9000 Premio manufactured by «LightMed¼ (Taiwan/USA) and an experimental Nd:YAG laser system (1.064 µm). The following parameters were compared: the power of the incident radiation and radiation transmitted through the PLC, the mechanical stresses in the PLC tissue, the kinetic energy of the laser ablation products, and the pressure of gas bubbles during laser exposure in capsule samples of different densities. In the clinical part of the work, the negative effects of Nd:YAG laser on the cornea at different PLC densities were assessed using the endothelial microscope SP 3000P («Topcon¼, Japan). RESULTS: The experiment showed that in hard samples of PLC there are star-shaped point perforations with a diameter of 50±20 µm with partial rarefaction around the point defects. Damage to soft PLC samples in the form of large complete perforations was up to 200 µm in size. The temperature of laser irradiation necessary to achieve breakdown in soft PLC samples was 90 °C, in hard samples - 120 °C. The results of the experiment indicate that the final outcome - destruction of the PLC tissue - is safer to achieve not by increasing the energy, but by increasing the number of laser pulses. Clinical study results confirm a significant effect of the density of PLC on the values of laser energy and on the state of the cornea after laser intervention. CONCLUSION: The experimental data on the mechanisms of laser destruction of the lens capsule should contribute to the development of new and improvement of already known technologies aimed at reducing the risks associated with laser surgeries.

Inside-out and outside-in: Tips and tricks in posterior lenticonus.

Background: Posterior lenticonus is a congenital condition characterized by the thinning and bowing of posterior lenticular capsule. Cataract develops when normal intra-lenticular pressure bulges the posterior capsule at the circumscribed portion of inherent thin posterior lens capsule, leading to derangement of lamellar lens fibers. This condition poses a surgical challenge as the presentation varies from thin, bulging posterior capsule to large, pre-existing posterior capsular dehiscence. Purpose: This video highlights the tips for the surgical management of various scenarios of posterior lenticonus. Synopsis: In this video, tips for surgical management of various scenarios of posterior lenticonus are illustrated. Intraoperatively, ruptured posterior capsule is suspected by the presence of a fish-tail sign. The anterior capsulotomy is relatively easier in a flatter anterior lens capsule, owing to reduced intra-lenticular pressure. Hydro-dissection is avoided to prevent extension of pre-existing posterior capsular dehiscence or creation of rupture in a thinned-out capsule. The peripheral lens cortex aspiration is initiated first, followed by in each quadrant. In a presence of ruptured posterior capsule by vigilant inspection at this stage, the surgeon should change the direction of lens matter aspiration by aspirating the central lenticular matter first, followed by peripheral cortex like "inside-out". In absence of posterior capsule dehiscence, peripheral cortex is aspirated first, followed by central lens matter aspiration like "outside-in". Adequate anterior vitrectomy is performed until there are no vitreous tags. Highlights: In the presence of pre-existing posterior capsular defect, the lens matter is aspirated from the center (inside-out), whereas in the absence of capsular defect, the lens matter is aspirated from the periphery (outside-in). Online Video link: https://youtu.be/8G6BCbFwr8Q.

Short Term Visual and Refractive Outcome following Surgical Intervention forPosterior Capsule Opacification (PCO) in Children in a Tertiary Eye Hospital

BACKGROUND: PCO occurs commonly postoperatively followingcataract extraction in children, obscuring vision as did the initialcataract. It may require a second surgical procedure when it is dense.It is expected that this results in restoration of vision and it is importantto ascertain that this is the case as well as to examine any significantchanges in refraction thereafter.M ETHODS: A retrospective observational study extractingdemographic and clinical information from case notes of patients whohad membranectomy and/or capsule polishing between October 2017and September 2018.RESULTS: 57 eyes of 51 patients were enrolled. There was a 2:1male: female ratio. Mean age at cataract surgery was 6.33 3.59yearswhilst that for PCO surgery was 9.68 3.89years. Postoperativevisual acuity (by WHO definition) was good (between 6/6 and 6/18)in 33.3%, compared to 8.8% preoperatively. Whereas presenting visualacuity was poor (<6/60) in 61.4% preoperatively, this reduced to30% postoperatively. Visual outcome was influenced by age at cataractsurgery, age at PCO surgery, interval between cataract and PCO surgeryand type of cataract. Children >8 years of age at time of PCO surgeryhad a greater proportion of good post-operative best corrected visualacuity (BCVA) (52.6%), whilst 75% of children younger than 8yearsat time of surgery turned out with poor BCVA after surgery.Developmental cataracts proportionately had the best outcome ofvisual acuity. There was a range of refractive shift of +0.25D to ­5.25D with a mean myopic shift of ­1.51D following membranectomy. CONCLUSION: There was a good proportion of children withsignificant improvement in visual acuity on the short term,and a mildmyopic shift following membranectomy.

Role of Scheimpflug imaging for assessment of posterior lens capsule in pediatric traumatic cataract.

PURPOSE: To find the accuracy of Scheimpflug imaging for the evaluation of posterior lens capsule and to assess the incidence of pre-existing posterior capsular tear (PCT) in pediatric traumatic cataracts. METHODS: It was a prospective, non-randomized, and interventional study. Scheimpflug imaging was done preoperatively to detect pre-existing PCT in pediatric traumatic cataracts after blunt trauma. All patients underwent cataract extraction with intraocular lens implantation. Intraoperatively, the posterior capsule status was noted and compared with the preoperative Scheimpflug images. RESULTS: Forty-seven eyes of 47 children having traumatic cataracts following closed-globe injury were included. There were 32 males and 15 females with a mean age of 10.91 ± 2.75 years. The mean duration of performing the Scheimpflug imaging from injury was 41.7 ± 7.78 days. Preoperative Scheimpflug imaging showed intact posterior lens capsule in 36 eyes and PCT in 11 eyes. Intraoperative, 37 eyes had an intact posterior lens capsule and 10 eyes had PCT. The Scheimpflug imaging did not detect the PCT in three eyes (false-negative), and in four eyes, PCT was detected falsely on Scheimpflug imaging (false-positive). The sensitivity and specificity of the Scheimpflug imaging were 70 and 89.18%, respectively. The accuracy of the technique was 85.11%. CONCLUSION: Scheimpflug imaging is a useful modality for the detection of PCT preoperatively in cases with doubtful posterior lens capsule integrity.

The local wound environment is a key determinant of the outcome of TGFß signaling on the fibrotic response of CD44+ leader cells in an ex vivo post-cataract-surgery model.

The cytokine transforming growth factor beta (TGFß) has a role in regulating the normal and pathological response to wound healing, yet how it shifts from a pro-repair to a pro-fibrotic function within the wound environment is still unclear. Using a clinically relevant ex vivo post-cataract surgery model that mimics the lens fibrotic disease posterior capsule opacification (PCO), we investigated the influence of two distinct wound environments on shaping the TGFß-mediated injury response of CD44+ vimentin-rich leader cells. The substantial fibrotic response of this cell population occurred within a rigid wound environment under the control of endogenous TGFß. However, TGFß was dispensable for the role of leader cells in wound healing on the endogenous basement membrane wound environment, where repair occurs in the absence of a major fibrotic outcome. A difference between leader cell function in these distinct environments was their cell surface expression of the latent TGFß activator, αvß3 integrin. This receptor is exclusively found on this CD44+ cell population when they localize to the leading edge of the rigid wound environment. Providing exogenous TGFß to bypass any differences in the ability of the leader cells to sustain activation of TGFß in different environments revealed their inherent ability to induce pro-fibrotic reactions on the basement membrane wound environment. Furthermore, exposure of the leader cells in the rigid wound environment to TGFß led to an accelerated fibrotic response including the earlier appearance of pro-collagen + cells, alpha smooth muscle actin (αSMA)+ myofibroblasts, and increased fibrotic matrix production. Collectively, these findings show the influence of the local wound environment on the extent and severity of TGFß-induced fibrotic responses. These findings have important implications for understanding the development of the lens fibrotic disease PCO in response to cataract surgery wounding.

FILIP1L-mediated cell apoptosis, epithelial-mesenchymal transition and extracellular matrix synthesis aggravate posterior capsular opacification.

AIMS: The epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) synthesis and cell migration of residual lens cells constitute the canonical mechanisms of posterior capsular opacification (PCO). Recently, myofibroblast cell apoptosis is also observed in the rabbit PCO model. However, whether cell apoptosis is a key factor affecting PCO and regulates EMT/ECM synthesis/cell migration remains obscure. MAIN METHODS: Flow cytometry was utilized to assess cell cycle and apoptosis. EMT marker α-smooth muscle actin (α-SMA), ECM markers fibronectin (Fn), type 1 collagen (COL-1) and apoptosis-associated proteins in the presence or absence of EMT/ECM inhibitor (LY2109761), apoptosis inhibitor (ZVAD) or apoptosis activator (BTSA1) were detected by Western blotting. Downstream effector genes in apoptosis-induced lens epithelial cell lines (LECs) were analyzed by RNA-seq. Gene silencing and overexpression in LECs were performed to validate the role of effector genes. We measured cell migration capability using Wound healing and Transwell assays. KEY FINDINGS: We found that TGF-ß2 induced cell apoptosis. ZVAD inhibited α-SMA expression in the ex vivo capsule model and decreased the expression of both EMT and ECM markers in TGF-ß2-treated LECs. RNA-seq revealed that FILIP1L was significantly decreased in apoptosis-activated cells. We further validated that the knockdown of FILIP1L could enhance EMT and ECM synthesis and promote cell migration and that FILIP1L overexpression could reverse these effects. Apoptosis might contribute to TGF-ß2-induced EMT and ECM synthesis during PCO, and these contributions are mediated by FILIP1L. SIGNIFICANCE: Our findings uncover the role of apoptosis in PCO development and provide new drug targets.

Comperative analysis of accuracy between low-frequency ultrasound biomicroscopy and 14-MHz ultrasonography with tissue harmonic imaging for the evaluation of the posterior lens capsule in traumatic cataracts.

BACKGROUND: To compare the accuracy of low-frequency ultrasound biomicroscopy (LFUBM) and 14-MHz ultrasonography with tissue harmonic imaging (14-MHz + THI) in the assessment of posterior capsule (PC) integrity in patients with traumatic cataracts (TCs). METHODS: From January 2019 to October 2020, 51 patients (51 eyes) with TCs who were scheduled for cataract extraction and for whom the PC of the lens could not be observed by the slit lamp visited Tianjin Eye Hospital, including 47 patients (47 eyes) with a penetrating injury of the eyeball and 4 patients (4 eyes) with a blunt injury of the eyeball. All eyes underwent LFUBM and 14-MHz + THI examinations before cataract extraction to determine the integrity of the PC. The integrity of the PC observed in surgery was the actual findings, and the consistency between the 2 methods was assessed in terms of the preoperative examination and intraoperative findings. Fisher's exact test was used for consistency analysis, and P < 0.05 was considered statistically significant. RESULTS: Thirty-two eyes with ruptured PCs and 19 eyes with intact PCs were actual findings in surgery. Thirty eyes with ruptured PCs and 21 eyes with intact PCs were examined by LFUBM. Thirty-two eyes with ruptured PCs and 19 eyes with intact PCs were examined by 14-MHz + THI. There were no significant differences between the 2 methods and the intraoperative findings (P = 0.293 LFUBM, P = 0.623 14-MHz + THI). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of LFUBM and 14-MHz + THI were 91 and 94%, 95 and 89%, 97 and 94%, 86 and 89% and 92 and 92%, respectively. CONCLUSIONS: Both LFUBM and 14-MHz + THI were proved to have high levels sensitivity and specificity in diagnosing the status of the PC in TC and they can be used as accurate diagnostic tool in these cases.

Metformin attenuates the epithelial-mesenchymal transition of lens epithelial cells through the AMPK/TGF-ß/Smad2/3 signalling pathway.

Posterior capsule opacification (PCO) is a common ocular fibrosis disease related to the epithelial-mesenchymal transition (EMT) of human lens epithelial cells (HLECs). However, safe and effective drugs that prevent or treat PCO are lacking. Metformin (Mtf) has been used to treat fibrosis-related diseases affecting many organs and tissues, but its effect on ocular fibrosis-related diseases is unclear. We investigated whether Mtf can inhibit EMT and fibrosis in HLECs to prevent and treat PCO and elucidated the potential molecular mechanism. Here, we established an HLEC model of TGF-ß-induced EMT and found that 400 µM Mtf inhibited vertical and lateral migration and EMT-related gene and protein expression in HLECs. Smad2/3 are downstream molecules of TGF-ß that enter the nucleus to regulate EMT-related gene expression during the occurrence and development of PCO. We revealed that Mtf suppressed TGF-ß-induced Smad2/3 phosphorylation and nuclear translocation. Mtf induces AMP-activated protein kinase (AMPK) phosphorylation. In this study, we found that Mtf induced the activation of AMPK phosphorylation in HLECs. To further explore the mechanism of Mtf, we pretreated HLECs with Compound C (an AMPK inhibitor) to repeat the above experiments and found that Compound C abolished the inhibitory effect of Mtf on HLEC EMT and the TGF-ß/Smad2/3 signalling pathway. Thus, Mtf targets AMPK phosphorylation to inhibit the TGF-ß/Smad2/3 signalling pathway and prevent HLEC EMT. Notably, we first illustrated the AMPK/TGF-ß/Smad2/3 signalling pathway in HLECs, which may provide a new therapeutic strategy for PCO.

Effect of time and temperature-dependent changes of IOL material properties on IOL: Lens capsule interactions.

Posterior Capsule Opacification (PCO) is the most common complication associated with Intraocular Lens (IOL) implantation. Based on the assumption that the interactions between an IOL and the lens capsule (LC) may influence the extent of PCO formation, a new in vitro model was developed to quantify the adhesion force of an IOL to simulated LC using a custom-designed micro-force tester. Using this system, we examined the influence of temperature (room temperature vs. body temperature) and incubation time (0 vs. 24 h) on the adhesion force between IOLs and LCs. The results show that, in line with clinical observations of PCO incidence, the adhesion force increased at body temperature and with increase in incubation time in the following order, Acrylic foldable IOLs > Silicone IOLs > PMMA IOLs. By examining the changes of surface properties as a function of temperature and incubation time, we found that acrylic foldable IOLs showed the largest increase in their hydrophilicity and reported the lowest surface roughness in comparison to other IOL groups. Coincidentally, using a newly established macromolecular dye imaging system to simulate cell migration between IOLs and LC, we observed that the amount of macromolecular dye infiltration between IOLs and LCs was in the following order: PMMA IOLs > Silicone IOLs > Acrylic foldable IOLs. These results support a new potential mechanism that body temperature, incubation time, surface hydrophilicity and smoothness of IOLs greatly contribute to their tight binding to LCs and such tight binding may lead to reduced IOL: LC space, cell infiltration, and thus PCO formation.

The Protective Effect of Metformin Use on Early Nd:YAG Laser Capsulotomy.

Purpose: To determine the effect of metformin on early Nd:YAG laser treatment for posterior capsule opacification (PCO) and to explore a molecular mechanism to explain a possible protective effect of metformin against PCO. Methods: We conducted: 1) a retrospective cohort study of patient eyes undergoing phacoemulsification at our institution; and 2) laboratory investigation of the effect of metformin on the behavior of lens epithelial cells in the context of an animal model for PCO. Population-averaged Cox proportional hazards modeling was used to estimate risk for time to Nd:YAG. For laboratory studies, expression of markers for epithelial-to-mesenchymal transition (EMT) implicated in PCO pathogenesis was measured in tissue culture and following extracapsular lens extraction in a mouse model. Results: The rate of Nd:YAG laser capsulotomy was 13.1% among the 9798 eyes. Both metformin use and diabetes were protective factors for Nd:YAG laser capsulotomy in univariate analysis. However, in multivariable analysis with nondiabetics as the reference group, only metformin use among diabetics was significantly protective of Nd:YAG (hazard ratio: 0.68, 95% CI: 0.54-0.85, P = 0.0008), while eyes of patients with diabetes without metformin use did not significantly differ (P = 0.5026). Treatment of lens epithelial cells with metformin reduced the level of the EMT markers ⍺-SMA and pERK induced by TGF-ß2. Similarly, metformin treatment reduced ⍺-SMA expression in lens epithelial cells following extracapsular lens extraction in a mouse model. Conclusions: The protective effect of metformin against early Nd:YAG may relate to its ability to downregulate EMT in residual lens epithelial cells that otherwise trend toward myofibroblast development and PCO.

Inspection of the lens thickness with preoperative biometric measurements prevents an erroneous interpretation of posterior capsule during FLACS.

Optical opacity reduces quality of biometry images, making it potentially difficult to find the correct location for irradiation during femtosecond laser-assisted cataract surgery (FLACS). After experiencing a case of posterior capsule (PC) rupture because of optical opacity, we started lens thickness (LT) inspection, which indicates comparison of between intra- and pre-operatively measured LT. We retrospectively investigated the effectiveness of the LT inspection. One observer reviewed all FLACS treatment summaries for 3 years by CATALYS in the Jikei University Hospital, Tokyo. Based on the lines defining the PC on intraoperative OCT images, all cases were classified into three groups: undescribed, appropriate and inappropriate PC. Among the 1070 cases, 1047 cases had appropriate PC. In 19 cases, the PC line was undescribed because of dense cataract. Among 474 cases with no inspection, 4 cases had an inappropriate PC. Whereas, in 596 cases with the LT inspection, there was no case of an inappropriate PC. LT inspection significantly reduced the cases with inappropriate PC. The safety margins normally work to prevent severe complications. However, rare outlier cases had a high risk of severe complications. We propose LT inspection could be the most practical and convenient way for safety surgery.

Case Report: Role of Anterior Segment Optical Coherence Tomography in Late-onset Capsular Block Syndrome.

SIGNIFICANCE: We report the use of anterior segment optical coherence tomography (AS-OCT) as a valuable tool for capsular block syndrome diagnosis and follow-up. PURPOSE: The purposes of this study are to report a case of late-onset capsular block syndrome or lacteocrumenasia and to describe differential diagnosis with other more common phacoemulsification complications such as intraocular lens (IOL) or posterior capsule opacification. CASE REPORT: We report the case of a 56-year-old man with a clinical history of cataract surgery in his left eye. Five years after cataract surgery, he complained of blurred vision and was referred for IOL removal to our hospital. After careful slit-lamp examination, we found that the lens was clear, and opacity belonged to the accumulation of a whitish material in the capsular bag behind the lens. AS-OCT gave the definite diagnosis of capsular block syndrome. Intraocular lens removal had been wrongly indicated, and we treated our patient by YAG laser posterior capsulotomy. AS-OCT confirmed the absence of a further accumulated material, so no other interventions were needed. After treatment, best-corrected visual acuity improved from 0.48 to 0.1 logMAR. CONCLUSIONS: Capsular block syndrome is a rare late-onset complication of cataract surgery causing a deep visual acuity decay. A precise slit-lamp examination and AS-OCT, together, avoid misdiagnosis and unnecessary surgical treatment, which may be needed in case of IOL opacity or fibrotic-like lacteocrumenasia. AS-OCT also helps in determining the treatment outcome. Immediate best-corrected visual acuity improvement is reached after a successful intervention.

Exosome-transmitted circ-CARD6 facilitates posterior capsule opacification development by miR-31/FGF7 axis.

BACKGROUND: Posterior capsular opacification (PCO) is the major vision-disrupting complication arising after cataract surgery. Circular RNAs (circRNAs) are biological active RNAs which were involved in various physiological functions. So far, the role of circRNA caspase recruitment domain family member 6 (circ-CARD6) in PCO is still unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression of circ-CARD6, microRNA 31 (miR-31) and fibroblast growth factor 7 (FGF7) message RNA (mRNA). Western blot was used to analyze the protein expression. Transmission electron microscopy (TEM) was employed to capture the exosome image. The proliferation and metastasis were analyzed by cell counting kit-8 (CCK8), transwell and wound healing assays. The potential binding sequences between miR-31 and circ-CARD6 or FGF7 were respectively predicted by Circinteractome and Targetscan online tool, and verified by dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays. RESULTS: Exosome-transmitted circ-CARD6 was highly expressed in PCO tissues and TGF-ß2-treated SRA01/04 cells. Circ-CARD6 deletion repressed the proliferation, metastasis, EMT process and MAPK pathway, which was reversed by anti-miR-31 in TGF-ß2-treated SRA01/04 cells. Meanwhile, circ-CARD6 sponged miR-31 which directly targeted FGF7 in TGF-ß2-treated SRA01/04 cells. FGF7 overexpression allayed miR-31 overexpression-induced suppression in proliferation, metastasis, EMT process and MAPK pathway. Besides, circ-CARD6 regulated FGF7 expression by sponging miR-31. CONCLUSION: Circ-CARD6 promoted PCO development via miR-31/FGF7 axis. This finding might contribute to the development of the targeted therapy for PCO.

Assessment of intraocular lens/capsular bag biomechanical interactions following cataract surgery in a human in vitro graded culture capsular bag model.

Intraocular lenses (IOLs) are implanted during cataract surgery. For optimum results, stable positioning of the IOL in the capsular bag is important. Wound-healing events following cataract surgery lead to modification of the capsular bag and secondary visual loss due to posterior capsule opacification. At present, it is unclear how these biological events can affect stability of the IOL within the capsular bag. In the present study, a human in vitro graded culture capsular bag model was the experimental system. Capsulorhexis and lens extraction performed on human donor eyes generated suspended capsular bags (5 match-paired experiments). Preparations were secured by pinning the ciliary body to a silicone ring and maintained in 6 mL of medium for 84 days using a graded culture system: days 1-3, 5% human serum and 10 ng/mL transforming growth factor ß (TGFß2); days 4-7, 2% human serum and 1 ng/mL TGFß2; days 8-14, 1% human serum and 0.1 ng/mL TGFß2; days 15-84, serum-free Eagle's minimum essential medium (EMEM). A CT LUCIA 611PY IOL was implanted in all preparations. Quantitative measures were determined from whole bag images captured weekly. Images were registered using FIJI and analysed in ImageJ to determine capsular bag area; distortion; angle of contact; haptic stability; capsulorhexis area; and a fusion footprint associated with connection between the anterior and posterior capsules. Cell coverage and light scatter were quantified at end-point. The transdifferentiation marker, α-SMA was assessed by immunocytochemistry. Immediately following surgery, distortion of the capsular bag was evident, such that a long axis is generated between haptics relative to the non-haptic regions (short axis). The angle of contact between the haptics and the peripheral bag appeared inversely correlated to capsular bag area. Growth on the peripheral posterior capsule was observed 1 week after surgery and beneath the IOL within 1 month. As coverage of the posterior capsule progressed this was associated with matrix contraction/wrinkles of both the central posterior capsule and peripheral capsular bag. Cells on the central posterior capsule expressed αSMA. Fusion footprints formed in non-haptic regions of the peripheral bag and progressively increased over the culture period. Within and at the edge of the fusion footprint, refractive structures resembling lens fibre cells and Elschnig's pearls were observed. Cell attachment to the IOL was limited. An impression in the posterior capsule associated with the CT LUCIA 611PY optic edge was evident; cell density was much greater peripheral to this indent. Wound-healing events following surgery reduced capsular bag area. This was associated with the long/short axis ratio and angle of contact increasing with time. In summary, we have developed a human capsular bag model that exhibits features of fibrotic and regenerative PCO. The model permits biomechanical information to be obtained that enables better understanding of IOL characteristics in a clinically relevant biological system. Throughout culture the CT LUCIA 611PY appeared stable in its position and capsular bag modifications did not change this. We propose that the CT LUCIA 611PY optic edge shows an enhanced barrier function, which is likely to provide better PCO management in patients.

An in vitro system to investigate IOL: Lens capsule interaction.

Posterior capsule opacification (PCO) is the most common complication associated with intraocular lens (IOL) implantation. Unfortunately, current in vitro models cannot be used to assess the potential of PCO due to their failure to simulate the posterior curvature of the lens capsule (LC) and IOL, a factor known to affect PCO pathogenesis in clinic. To overcome such a challenge, a new system to study IOL: LC interaction and potentially predict PCO was developed in this effort. It is believed that the interactions between an IOL and the lens capsule may influence the extent of PCO formation. Specifically, strong adhesion force between an IOL and the LC may impede lens epithelial cell migration and proliferation and thus reduce PCO formation. To assess the adhesion force between an IOL and LC, a new in vitro model was established with simulated LC and a custom-designed micro-force tester. A method to fabricate simulated LCs was developed by imprinting IOLs onto molten gelatin to create simulated three dimensional (3D) LCs with curvature resembling the bag-like structure that collapses on the IOL post implantation. By pushing the LC mold vertically downward, while measuring the change in position of the bending bar with respect to its start position, the adhesion force between the IOLs and LCs was measured. An in vitro system that can measure the adhesion force reproducibly between an IOL and LC with a resolution of ~1 µN was established in this study. During system optimization, the 10% high molecular weight gelatin produced the best LC with the highest IOL: LC adhesion force with all test lenses that were fabricated from acrylic foldable, polymethylmethacrylate (PMMA) and silicone materials. Test IOLs exerted different adhesion force with the 3D simulated LCs in the following sequence: acrylic foldable IOL > silicone IOL > PMMA IOL. These results are in good agreement with the clinical observations associated with PCO performance of IOLs made of the same materials. This novel in vitro system can provide valuable insight on the IOL: LC interplay and its relationship to clinical PCO outcomes.