Immunoregulatory Properties of Immune Cells that Associate with the Lens Capsule Surface during Acute and Resolution Phases of Experimental Autoimmune Uveitis.

Inflammation in the eye is tightly regulated to prevent vision impairment and irreversible blindness. Emerging evidence shows that immune cells are specifically recruited to the lens capsule in response to autoimmune uveitis, yet the potential that they have a role in regulating this inflammatory disease remained unexplored. Here, an immunolocalization approach combined with high-resolution confocal microscopy was used to investigate whether the immune cells that become stably associated with the lens capsule in the eyes of C57BL/6J mice with experimental autoimmune uveitis (EAU) have an immunoregulatory phenotype. These studies revealed that during the acute phase of uveitis, at day 18 after disease induction, the immune cells specifically recruited to the lens capsule, such as regulatory T cells [forkhead box P3 (FoxP3)+CD4+] and M2 macrophages (CD68+ arginase 1+IL-10+), included those with putative anti-inflammatory, proresolution roles. The frequency of these lens capsule-associated immunomodulatory phenotypes increased at day 35 after induction, during the resolution phase of EAU inflammation. At this later stage of resolution, most of the macrophages expressed CD206, a mannose receptor responsible for removing inflammatory molecules, in addition to arginase 1 and IL-10. These results suggest a previously unknown role for the lens as a site for recruitment of immune cells whose role is to suppress inflammation, promote resolution, and maintain remission of EAU.

Transient anterior subcapsular vacuolar lens opacities after Tanito microhook trabeculotomy: report of six cases.

OBJECTIVE: To present six cases exhibiting transient anterior subcapsular vacuolar lens opacities following early postoperative Tanito microhook trabeculotomy (TMH) performed by the same surgeon. METHODS: Six patients who underwent lens-sparing TMH at Meizankai Shimizu Eye Clinic from November 2021 to May 2023, and developed anterior subcapsular vacuolar lens opacities postoperatively were reviewed. Detailed records of surgeries, follow-up findings were collected and reported. RESULTS: In all six cases, anterior vacuolar subcapsular lens opacities were observed on the day after surgery, gradually decreasing without affecting visual acuity or contrast sensitivity. In all cases, without any specific interventions, the opacities disappeared by 21 months postoperatively. CONCLUSION: Anterior subcapsular cataracts, characterized by a vacuolar appearance and transient existence, should be recognized as an early complication of ab interno glaucoma surgery, possibly linked to use of distributed ophthalmic viscosurgical devices and excessive anterior chamber irrigation leading to traumatic cataracts on the lens surface.

A potential role for inflammatory cytokines in a rare late-onset capsular block syndrome: a case report.

BACKGROUND: Late-onset capsule block syndrome (CBS) is a rare complication of cataract phacoemulsification and the implantation of a posterior chamber intraocular lens (PCIOL), which manifests six months to years after surgery. The hallmark of CBS is the formation of an opaque liquid substance between the implanted intraocular lens (IOL) and the posterior capsule. However, its pathogenesis remains unclear. CASE PRESENTATION: A 64-year-old female patient with chronic angle-closure glaucoma (axis length < 21 mm) underwent trabeculectomy surgery combined with phacoemulsification and PCIOL. After a 4-year follow-up, a decline in visual acuity occurred in her right eye due to the location of opaque fluid in the visual axis and distension of the capsular bag. The initial course of action was to release the trapped fluid. Neodymium: yttrium-aluminum-garnet (Nd: YAG) laser capsulotomy could not be employed due to her non-dilating pupil and high extension of the posterior capsule. Subsequently, anterior capsule peeling and anterior segment vitrectomy surgery were performed. The depth of the anterior chamber (ACD), the distance between the face of the retro-IOL and the posterior capsule, the best-corrected visual acuity (BCVA), and the visual quality (VQ) were measured both before and after surgery. Inflammatory cytokine levels in the opaque substances (OS) trapped between the PCIOL and the posterior capsule were assessed using a flow cytometer and compared to normal statistical data in aqueous humor. After surgery, the patient experienced a significant improvement in BCVA and VQ. The distance between the face of the retro-IOL and the posterior capsule was on the verge of disappearing. However, ACD did not differ between pre- and post-operatively. Interleukin-8 (IL-8) and basic fibroblast growth factor (BFGF) concentrations were higher in the OS than in aqueous humor, especially in the former. However, the concentration of vascular cell adhesion molecule (VCAM) in the OS was lower than in aqueous humor. CONCLUSIONS: Anterior segment vitrectomy surgery proved to be a successful treatment for late-onset CBS, presenting a challenging case. In the human lens, inflammatory cytokines originating from the opaque substances may contribute to abnormal metabolism in the sealed area, a consequence of late-onset CBS.

Association of CUL4B with the pathogenesis of age-related cataract.

PURPOSE: Age-related cataract (ARC) is the most common cause of visual impairment and blindness in older adults. However, the role of CUL4B in the ARC remains unclear. Therefore, we investigated CUL4B expression and its effects on apoptosis. MATERIALS AND METHODS: CUL4B expression levels were detected by a quantitative real-time polymerase chain reaction from the anterior lens capsules of patients with ARC and HLE-B3 cells treated with different concentrations of H2O2. CUL4B expression was silenced by siRNA transfection to evaluate apoptosis. CUL4B and apoptotic proteins B cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), caspase-3, cleaved caspase-3, Bax, Bak, and Bid were assessed using western blot analysis. Apoptosis was monitored using the TUNEL assay. RESULTS: CUL4B expression was downregulated in the anterior lens capsules (P < 0.0001) and H2O2-treated HLE-B3 cells (P = 0.0405). CUL4B protein levels were significantly lower in 100 µmol/L (P = 0.0012) and 200 µmol/L (P = 0.0041) H2O2-treated HLE-B3 cells than in the untreated cells. CUL4B expression was significantly knocked down at the mRNA (P = 0.0043) and protein levels (P = 0.0002) in HLE-B3 cells. Bcl-2 (P = 0.0199), Mcl-1 (P = 0.0042), and caspase-3 (P = 0.0142) were significantly downregulated, whereas cleaved caspase-3 (P = 0.0089) and Bak (P = 0.009) were significantly upregulated in the knockdown group. The TUNEL assay showed a greater induction of apoptosis. CONCLUSIONS: CUL4B downregulation promotes the apoptosis of lens epithelial cells. Our study may help in understanding the role of CUL4B in ARC pathogenesis.

Analysis of the capsular bend in posterior capsular opacification using anterior segment optical coherence tomography.

PURPOSE: To investigate the link between the capsular bend and the morphological types and characteristics of posterior capsular opacification (PCO) using anterior segment optical coherence tomography. METHODS: Thirty eyes with PCO were examined, and three types of PCO were identified: pearl, fibrosis, and mixed. We assessed anterior capsular overlap, intraocular lens-capsule adhesion, and capsular bending. In addition to measuring the intraocular lens-posterior capsule distance and capsule bending angle (CBA), the PCO parameters (area, density, and score at 6-, 5-, and 3-mm intraocular lens optic regions) were recorded. The associations between capsular bend and PCO type and characteristics were investigated. A control group of 12 eyes without PCO was used to compare the study variables. RESULTS: With p values greater than 0.001, there was a statistically significant difference in the mean PCO area and score at the 6-, 5-, and 3-mm optic zones in different PCO types, with the pearl type having the highest value, followed by the mixed type, and finally the fibrosis type. The PCO group had a significantly higher mean CBA than the control group (P = 0.001). CBA was positively related to intraocular lens-posterior capsule distance, PCO area, and PCO score at the 6-, 5-, and 3-mm zones (P = 0.001). The receiver operating characteristic curve's cut-off point for CBA was 96.85° when comparing PCO cases to controls. Partial overlap and incomplete adhesion were statistically more common in the PCO eyes than in the control (P = 0.001, 0.003, respectively). CONCLUSION: PCO types and CBA have a strong relationship with PCO score and intraocular lens-posterior capsule space. In PCO's eyes, CBA has a cut-off value of 96.85°.

Postoperative Endophthalmitis in Immediate Sequential Bilateral Cataract Surgery: A Nationwide Registry Study.

PURPOSE: To report the incidence of postoperative endophthalmitis (PE) after immediate sequential bilateral cataract surgery (ISBCS) in Sweden. DESIGN: Retrospective cohort registry study. PARTICIPANTS: Patient data from 1 457 172 cataract extractions, including 1 364 934 unilateral surgeries and 92 238 ISBCSs. METHODS: Endophthalmitis cases reported to the Swedish National Cataract Register (NCR) during a 16-year period (2002-2017) were analyzed in comparison to all control cases with regard to patient characteristics, surgical technique, and capsule complication. MAIN OUTCOME MEASURE: Incidence and determinants for PE in ISBCS compared with unilateral surgeries. RESULTS: A total of 422 cases of PE were identified in 1 457 172 cataract extractions, yielding an overall incidence of 0.029% (95% confidence interval [CI], 0.0262-0.0317). For unilateral procedures, the rate was 0.0299% (95% CI, 0.0270-0.0328) or 408 cases in 1 364 934 operations, whereas that for ISBCS was 0.0152% (95% CI, 0.0072-0.0231) or 14 incidents in 92 238 operations (P = 0.01). In a logistic regression model including all cataract procedures, nonuse of intracameral (IC) antibiotics (ABs), capsule complication, age 85 years or more, male gender, and ocular comorbidity were found to be independent risk factors for PE. All these parameters were less frequent in ISBCS. Notwithstanding, in the same multivariate analysis, ISBCS in itself was associated with a significantly lower risk for PE. At follow-up, 5 of the 14 PE cases in the ISBCS cohort had a visual acuity (VA) of 20/200 or worse. Of these, one 93-year-old ISBCS patient developed bilateral infection. CONCLUSIONS: After ISBCS in Sweden, PE occurred once in 6600 surgeries. The risk of sustaining a final VA of 20/200 or less was 1 incident in 18 000 operated eyes. When counseling potential ISBCS patients about the risk of PE, it seems reasonable to state that the reported risk in the literature is lower than that with unilateral surgery but not negligible. Precautions remain necessary.

OCULAR MANIFESTATIONS OF ASP38ALA AND THR59LYS FAMILIAL TRANSTHYRETIN AMYLOIDOSIS.

PURPOSE: To describe the ophthalmic manifestations of familial transthyretin amyloidosis (FTA) mutations, including Asp38Ala and Thr59Lys, which have not been previously reported to have ocular involvement. METHODS: This is an observational case series of prospectively collected data of 16 patients with FTA who were taking tafamidis for mild peripheral neuropathy and underwent a comprehensive ophthalmic examination at a single tertiary center, between January 2013 and March 2020. The ocular involvement of each FTA mutation type and the specific manifestations were the main outcome measures. RESULTS: Six of 16 patients with FTA manifested ocular involvement. Ocular involvement was noted in two of three patients with Glu89Lys mutations having retinal deposits, retinal hemorrhages, and corneal opacity. Three of nine patients with Asp38Ala mutations and one of two patients with Thr59Lys mutations showed ocular involvement that had not been previously described. The ophthalmic findings included glaucoma, anterior lens capsule opacity, vitreous opacity, and retinal deposits. The decrease in vascular flow due to perivascular cuffing of the amyloid deposits was detected by optical coherence tomography angiography. CONCLUSION: The current study newly described that two transthyretin mutation types of FTA, Asp38Ala and Thr59Lys, may manifest with ocular findings such as anterior lens capsule opacity and retinal deposits.

Proteomic analysis of aqueous humor from cataract patients with retinitis pigmentosa.

A postcataract surgery complication in patients with retinitis pigmentosa (RP) is lens capsular contraction. To identify potential proteins contributing to this phenomenon, high-performance liquid chromatography/mass spectrometry-based proteomic analysis was conducted with aqueous humor samples collected from 11 patients who underwent cataract surgeries, with four patients diagnosed as RP and cataract (RP group) and the other seven with only senile cataract group. The upregulated proteins in the RP group were enriched in wound response, while downregulated proteins were enriched in cell adhesion and lens crystallins. Receptors of two dramatically upregulated proteins tenascin-C (TNC) and serotransferrin were found expressed in human lens epithelial cells (HLEs). TNC can promote primary HLEs proliferation and cell line HLE-B3 migration. This study indicates aqueous humor proteomic analysis serves as an effective way to unveil the pathogenesis of RP complications. TNC is a potential target of stimulating HLEs proliferation in RP concomitant cataract patients that worth further research.

Advanced glycation end products in human diabetic lens capsules.

Advanced glycation end products (AGEs) accumulate with age in human lens capsules. AGEs in lens capsules potentiate the transforming growth factor beta-2-mediated mesenchymal transition of lens epithelial cells, which suggests that they play a role in posterior capsule opacification after cataract surgery. We measured AGEs by liquid chromatography-mass spectrometry in capsulorhexis specimens obtained during cataract surgery from nondiabetic and diabetic patients with and without established retinopathy. Our data showed that the levels of most AGEs (12 out of 13 measured) were unaltered in diabetic patients and diabetic patients with retinopathy compared to nondiabetic patients. There was one exception: glucosepane, which was significantly higher in diabetic patients, both with (6.85 pmol/µmol OH-proline) and without retinopathy (8.32 pmol/µmol OH-proline), than in nondiabetic patients (4.01 pmol/µmol OH-proline). Our study provides an explanation for the similar incidence of posterior capsule opacification between nondiabetic and diabetic cataract patients observed in several studies.

The effect of sex on the mouse lens transcriptome.

The transcriptome of mammalian tissues differs between males and females, and these differences can change across the lifespan, likely regulating known sexual dimorphisms in disease prevalence and severity. Cataract, the most prevalent disease of the ocular lens, occurs at similar rates in young individuals, but its incidence is elevated in older women compared to men of the same age. However, the influence of sex on the lens transcriptome was unknown. RNAseq based transcriptomic profiling of young adult C57BL/6J mouse lens epithelial and fiber cells revealed that few genes are differentially expressed between the sexes. In contrast, lens cells from aged (24 month old) male and female C57BL/6J mice differentially expressed many genes, including several whose expression is lens preferred. Like cataracts, posterior capsular opacification (PCO), a major sequela of cataract surgery, may also be more prevalent in women. Lens epithelial cells isolated from mouse eyes 24 h after lens fiber cell removal exhibited numerous transcriptomic differences between the sexes, including genes implicated in complement cascades and extracellular matrix regulation, and these differences are much more pronounced in aged mice than in young mice. These results provide an unbiased basis for future studies on how sex affects the lens response to aging, cataract development, and cataract surgery.

Cataract Surgery Volumes and Complications per Surgeon and Clinical Unit: Data from the Swedish National Cataract Register 2007 to 2016.

PURPOSE: To investigate the change in proportion of high-volume cataract surgeons during the period 2007 to 2016 and determine the impact of operation volume per surgeon and clinical unit on the rate of capsule complications. DESIGN: Retrospective, register-based study. PARTICIPANTS: Patients undergoing and surgeons performing cataract surgery at Swedish ophthalmologic departments 2007-2016. METHODS: All cataract procedures performed during a 10-year period were analyzed, and the change in operation volume of individual surgeons over time was determined. The yearly incidence of capsule complications was correlated to the operation volume of individual surgeons and clinical units. MAIN OUTCOME MEASURES: The number of cataract procedures yearly per surgeon and clinical unit, proportion of capsule complications, and change over time in operation volume and complication rate. RESULTS: The proportion of high-volume (≥500 procedures yearly) and very high-volume (≥1000 procedures yearly) surgeons increased from 15.0% to 34.0% and 2.1% to 10.9%, respectively (P < 0.001 for both categories). The proportion of all cataract procedures performed by high-volume surgeons was 36.9% in 2007, increasing to 68.1% in 2016. The yearly incidence of capsule complications decreased with increasing number of procedures; from a mean of 2.15% (standard deviation [SD], 3.17) for low-volume surgeons (10-99 procedures/year) to 1.32% (1.28) for medium-volume (100-499 procedures/year) surgeons and 0.59% (0.49) for high-volume surgeons (P = 0.016). Preoperative best-corrected visual acuity was significantly better in eyes operated on by high-volume and very high-volume cataract surgeons; the median best-corrected visual acuity (BCVA) was 0.5 (decimal) compared with a BCVA of 0.4 for patients who had their surgery performed by low- or medium-volume surgeons (overall P < 0.001). No significant difference in rate of capsule complications was seen between clinical units with high or low operation volume (P = 0.804). The overall incidence of capsule complications decreased gradually from 1.5% in 2007 to 0.8% in 2016, and preoperative BCVA increased from 0.46±0.10 (logarithm of the minimum angle of resolution) to 0.40±0.05 (P = 0.030). CONCLUSIONS: There is a strong association of rate of capsule complications with operation volume of individual surgeons but not with operation volume of individual clinical units. The decreased rate of capsule complications seen between 2007 and 2016 may be explained in part by a dramatic increase in the proportion of high-volume cataract surgeons during the period.

Altered unfolded protein response and proteasome impairment in pseudoexfoliation pathogenesis.

Pseudoexfoliation (PEX), an ocular disorder involving deposition of proteinaceous fibrils on the surface of anterior eye tissues, is a major contributing factor to worldwide glaucoma. Excessive production and accumulation of fibrillar materials in PEX could be an indication of proteostasis imbalance. This study aims at investigating the differential expression of various genes involved in unfolded protein response and ubiquitin proteasome pathway in pseudoexfoliation (PEX) patients compared to non-PEX controls using lens capsule tissue as the study material. The custom RT2 Profiler PCR array was used to identify a set of stress-related candidate genes that were differentially expressed in PEX. The expression of the highly deregulated genes was validated by qRT-PCR and subsequently their protein expression was checked through immunoblotting and immunostaining. Proteasome-Glo based assay and TUNEL assay were employed to detect specific proteasomal activity and apoptotic activity, respectively in the study subjects. Increased ER stress markers, Synoviolin1, Eukaryotic initiation factor 2-alpha kinase 3, DnaJ (Hsp40) homolog, subfamily B, member 11, Caspase 12, Heat shock 70 kDa protein 5, Heat shock 60 kDa protein 1 and Calnexin were observed in the lens capsule of PEX individuals compared to age-matched controls. On the other hand, increased ubiquitin B mRNA expression followed by significant downregulation of proteasome subunits; 26 S proteasome non-ATPase regulatory subunit 1, and proteasome subunit alpha-type 5 was found in pseudoexfoliation syndrome (PEXS) individuals. Decrease in chymotrypsin-like proteasome activity and increased apoptosis were also observed in PEX subjects. The present findings provide evidence for alterations in endoplasmic reticulum-related stress response and ubiquitin proteasome function in lens capsule of PEX individuals. Altogether, our study has identified deregulated expression of candidate genes in ER-UPR pathway and implicates proteasome impairment as a causative factor in PEX pathogenesis.

AIR/FLUID-DROPPING TECHNIQUE FOR INTRACAPSULAR DISTILLED WATER APPLICATION: A Vitrectomy Approach for Selective Targeting of Lens Epithelial Cells.

PURPOSE: We describe a simplified technique of intracapsular distilled water application for targeting lens epithelial cells using vitrectomy approach of fluid-air exchange and to evaluate the reliability and safety of this technique. METHODS: Consecutive patients with cataract were randomly assigned to treatment group and control group. After the nucleus removal and cortical aspiration, the space of anterior chamber and capsular bag were maintained with continuous infusion of sterile air by using fluid-air exchange technique through side-port incision. Distilled water was dropped into the capsular bag using a specially designed syringe. A concave air-fluid surface (a physical phenomenon) insured the contact of distilled water with the inner surface of the capsule without overflowing from the bag. The distilled water remained in place for 3 minutes and was then removed by the syringe. RESULTS: No intraoperative surgical complication was observed, and no damage to adjacent intraocular structures was observed during the postoperative follow-up. There was no statistical difference of corneal endothelial cell loss between the treatment group and the control group. Histological study confirmed damage to the lens epithelial cells from anterior capsular specimens treated by the technique. CONCLUSION: The simplified technique using vitrectomy approach is safe and specific for targeting lens epithelial cells without associated complications.

Hyperopic shift caused by capsule contraction syndrome after microincision foldable intraocular Lens implantation: case series.

BACKGROUND: Increasing interest in microincision cataract surgery has led to the use of more flexible intraocular lens (IOL). Flexible IOL may cause more IOL deformation and refractive error when capsule contraction syndrome (CCS) occurred. In this retrospective observational case series study, the aim was to report four cases of hyperopic shift caused by CCS after phacoemulsification with microincision foldable intraocular lens implantation. CASE PRESENTATION: All of four patients underwent phacoemulsification and in-the-bag implantation of an Akreos MI60 (Bausch and Lomb) IOL from 2010 to 2016 in our clinic. These patients had been diagnosed with CCS and had undergone Nd:YAG laser anterior capsulotomy. The mean age of the patients with CCS was 66.8 ± 6.7 years and the mean time for development of CCS after the cataract surgery was 9.3 ± 6.9 months. The mean spherical equivalent (SE) value at the time of the CCS diagnosis was 0.88 ± 0.91 D, which had shown a hyperopic shift compared to the SE value of - 0.91 ± 1.29 D after cataract surgery. The mean SE decreased by - 0.47 ± 1.14 D after Nd:YAG laser anterior capsulotomy. The mean age, axial length, anterior chamber depth, and preoperative SE were not significantly different between the patient with CCS and the patients without CCS. CONCLUSIONS: In the case of IOL implantation with flexible materials in microincision cataract surgery, CCS can cause a hyperopic shift. Refractive error caused by CCS can be effectively corrected by Nd:YAG laser anterior capsulotomy.

Case Series: Late Postoperative Capsular Block Syndrome Causing Reduced Vision Years After Uncomplicated Cataract Surgery.

SIGNIFICANCE: Late postoperative capsular block syndrome is a treatable complication presenting months to years after cataract surgery using continuous curvilinear anterior capsulorhexis and a posterior chamber intraocular lens implantation. Patients may present to optometric practices because of symptom onset significantly after the immediate post-operative period. PURPOSE: The purpose of this study was to describe the defining clinical features, proposed pathophysiology, and treatment of late postoperative capsular block syndrome. Case 1 was a 68-year-old man who presented with a sudden onset of blurry vision in the right eye 2 years after uncomplicated cataract surgery. Clinical examination revealed turbid fluid distending the posterior lens capsule, a 2-D myopic shift, and an absence of intraocular inflammation. Laser posterior capsulotomy successfully released the trapped fluid and reversed the myopic shift without complication. Case 2 was a 67-year-old man who presented with a gradual onset of hazy vision in the right eye 7 years after uncomplicated cataract surgery. Cloudy fluid was observed to be filling the space between the intraocular lens and the posterior lens capsule, and the refractive error was stable. The fluid was liberated and visual function was restored with uncomplicated laser posterior capsulotomy. CONCLUSIONS: Patients with late postoperative capsular block syndrome may present with blurry vision months to years after cataract surgery performed with continuous curvilinear capsulorhexis and posterior capsule intraocular lens implantation. The defining clinical sign is entrapment of turbid fluid between the intraocular lens and the posterior capsule that may result in reduced vision or refractive error shift. Late postoperative capsular block syndrome is distinguishable from other late complications of cataract surgery, including delayed endophthalmitis or phacoantigenic uveitis, by lack of concurrent robust ocular inflammation.

Hook and flip technique: for phacoemulsification in non-rotating nuclei and posterior polar cataracts.

PURPOSE: We put forward a physical levitation method to hook and flip the chopped nuclear fragments that could not be solely drawn by vacuum during phacoemulsification, due to various reasons such as a non-rotating nuclei or posterior polar cataracts where hydrodissection was unsuccessful or contra-indicated, respectively. METHOD: A Sinskey hook is insinuated through the crack of the divided nuclei into a plane behind the nuclear pie to 'hook and flip' the chopped piece, heading it towards the phacoemulsification probe. This simple step disassembles the nuclear chunk, thereby creating space to facilitate the dismantling of the rest of the fragments. The remnant epinuclear cushion guards the posterior capsule, mitigating the chances of serious intra-operative complications. RESULT: We have employed this technique in 17 eyes during similar situations. No specific intra-operative complications were observed; all surgeries were uneventful. A Sinskey hook utilised for this step ensures safety and familiarity, none encountered posterior capsular rent. This technique not only eases the surgery, but also decreases the anticipated intra-operative and post-operative complications. CONCLUSION: 'Hook and flip technique' thus proves useful whenever dismantling difficulties are encountered during phacoemulsification.

Bioinorganic Markers of a Loss of the Crystalline Lens Capsule Barrier Properties and Consequent Age-Related Cataract Development.

The age-related cataract development consequent upon a loss of the lens capsule barrier properties proved to be associated with accumulation of sodium, calcium, phosphorus and potassium. For the first time the use of spatial cluster and correlation analyses showed that the physical light scattering in the crystalline lens volume depends on changes in the lens matter elemental composition. The fields of elevated concentrations of sodium, calcium, phosphorus, potassium and chlorine conformed to the lens capsule geometry and their clustering was similar to that of opacity fields in the lens body. The accumulation geometry of the elements in the lens body that are commonly seen in the aqueous humor of the anterior chamber, can be considered evidence for excessive transitioning of their compounds through the lens capsule shell, while its spatial connection with transparency changes-proof of participation in cataractogenesis.

Age-related aqueous humor (AH) and lens epithelial cell/capsule protein carbonylation and AH protein concentration in cataract patients who have pseudoexfoliative diseases.

Purpose: The aim of this study is to investigate the age-correlation of oxidative stress (OS, assessed by the accumulative OS damage marker protein carbonyls) in aqueous humour (AH; together with protein concentration) and lens epithelial cells plus capsule (LECs/capsule) in patients with cataract (CAT), and also suffering from pseudoexfoliation syndrome (PEX), primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PXG). Methods: AH samples from 78 male/female patients (21, 20, 19 and 18 with CAT, PEX, PXG, and POAG, respectively), and LECs/capsule samples from 104 male/female patients (34, 32, 18, and 20 with CAT, PEX, PXG and POAG, respectively) were collected during phacoemulsification CAT surgery. Average protein carbonyl concentrations were measured in patients grouped in 5-year age intervals (ranging from 56-60 to 86-90). The non-overlapping age ranges and numbers of the tested subjects did not allow comparative follow up studies for the tested diseases. Results: There is an age-dependent increase of protein carbonyls in AH (nmol mg-1 protein and ml-1), and in the order CAT

Novel protein constituents of pathological ocular pseudoexfoliation syndrome deposits identified with mass spectrometry.

Purpose: Pseudoexfoliation (PEX) syndrome is an age-related progressive disease of the extracellular matrix with ocular manifestations. PEX is clinically diagnosed by the presence of extracellular exfoliative deposits on the anterior surface of the ocular lens. PEX syndrome is a major risk factor for developing glaucoma, the leading cause of irreversible blindness in the world, and is often associated with the development of cataract. PEX reportedly coexists with Alzheimer disease and increases the risk of heart disease and stroke. PEX material deposited on the anterior surface of the ocular lens is highly proteinaceous, complex, and insoluble, making deciphering the protein composition of the material challenging. Thus, to date, only a small proportion of the protein composition of PEX material is known. The aim of this study was to decipher the protein composition of pathological PEX material deposited on the ocular lens in patients and advance the understanding of pathophysiology of PEX syndrome. Methods: Liquid-chromatography and tandem mass spectrometry (LC-MS/MS) was employed to discover novel proteins in extracts of neat PEX material surgically isolated from patients (n = 4) with PEX syndrome undergoing cataract surgery. A sub-set of the identified proteins was validated with immunohistochemistry using lens capsule specimens from independent patients (n=3); lens capsules from patients with cataract but without PEX syndrome were used as controls (n=4). Expression of transcripts of the validated proteins in the human lens epithelium was analyzed with reverse transcription PCR (RT-PCR). Functional relationships among the proteins identified in this study and genes and proteins previously implicated in the disease were bioinformatically determined using InnateDB. Results: Peptides corresponding to 66 proteins, including ten proteins previously known to be present in PEX material, were identified. Thirteen newly identified proteins were chosen for validation. Of those proteins, 12 were found to be genuine components of the material. The novel protein constituents include apolipoproteins (APOA1 and APOA4), stress response proteins (CRYAA and PRDX2), and blood-related proteins (fibrinogen and hemoglobin subunits), including iron-free hemoglobin. The gene expression data suggest that the identified stress-response proteins and hemoglobin are contributed by the lens epithelium and apolipoproteins and fibrinogen by the aqueous humor to the PEX material. Pathway analysis of the identified novel protein constituents and genes or proteins previously implicated in the disease reiterated the involvement of extracellular matrix organization and degradation, elastic fiber formation, and complement cascade in PEX syndrome. Network analysis suggested a central role of fibronectin in the pathophysiology of the disease. The identified novel protein constituents of PEX material also shed light on the molecular basis of the association of PEX syndrome with heart disease, stroke, and Alzheimer disease. Conclusions: This study expands the understanding of the protein composition of pathological PEX material deposited on the ocular lens in patients with PEX syndrome and provides useful insights into the pathophysiology of this disease. This study together with the previous study by our group (Sharma et al. Experimental Eye Research 2009;89(4):479-85) demonstrate that using neat PEX material, devoid of the underlying lens capsule, for proteomics analysis is an effective approach for deciphering the protein composition of complex and highly insoluble extracellular pathological ocular deposits present in patients with PEX syndrome.

Effect of number and position of intraocular lens haptics on anterior capsule contraction: a randomized, prospective trial.

BACKGROUND: The present study aimed to evaluate the degree of anterior capsule contraction (capsulorhexis contraction) with three different single-piece, hydrophilic acrylic intraocular lenses (IOLs). METHODS: Patients were prospectively randomized to be implanted with one of three types of IOLs during cataract surgery: the Ophtec Precizon (IOL A), the Lucid Korea Microflex (IOL B), and the Carl Zeiss Asphina (IOL C). One week, 2 weeks, and 6 months after surgery, the area of the anterior capsule opening was measured using digital retro-illumination images after dilation of the pupil. The data were then evaluated using POCOman software. RESULTS: The study included 236 eyes of 202 patients. The area of the anterior capsule opening reduced by 3.53 ± 3.31 mm (17.06% ± 15.99%) between 1 week and 2 months post-operatively in the IOL A group, by 0.62 ± 1.32 mm (2.87% ± 6.03%) in the IOL B group, and by 1.09 ± 1.53 mm (4.72% ± 6.10%) in the IOL C group. The IOL B group showed minimal anterior capsule contraction 2 months after surgery (p < 0.001). CONCLUSIONS: IOLs with a four-plate haptic design (IOL B) showed more anterior capsular stability than those with a two-loop plate haptic (IOL A) or two-plate haptic (IOL C) design. The number and position of haptics in a capsular bag may affect anterior capsule contraction. We assume that supporting the zonules evenly may play a role in anterior capsular stability. TRIAL REGISTRATION: Current Controlled Trials ISRCTN76566080 , Retrospectively registered (Date of registration: 14 Feb 2018).