Application of sustained delivery microsphere of cyclosporine A for preventing posterior capsular opacification in rabbits

AIM:To explore the inhibitory effect of a sustained cyclosporin A (CsA) delivery microsphere (CsA-MS) on posterior capsular opacification (PCO) in rabbit eyes after cataract extraction. ·METHODS:Twenty New Zealand white rabbits accepted cataract extraction plus intraocular lens implantation and their left eyes were intraoperatively injected CsA-MS prepared using polymer polylactioglycolic acid (PLGA) as a carrier and their right eyes were injected with empty MS. The changes in cornea, anterior chamber reaction, intraocular pressure, PCO and CsA concentration in aqueous humor were examined postoperatively and all the eyes were enucleated 3 months after surgery for histopathological and morphological examination with light microscopy and electron microscopy. · RESULTS:Conjunctival hyperemia, corneal edema, intraocular pressure and anterior chamber response of experimental and control eyes were similar, while PCO in CsA MS injected eyes was greatly improved compared with that in control eyes. Posterior capsules in CsA-MS injected eyes were smooth and lens epithelial cells (LEC) did not proliferate significantly (P 】0.05), while LEC in posterior capsule of control eyes had different degrees of proliferation and cortical regeneration. LEC in CsA-MS injected eyes were not functionally active and underwent apoptosis, whereas LEC in control eyes were functionally active (F-test, P =0.025). In addition, the cornealultrastructure showed no differences between CsA-MS and MS injected eyes. CONCLUSION:CsA-MS has high bioavailability in rabbit eyes and could inhibit postoperative PCO occurrence and development during the study period, suggesting that CsA-MS may be a promising, effective and safe administration route to prevent PCO in clinic.

Effect of four different intraocular lenses on posterior capsule opacification

AIM: To evaluate the impact of 4 different intraocular lenses(IOLs) on posterior capsule opacification(PCO) by comparing the neodymium: yttrium-aluminum-garnet(Nd:YAG) laser capsulotomy rates.METHODS: This retrospective study included 4970 eyes of 4013 cataract patients who underwent phacoemulsification and IOL implantation between January 2000 and January 2008 by the same surgeon at one clinic. Four different IOLs were assessed. The outcome parameter was the incidence of Nd:YAG laser posterior capsulotomies.· RESULTS: An Nd:YAG laser posterior capsulotomy was performed in 153(3.07%) of the 4970 eyes. The mean follow-up time was 84 mo for all of the IOL groups. The percentage of eyes developing PCO was significantly greater for the acrylic hydrophilic IOLs than for the hydrophobic IOLs, although eyes with acrylic hydrophilic IOLs did not require Nd:YAG laser capsulotomy as soon as eyes with acrylic hydrophobic IOLs. There was no difference between the long-term PCO rates when 1-and 3-piece acrylic hydrophobic IOLs were compared or when IOLs made of the same material but with different haptic angles were compared.· CONCLUSION: In this study, eyes with acrylic hydrophilic IOLs were more likely to develop PCO than those with acrylic hydrophobic IOLs. The lens design(1-piece versus 3-piece and varying haptic angles) did not affect the PCO rate.

Comparison of posterior capsule opacification at 360-degree square edge hydrophilic and sharp edge hydrophobic acrylic intraocular lens in diabetic patients

·AIM: To compare posterior capsule opacification(PCO)degree and visual functions after phacoemulsification in eyes implanted with 360-degree square edge hydrophilic acrylic intraocular lens(IOL)(570C C-flex, Rayner) and sharp edge hydrophobic acrylic IOL(Sensar AR40 e,AMO) in diabetic patients.· METHODS: Sixty diabetic patients underwent uneventful phacoemulsification and randomly implanted one of the two IOLs. The PCO value was measured by retroillumination photographs and Evaluation of Posterior Capsule Opacification(EPCO) 2000 image-analysis software at 1, 6, 12, and 24 mo after surgery. Visual acuity, and contrast sensitivity in photopic and mesopic conditions were also examined at each follow up time point. The incidence of eye that required Nd:YAG laser posterior capsulotomy were also compared.·RESULTS: There was not any statistically significant difference in PCO scores between Rayner C-flex 570 C group and Sensar AR40 e group at each follow up time point. Visual acuity, Nd:YAG capsulotomy incidence and contrast sensitivity also had no significant difference during the 24 mo follow-up.·CONCLUSION: For diabetic patients, Rayner 570 C Cflex and Sensar AR40 e IOLs are same effective for prevent PCO. The 360-degree square edge design maybe is a good alternative technique to improve PCO prevention.

Hydrophobic versus hydrophilic acrylic intraocular lens on posterior capsule opacification: a Meta-analysis

AIM: To conduct a Meta-analysis pooling randomized controlled trials(RCTs) to compare hydrophobic with hydrophilic acrylic intraocular lenses in terms of posterior capsule opacification(PCO) development.METHODS: Electronic databases including PubMed,Embase, and the Cochrane Library were queried from their starting till January 2020. RCTs investigating the impact of hydrophobic versus hydrophilic acrylic intraocular lenses on PCO were considered eligible in this study. The pooled effect estimates were calculated using the random-effects model.RESULTS: Thirteen RCTs comprising of 939 patients(1263 eyes) were covered in this study. Patients with hydrophobic acrylic intraocular lenses had a lower PCO score than those with a hydrophilic acrylic intraocular lenses [standard mean difference:-1.80;95% confidence interval(CI):-2.62 to-0.98;P<0.001]. Moreover, the frequency of neodymium-doped yttrium aluminum garnet(Nd:YAG)capsulotomy in patients with hydrophobic acrylic intraocular lenses was significantly lower than patients with hydrophilic acrylic intraocular lenses(relative risk: 0.38;95%CI: 0.20-0.71;P=0.003).CONCLUSION: These findings suggest that hydrophobic acrylic intraocular lenses are superior to hydrophilic acrylic intraocular lenses in patients after cataract surgery due to lower PCO score and reduced Nd:YAG capsulotomy. While similar studies are conducted by other researchers, the present study conducted subgroup analyses that show superior results with hydrophobic lenses in trials conducted in western countries.

“NIR-triggered ROS storage”photodynamic intraocular implant for high-efficient and safe posterior capsular opacification prevention

Posterior capsular opacification(PCO)is the leading cause of vision loss after cataract,mainly caused by the adhesion,proliferation and trans-differentiation of post-operative residual lens epithelial cells(LECs).Effective PCO prevention remains a huge challenge to ophthalmologists and researches for decades.Herein,we developed a“NIR-triggered ROS storage”intraocular implant(CTR-Py-Pp IX)based on capsular tension ring(CTR),which is concurrently linked with photosensitizer protophorphyrin IX(Pp IX)and energy storage2-pyridone derivative(Py),to guarantee instantaneous and sustainable ROS generation for LECs killing,aiming to achieve more efficient and safer photodynamic therapy(PDT)to effectively prevent PCO.The silylated Pp IX-Si and Py-Si were covalently conjugated to the plasma activated CTR surface to obtain CTR-Py-Pp IX.Results demonstrated that CTR-Py-Pp IX had dual functions of PDT and battery,in which Pp IX could generate ROS extracellularly under irradiation,with one part directly inhibiting LECs by lipid peroxidation(LPO)induction of cell membranes.Meanwhile,the excess ROS stored in Py could be continuously released to amplify LPO levels after the irradiation was removed.Ultimately,the proliferation of LECs in capsular bag was completely inhibited under mild irradiation conditions,achieving a sustainable and controlled PDT effect for effective PCO prevention with good biocompatibility.This NIR-triggered ROS storage intraocular implant would provide a more efficient and safer approach for long-term PCO prevention.

Etiology, pathogenesis, and management of acute intraocular lens opacification: a systematic review

Millions of cataract surgeries with intraocular lens(IOL) implantation are performed worldwide. Although cataract surgery brings many benefits to the patients, the risk of various complications is still a concern. One of the infrequent adverse events but potentially affecting on patients’ visual acuity and contrast sensitivity is losing the transparency of IOL. IOL opacification may lead to IOL removal or exchange, which is unpleasant to both the patient and the surgeon. Several reports of acute IOL clouding are available in the literature describing various etiologies of this phenomenon, however, the exact mechanism remained unclear in some cases. Herein, we aimed to review the causes and outcomes of intraoperative and early postoperative IOL opacification.

Staged lensectomy and vitrectomy in the management of stage 5C retinopathy of prematurity with corneal opacification:long-term follow up

·AIM:To verify the feasibility and safety of staged lensectomy and vitrectomy in stage 5 C retinopathy of prematurity(ROP)with corneal opacification.·METHODS:This was a retrospective,interventional,consecutive case series.Twenty-two eyes of 18 stage 5 C ROP patients with corneal opacification were included.Regular combined lensectomy and vitrectomy were not prescribed due to the invisible fundus.Staged lensectomy and posterior vitrectomy were performed.The anatomical and visual outcomes were reviewed at the final follow-up visit.·RESULTS:The mean gestational age of ROP patients was29.3±1.6 wk(range:27-32 wk),comprising 8 males and 10 females.The average birth weight was 1363.0±300.0 g.All the eyes had corneal opacity and flat or disappeared anterior chambers pre-operatively.Two eyes had complicated cataract and 7 eyes had retrolental fibroplasia.Six eyes had posterior pupillary synechiae or membranes.Seven(31.8%)eyes had vascularly active retinas.The average interval between two procedures was 6.8±4.6 mo(2.5-18.5 mo).After surgeries,all the patients had normal anterior chambers.Fourteen eyes had clear corneas.The intraocular pressure of 3 eyes with glaucoma was controlled by medication.Two eyes had ocular phthisis.The retina was reattached in 3 eyes and partially attached in 11 eyes.Visual acuity ranged from no light perception to hand motion.·CONCLUSION:Staged lensectomy and vitrectomy are procedures that can halt progression to further complications and preserve some useful eyesight in stage5 C ROP patients with corneal opacification.The earlier the lensectomy is performed,the better the prognosis is.

Experimental study on cyclosporine A drug delivery system in prevention of posterior capsule opacification after intraocular lens implantation in rabbits

Objective To study the effect of cyclosporine A drug delivery system (CsA-DDS) on the prevention of posterior capsule opacification (PCO) after experimental intraocular lens implantation in rabbit eyes. Methods Twenty healthy New Zealand white rabbits, whose left eyes and right eyes were used respectively as experiment eyes and controls, were subjected to extracapsular lens extraction and artificial lens implantation. During the operation, CsA-DDS with poly (lactideco-glycolide) as carriers or empty DDS was implanted in the capsular bag for the experimental eyes and controls respectively. After the operation, anterior chamber reaction, intraocular pressure (IOP) and CsA concentration were monitored and twelve weeks after the operation, the eyes were extracted for histopathological and morphological examinations. Results There were no differences between the two groups in conjunctival congestion, IOP change and anterior chamber reaction. PCO was less severe in the experimental eyes than in the controls. Light microscopy revealed that posterior capsular membrane in the experimental eyes was slick, with no obvious proliferation, whereas in the controls, there were lens epithelial cell proliferation and cortex regeneration of different degrees. Morphological examination with electron microscope showed that in the experimental eyes, lens epithelial cells did not function actively and apoptosis occurred, whereas in the controls, epithelial cells presented active function. No marked ultrastructural changes were found in either group. Conclusion Cs-DDS can inhibit PCO after intraocular lens implantation in rabbit eyes and does not have toxic effects on the surrounding ocular tissues. Therefore, it has a good potential for clinical use in prevention of PCO.

Anterior segment OCT application in quantifying posterior capsule opacification severity with varied intraocular lens designs

AIM:To evaluate the application of anterior segmentoptical coherence tomography(AS-OCT)in posterior capsule opacification(PCO)severity assessment and analyse the relationship between PCO severity and intraocular lens(IOL)characters.METHODS:PCO patients were prospectively recruited.Cross-sectional images of the anterior segment at horizontal and vertical meridians were acquired with AS-OCT.The area of the IOL-PC(posterior capsular)space and PCO severity(area,thickness,and density at 3 mm and 5 mm IOL optic regions)were measured.The relationship between PCO severity and visual acuity,comparisons of PCO severity and IOL-PC space using varied IOL designs were analysed.RESULTS:One hundred PCO eyes were enrolled.IOL-PC space,PCO thickness and area were positively correlated with axial length.In addition,PCO area and thickness were positively correlated with visual acuity when it was≤0.52 log MAR.The cut-off level of visual acuity should be 0.52 log MAR.With varied IOL designs,3-piece C haptic IOL showed a smaller PCO area and thickness than the 1-piece 3 haptic IOL and 1-piece 4 haptic IOL.PCO area and thickness values for an IOL with a diameter≤11.0 mm was greater than for an IOL with a diameter of 12.5 mm,and the differences were statistically significant.PCO area and thickness increased when IOL haptic angulation increased(from 0 to 12 degrees).CONCLUSION:In PCO eyes,cut-off level of visual acuity is 0.52 log MAR.With more severe PCO,visual acuity maybenot enough to describe the visual function impairment.PCO severity and IOL-PC space are significantly correlated with axial length and IOL design and material.

Fabrication of a 3D bioprinting model for posterior capsule opacification using GelMA and PLMA hydrogel-coated resin

Posterior capsule opacification(PCO)remains the predominant complication following cataract surgery,significantly impairing visual function restoration.In this study,we developed a PCO model that closely mimics the anatomical structure of the crystalline lens capsule post-surgery.The model incorporated a threaded structure for accurate positioning and observation,allowing for opening and closing.Utilizing 3D printing technology,a stable external support system was created using resin material consisting of a rigid,hollow base and cover.To replicate the lens capsule structure,a thin hydrogel coating was applied to the resin scaffold.The biocompatibility and impact on cellular functionality of various hydrogel compositions were assessed through an array of staining techniques,including calcein-AM/PI staining,rhodamine staining,BODIPY-C11 staining and EdU staining in conjunction with transwell assays.Additionally,the PCO model was utilized to investigate the effects of eight drugs with anti-inflammatory and anti-proliferative properties,including 5-aminoimidazole-4-carboxamide ribonucleotide(AICAR),THZ1,sorbinil,4-octyl itaconate(4-OI),xanthohumol,zebularine,rapamycin and caffeic acid phenethyl ester,on human lens epithelial cells(HLECs).Confocal microscopy facilitated comprehensive imaging of the PCO model.The results demonstrated that the GelMA 605%þPLMA 2%composite hydrogel exhibited superior biocompatibility and minimal lipid peroxidation levels among the tested hydrogels.Moreover,compared to using hydrogel as the material for 3D printing the entire model,applying surface hydrogel spin coating with parameters of 2000 rpm�2 on the resin-based 3D printed base yielded a more uniform cell distribution and reduced apoptosis.Furthermore,rapamycin,4-OI and AICAR demonstrated potent antiproliferative effects in the drug intervention study.Confocal microscopy imaging revealed a uniform distribution of HLECs along the anatomical structure of the crystalline lens capsule within the PCO model,showcasing robust cell viability and regular morphology.In conclusion,the PCO model provides a valuable experimental platform for studying PCO pathogenesis and exploring potential therapeutic interventions.

Non-viral gene coating modified IOL delivering PDGFR-αshRNA interferes with the fibrogenic process to prevent posterior capsular opacification

Posterior capsule opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and epithelial-mesenchymal transition(EMT)of residual lens epithelial cells in the capsule bag.Although the surface modification and drug loading of intraocular lens(IOLs)have been effective in preventing PCO to some extent,the intraocular safety of anti-proliferative drug application is still a major limitation in clinical application.In this study,we used non-viral gene delivery systems in combination with layer-by-layer(LBL)self-assembly technology,and the modified IOL could effectively prevent the development of PCO by interfering with the EMT process mediated by the platelet-derived growth factor receptor-α(PDGFR-α).Herein,the gene fragments were wrapped by electrostatic conjugation using polyethyleneimine-graft-poly(ethylene glycol)to form gene complexes.Gene complexes were characterized by dynamic light scattering,transmission electron microscopy(TEM)and agarose gel electrophoresis,and evaluated for storage and serum stability.The layer assembly behavior of the IOL surface,changes in optical properties and the release behavior of the gene complexes were characterized using quartz crystal microbalance,UV-vis,contact angle and TEM.In vitro experiments showed that the IOL coating has good bio-compatibility and can achieve the corresponding transfection effect,and the released gene complexes exhibited excellent cell internalization and lysosomal escape behaviors,as well as effective inhibition of PDGFR-αexpression and its mediated EMT process.The early PCO prevention effect and bio-compatibility evaluation of the modified IOL in vivo were evaluated by implantation into animal eyes.This study provides a new strategy for the development of surface modifications of small nucleic acid drugs and non-toxic EMT interference therapies for PCO.

Prophylaxis of posterior capsule opacification through autophagy activation with indomethacin-eluting intraocular lens

Posterior capsule opacification(PCO)is the most common long-term postoperative complication of cataract surgery,leading to secondary vision loss.Optimized intraocular lens(IOL)structure and appropriate pharmacological intervention,which provides physical barriers and biological inhibition,respectively,can block the migration,proliferation,and epithelial-mesenchymal transition(EMT)of lens epithelial cells(LECs)for PCO prophylaxis.Herein,a novel indomethacin-eluting IOL(INDOM-IOL)with an optimized sharper edge and a sustained drug release behavior was developed for PCO prevention.Indomethacin(INDOM),an ophthalmic non-steroidal anti-inflammatory drug(NSAID)used for postoperative ocular inflammation,was demonstrated to not only be able to suppress cell migration and down-regulate the expression of cyclooxygenase-2(COX-2)and EMT markers,including alpha-smooth muscle actin(α-SMA)and cyclin D1,but also promote the autophagy activation in LECs.Additionally,autophagy was also verified to be a potential therapeutic target for the down-regulation of EMT in LECs.The novel IOL,serving as a drug delivery platform,could carry an adjustable dose of hydrophobic indomethacin with sustained drug release ability for more than 28 days.In the rabbit PCO model,the indomethacin-eluting IOL showed excellent anti-inflammatory and anti-PCO effects.In summary,indomethacin is an effective pharmacological intervention in PCO prophylaxis,and the novel IOL we developed prevented PCO in vivo under its sustained indomethacin release property,which provided a promising approach for PCO prophylaxis in clinical application.

Late postoperative opacification of a new type hydrophilic acrylic intraocular lens

Background:To report the clinical consequences and laboratory characteristics of late postoperative opacification of a hydrophilic acrylic intraocular lens(US-860UV IOL)as well as the prognosis of IOL replacement.Methods:Forty medical records(42 eyes)of patients with US-860UV IOL opacification reporting decreased or lost vision who underwent IOL explantation between 2017 and 2019 were reviewed.Explanted IOLs were analyzed by slit-lamp examination,confocal microscopy,scanning electron microscopy(SEM)and energy-dispersive X-ray spectroscopy(EDS)at the Shandong Key Laboratory of Ophthalmology,Shandong Eye Institute,Shandong First Medical University,and Qingdao University of Science and Technology,Qingdao,China.Results:The mean age of the 40 patients was 74.837.57(63–92)years.The mean interval between cataract surgery and diagnosis of opacification was 32.388.76(17–48)months.Systemic diseases were found without statistical correlations,the most frequent being arterial hypertension,coronary heart disease,and diabetes mellitus.Visual acuity improved from 1.42±1.03 to 0.31±0.16(logMAR)after IOL replacement.SEM,EDS and alizarin red staining showed uniformly distributed,diffuse,milk-white opacification,with calcium and phosphorus deposits on the optic and haptic surfaces that could be dissolved in 1%HCl.Conclusions:Calcium and phosphorus deposition was the main cause of hydrophilic acrylic US-860UV IOL opacification.IOL replacement can safely and effectively improve the visual acuity of patients.

Consilience and unity in ocular anterior segment research

In his beautiful book,Consilience:The Unity of Knowledge,the eminent biologist Edward O Wilson,advocates the need for integration and reconciliation across the sciences.He defines consilience as“literally a‘jumping together’of knowledge with a linking of facts…to create a common groundwork of explanation”.It is the premise of this paper that as much as basic biomedical research is in need of data generation using the latest available techniques–unifying available knowledge is just as critical.This involves the necessity to resolve contradictory findings,reduce silos,and acknowledge complexity.We take the cornea and the lens as case studies of our premise.Specifically,in this perspective,we discuss the conflicting and fragmented information on protein aggregation,oxidative damage,and fibrosis.These are fields of study that are integrally tied to anterior segment research.Our goal is to highlight the vital need for Wilson’s consilience and unity of knowledge which in turn should lead to enhanced rigor and reproducibility,and most importantly,to greater understanding and not simply knowing.

Overexpression of TRPV1 activates autophagy in human lens epithelial cells under hyperosmotic stress through Ca^(2+)-dependent AMPK/mTOR pathway

●AIM:To explore whether autophagy functions as a cellular adaptation mechanism in lens epithelial cells(LECs)under hyperosmotic stress.●METHODS:LECs were treated with hyperosmotic stress at the concentration of 270,300,400,500,or 600 mOsm for 6,12,18,24h in vitro.Polymerase chain reaction(PCR)was employed for the mRNA expression of autophagyrelated genes,while Western blotting detected the targeted protein expression.The transfection of stub-RFP-sens-GFPLC3 autophagy-related double fluorescence lentivirus was conducted to detect the level of autophagy flux.Scanning electron microscopy was used to detect the existence of autolysosome.Short interfering RNA of autophagy-related gene(ATG)7,transient receptor potential vanilloid(TRPV)1 overexpression plasmid,related agonists and inhibitors were employed to their influence on autophagy related pathway.Flow cytometry was employed to test the apoptosis and intracellular Ca^(2+)level.Mitochondrial membrane potential was measured by JC-1 staining.The cell counting kit-8 assay was used to calculate the cellular viability.The wound healing assay was used to evaluate the wound closure rate.GraphPad 6.0 software was utilized to evaluate the data.●RESULTS:The hyperosmotic stress activated autophagy in a pressure-and time-dependent manner in LECs.Beclin 1 protein expression and conversion of LC3B II to LC3B I increased,whereas sequestosome-1(SQSTM1)protein expression decreased.Transient Ca^(2+)influx was stimulated caused by hyperosmotic stress,levels of mammalian target of rapamycin(mTOR)phosphorylation decreased,and the level of AMP-activated protein kinase(AMPK)phosphorylation increased in the early stage.Based on this evidence,autophagy activation through the Ca^(2+)-dependent AMPK/mTOR pathway might represent an adaptation process in LECs under hyperosmotic stress.Hyperosmotic stress decreased cellular viability and accelerated apoptosis in LECs and cellular migration decreased.Inhibition of autophagy by ATG7 knockdown had similar results.TRPV1 overexpression increased autophagy and might be crucial in the occurrence of autophagy promoted by hyperosmotic stress.●CONCLUSION:A combination of hyperosmotic stress and autophagy inhibition may be a promising approach to decrease the number of LECs in the capsular bag and pave the way for improving prevention of posterior capsular opacification and capsular fibrosis.

Drug-eluting intraocular lens with sustained bromfenac release for conquering posterior capsular opacification

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.

Augmented cellular uptake and homologous targeting of exosome-based drug loaded IOL for posterior capsular opacification prevention and biosafety improvement

Posterior capsular opacification(PCO),the most common complication after cataract surgery,is caused by the proliferation,migration and differentiation of residual lens epithelial cells(LECs)on the surface of the intraocular lens(IOL).Although drug-loaded IOLs have been successfully developed,the PCO prevention efficacy is still limited due to the lack of targeting and low bioavailability.In this investigation,an exosome-functionalized drug-loaded IOL was successfully developed for effective PCO prevention utilizing the homologous targeting and high biocompatibility of exosome.The exosomes derived from LECs were collected to load the anti-proliferative drug doxorubicin(Dox)through electroporation and then immobilized on the aminated IOLs surface through electrostatic interaction.In vitro experiments showed that significantly improved cellular uptake of Dox@Exos by LECs was achieved due to the targeting ability of exosome,compared with free Dox,thus resulting in superior anti-proliferation effect.In vivo animal investigations indicated that Dox@Exos-IOLs effectively inhibited the development of PCO and showed excellent intraocular biocompatibility.We believe that this work will provide a targeting strategy for PCO prevention through exosome-functionalized IOL.

An experimental study on the effects of curcumin on posterior capsule opacification in young rabbit eyes

Background Posterior capsule opacification （PCO） compromises vision development in infants after cataract surgery and lead to amblyopia. To observe the effects of curcumin on PCO in infant rabbits, curcumin was injected under the capaule and into the anterior chamber during phacoemulsification. Methods Seventy-five 1-month-old healthy New Zealand white rabbits were randomized into 3 groups, one eye of each rabbit was randomly selected to be operated. The operation involved continuous circular capsulorhexis, followed by hydrodissection with 0.6 ml each of balanced salt solution （BSS, group A）, hydroxypropyl-β-dodextrJn （HP-13-CD, 90μg/ml, group B） or CUR-HP-β-CD （123 μg/ml, group C）, respectively. After phacoemulsification, 0.4 ml of each drug solution was injected into the anterior chamber via an incision. The extent of corneal edema and the inflammatory response within the anterior chamber were considered as measures PCO and observed postoperatively. All eyes were examined 1 and 2 months postoperative by slit lamp microscopy and photography after pupil dilation. On the third day postoperative, 6 rabbits from each group were executed. Paraffin-embedded sections were stained with hematoxylin-eosin （HE） or terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL, indicative of apoptosis）. Stained sections were observed under light microscopy. Proliferation of lens epithelial cells （LECs） was observed microscopically on day 3, day 7, month 1 and month 2 after the operation with HE staining. Results The remission of cornea edema occurred earlier in group C than in groups A and B （P 〈0.05）; there were no significant differences between groups A and B. The remission of anterior chamber exudation in group C was earlier than those in groups A and B （P 〈0.05）. No significant difference in the times when PCO occurred, was observed among groups. Compared to groups A and B, the extent of PCO was less severe （P〈0.05）. Three days after the operation, LECs aggregated at the orbit. Meanwhile, minor apoptosis was observed in all groups. One month after the operation transparent, cortex and proliferating LECs were observed near the orbit in groups A and B. Two months postoperative, heavy cortex proliferation was observed in all groups： epithelial cells migrated and aggregated at the posterior capsule and rearranged under the anterior capsule in the control group. Proliferation was also observed in group C, but to a less severe extent than in the other two groups. Conclusion CUR-HP-β-CD exerts an inhibitory effect on PCO.

The influence of primary posterior continuous curvilinear capsulorhexis on posterior capsular opacification development in dogs

The posterior capsular opacification(PCO)is by far the most common complication following phacoemulsification.Posterior continuous curvilinear capsulorhexis(PCCC)is performed to prevent this complication in human beings.In PCCC,the central part of the posterior capsule is removed during cataract surgery to prevent equatorial lens cell migration onto the posterior capsule from reaching the visual axis.Up to now,there has no any report about PCCC in veterinary medicine.The aim of this study is to evaluate the efficacy of primary PCCC on the severity of posterior capsular opacification in dogs.

Astragalin attenuates diabetic cataracts via inhibiting aldose reductase activity in rats

AIM:To investigate the aldose reductase(AR)inhibition capacity of astragalin(AST)against streptozoticin-induced diabetic cataracts(DCs)in rats.METHODS:Ex vivo investigations were conducted by treating the lens of a goat placed for 72h in artificial aqueous humor(AAH)of pH 7.8 at room temperature with cataract-causing substance(55 mmol/L of galactose)and in vivo studies were performed on rats via induction with streptozotocin.AST was administered at different dose levels and scrutinize for DC activity.RESULTS:In diabetic rats,AST improved the body weight,blood insulin,and glucose as well as the levels of galactitol in a dose-dependent way,other biochemical parameters i.e.inflammatory mediators and cytokines,and also suppress AR activity.The level of the antioxidant parameters such as superoxide dismutase(SOD),catalase(CAT),and glutathione(GSH)activity were also altered on a diabetic lens after the administration of the AST.CONCLUSION:AST protects against lens opacification to avoid cataracts and polyols formation,indicating that it could be used as a potential therapeutic agent for diabetes.