[The role of citicoline in glaucoma]. / Bedeutung von Citicolin bei der Glaukomerkrankung.

BACKGROUND: In recent years, many experimental and clinical studies have shown that in glaucoma, neuronal degeneration occurs not only at the level of the retina and optic nerve, but also along the entire visual pathway and the brain. OBJECTIVE: This article presents the neuroprotective effects of citicoline and their mechanisms in glaucoma disease. MATERIALS AND METHODS: The relevance of citicoline is explained against the background of neuroanatomy, neuroimaging, and the pathogenesis of glaucoma. Data from experimental and clinical studies are presented and a conclusion is drawn for clinical application. RESULTS: Citicoline has a neuroprotective effect via mechanisms relevant to glaucoma. The neuroprotective effect of citicoline in open-angle glaucoma can be demonstrated functionally and morphologically. It is independent of the glaucoma damage and intraocular pressure, and usually occurs only after 1 year. The effects of oral citicoline occur at a daily dose of 500-1000 mg. Citicoline can be taken permanently or in cycles. No side effects occurred in the studies when taking citicoline. Citicoline can improve cognitive performance and thus treatment adherence as well as quality of life in glaucoma patients. CONCLUSION: This relatively old nootropic drug, which is now marketed as a food supplement, seems to be a valuable addition to conventional treatment and also a rational option for prophylaxis of open-angle glaucoma.

Aqueous humor selenium level and open-angle glaucoma.

PURPOSE: Selenium supplementation was seen to be linked to glaucoma disease in a previous study (Lillico A. JE, Reid M et al. (2002) Selenium Supplementation and Risk of Glaucoma in the NPC trial University of Arizona, Tucson, AZ., Arizona Cancer Center). As aqueous humor levels of selenium seemed to be associated with primary open-angle glaucoma (POAG), the aim of this study was to analyze concentrations of selenium in aqueous humor samples of patients with POAG and pseudoexfoliation glaucoma (PEXG) in comparison to normal samples. PATIENTS AND METHODS: Thirty-eight aqueous humor samples from patients undergoing cataract surgery were collected: Eleven patients with PEXG (age 65.8 ±â€¯10.69, female 6, male 5), 12 patients with POAG (age 65.3 ±â€¯10.50, female 7, male 5) and 15 patients without glaucoma (age 70.9 ±â€¯12.83, female 10, male 5, controls). Aqueous humor levels of selenium were measured by Flow-Injection-Inductively-Coupled-Plasma-DRC-Mass-Spectrometry (ICP-DRC-MS). RESULTS: Maximum likelihood estimation of the least squares means (LS-means) and the relative 95% confidence limits of selenium aqueous humor levels were 6.90 ±â€¯1.03 µg/L (control), 6.74 ±â€¯1.14 µg/L (POAG) and 8.25 ±â€¯1.18 µg/L (PEXG). The data were modeled using a generalized linear model (GLM) analysis, where selenium was set as dependent variable. The model was corrected for group differences in age and gender. The data show no differences among all the calculated differences between the least square means (LS means), taking in consideration the simultaneous 95% confidence limit and the multiple comparison tests with Tukey-Cramer adjustment. The evaluation of the model disclosed that POAG and PEXG patients had no significantly different aqueous humor selenium concentrations compared to controls and to each other. However, the quantile regression analysis of selenium aqueous humor levels showed differences in quantiles for open-angle glaucoma patients considering age and gender. CONCLUSION: As no significant difference in aqueous humor concentration of selenium was detected between open-angle glaucoma and controls, however, quantile analysis showed differences in quantiles levels for different age ranges in open-angle glaucoma patients, the trace element selenium seemed to be linked to glaucoma disease, yet not in a major role.

Role of Bone Morphogenetic Protein 7 (BMP7) in the Modulation of Corneal Stromal and Epithelial Cell Functions.

In the cornea, healing of the wounded avascular surface is an intricate process comprising the involvement of epithelial, stromal and neuronal cell interactions. These interactions result to the release of various growth factors that play prominent roles during corneal wound healing response. Bone morphogenetic proteins (BMPs) are unique multi-functional potent growth factors of the transforming growth factor-beta (TGF-β) superfamily. Treatment of corneal epithelial cells with substance P and nerve growth factor resulted to an increase in the expression of BMP7 mRNA. Since BMP7 is known to modulate the process of corneal wound healing, in this present study, we investigated the influence of exogenous rhBMP7 on human corneal epithelial cell and stromal cell (SFs) function. To obtain a high-fidelity expression profiling of activated biomarkers and pathways, transcriptome-wide gene-level expression profiling of epithelial cells in the presence of BMP7 was performed. Gene ontology analysis shows BMP7 stimulation activated TGF-β signaling and cell cycle pathways, whereas biological processes related to cell cycle, microtubule and intermediate filament cytoskeleton organization were significantly impacted in corneal epithelial cells. Scratch wound healing assay showed increased motility and migration of BMP7 treated epithelial cells. BMP7 stimulation studies show activation of MAPK cascade proteins in epithelial cells and SFs. Similarly, a difference in the expression of claudin, Zink finger E-box-binding homeobox 1 was observed along with phosphorylation levels of cofilin in epithelial cells. Stimulation of SFs with BMP7 activated them with increased expression of α-smooth muscle actin. In addition, an elevated phosphorylation of epidermal growth factor receptor following BMP7 stimulation was also observed both in corneal epithelial cells and SFs. Based on our transcriptome analysis data on epithelial cells and the results obtained in SFs, we conclude that BMP7 contributes to epithelial-to-mesenchymal transition-like responses and plays a role equivalent to TGF-β in the course of corneal wound healing.

Role of Corneal Stromal Cells on Epithelial Cell Function during Wound Healing.

Following injury, corneal stromal keratocytes transform into repair-phenotype of activated stromal fibroblasts (SFs) and participate in wound repair. Simultaneously, ongoing bi-directional communications between corneal stromal-epithelial cells also play a vital role in mediating the process of wound healing. Factors produced by stromal cells are known to induce proliferation, differentiation, and motility of corneal epithelial cells, which are also subsequently the main processes that occur during wound healing. In this context, the present study aims to investigate the effect of SFs conditioned medium (SFCM) on corneal epithelial cell function along with substance P (SP). Antibody microarrays were employed to profile differentially expressed cell surface markers and cytokines in the presence of SFCM and SP. Antibody microarray data revealed enhanced expression of the ITGB1 in corneal epithelial cells following stimulation with SP whereas SFCM induced abundant expression of IL-8, ITGB1, PD1L1, PECA1, IL-15, BDNF, ICAM1, CD8A, CD44 and NTF4. All these proteins have either direct or indirect roles in epithelial cell growth, movement and adhesion related signaling cascades during tissue regeneration. We also observed activation of MAPK signaling pathway along with increased expression of focal adhesion kinase (FAK), paxillin, vimentin, ß-catenin and vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Additionally, epithelial-to-mesenchymal transition (EMT) regulating transcription factors Slug and ZEB1 expression were enhanced in the presence of SFCM. SP enriched the expression of integrin subunits α4, α5, αV, ß1 and ß3 whereas SFCM increased α4, α5, αV, ß1 and ß5 integrin subunits. We also observed increased expression of Serpin E1 following SP and SFCM treatment. Wound healing scratch assay revealed enhanced migration of epithelial cells following the addition of SFCM. Taken together, we conclude that SFCM-mediated sustained activation of ZEB1, Slug in combination with upregulated migration-associated integrins and ERK (Extracellular signal-regulated kinase)-FAK-paxillin axis, may lead to induce type 2 EMT-like changes during corneal epithelial wound healing.

Levels of aqueous humor trace elements in patients with open-angle glaucoma.

PURPOSE: Trace elements might play a role in the complex multifactorial pathogenesis of open-angle glaucoma. The aim of this study was to analyze concentrations of trace elements in aqueous humor samples of patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEXG). PATIENTS AND METHODS: Thirty-three aqueous humor samples were obtained from patients undergoing cataract surgery: 12 patients with POAG (age 65.3±10.50, female 8, male 4), 10 patients with PEXG (age 65.9±11.27, female 6, male 4) and 11 patients without glaucoma (age 69.5±13.70, female 7, male 4) serving as controls. Aqueous humor levels of cadmium, iron, manganese, cobalt, copper and zinc were measured by Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS). RESULTS: From the statistical evaluation, we observed that patients with POAG had significantly higher aqueous humor levels of zinc (p=0.006) compared to controls. Increased aqueous humor levels of zinc were also observed in patients with PEXG in relation to control (p=0.0006). For iron we observed a significantly reduction in PEXG compared to control (p=0.002) and a significant difference between POAG and PEXG (p=0.0091). No significant differences were observed in aqueous humor levels of manganese, cobalt, copper, cadmium between glaucoma and control patients. No differences were seen for iron (POAG vs. controls). Analysis of trace element ratios was added. CONCLUSION: Significant differences in aqueous humor levels of zinc and iron between glaucoma and control patients support the hypothesis that these trace elements are involved in the pathogenesis of open-angle glaucoma.

Outcomes of Sutureless Iris-Claw Lens Implantation.

Purpose. To evaluate the indications, refraction, and visual and safety outcomes of iris-claw intraocular lens implanted retropupillary with sutureless technique during primary or secondary operation. Methods. Retrospective study of case series. The Haigis formula was used to calculate intraocular lens power. In all cases the wound was closed without suturing. Results. The study comprised 47 eyes. The mean follow-up time was 15.9 months (SD 12.2). The mean preoperative CDVA was 0.25 (SD 0.21). The final mean CDVA was 0.46 (SD 0.27). No hypotony or need for wound suturing was observed postoperatively. Mean postoperative refractive error was -0.27 Dsph (-3.87 Dsph to +2.85 Dsph; median 0.0, SD 1.28). The mean postoperative astigmatism was -1.82 Dcyl (min -0.25, max -5.5; median -1.25, SD 1.07). Postoperative complications were observed in 10 eyes. The most common complication was ovalization of the iris, which was observed in 8 eyes. The mean operation time was 35.9 min (min 11 min, max 79 min; median 34, SD 15.4). Conclusion. Retropupilary iris-claw intraocular lens (IOL) implantation with sutureless wound closing is an easy and fast method, ensuring good refractive outcome and a low risk of complication. The Haigis formula proved to be predictable in postoperative refraction.

Surgical treatment of open globe trauma complicated with the presence of an intraocular foreign body.

BACKGROUND: Open globe injuries complicated with the presence of an intraocular foreign body constitute a vision threatening condition. PURPOSE: To present the results of pars plana vitrectomy in patients with intraocular foreign body. MATERIAL AND METHODS: Medical records of 22 patients were analyzed. Retrospective analysis of data included visual acuity, age, gender and type of injury. RESULTS: All patients were men and the mean age was 37 years. All injuries occurred while working with a hammer. All patients were treated with pars plana vitrectomy combined with intraocular foreign body removal and internal limiting membrane peeling. The visual acuities improved in 9 cases (41%), in 13 cases (59%) the deterioration of visual acuity was observed, no eye was enucleated. In 14 eyes pars plana vitrectomy was combined with lens removal, in 14 eyes silicone oil was used as a tamponade. CONCLUSIONS: Surgical intervention with pars plana vitrectomy combined with intraocular foreign body removal and cataract extraction may preserve severely traumatized eyes and maintain or even improve vision. ocular trauma, vitrectomy, intraocular foreign body.

Short-term fluctuation of intraocular pressure is higher in patients with pseudoexfoliation syndrome despite similar mean intraocular pressure: a retrospective case-control study.

PURPOSE: Higher levels of short-term fluctuation of intraocular pressure (IOP) are characteristic of pseudoexfoliation syndrome (PEX). However, it is not known whether they are just a side effect of the higher mean intraocular pressure (IOP) or an independent feature. The purpose of this study was to compare short-term fluctuation of IOP between eyes with PEX and control eyes that were matched as closely as possible for mean IOP. METHODS: In this retrospective case-control study, all patients with confirmed PEX were identified from the database of the Erlangen Glaucoma Registry. From the same database, matched control eyes with similar treatment, age, glaucoma stage, and mean IOP were identified. For each patient, data from multiple extended diurnal IOP profiles were available. RESULTS: Seventy-eight eyes were included in the study (39 with PEX and 39 matched control eyes). Although a very close match was achieved, a small but statistically significant difference in mean IOP was still present, but this did not seem to explain the differences in IOP fluctuation levels. Eyes with PEX had significantly higher short-term IOP fluctuations (SD of IOP and range of IOP). CONCLUSIONS: The higher levels of short-term fluctuation in IOP appear to be an independent feature of PEX and not merely a secondary effect of the higher mean IOP. We suggest that this may have practical implications, even if IOP fluctuation levels should not prove to be an independent risk factor for development/progression of glaucoma, because more frequent measurements are needed in these patients to obtain good estimates of mean IOP and changes in IOP under treatment.

Longitudinal stability of the diurnal rhythm of intraocular pressure in subjects with healthy eyes, ocular hypertension and pigment dispersion syndrome.

BACKGROUND: The diurnal fluctuation of intraocular pressure may be relevant in glaucoma. The aim of this study was to find out whether the timing of diurnal fluctuation is stable over the years. METHODS: Long-term IOP data from the Erlangen Glaucoma Registry, consisting of several annual extended diurnal IOP profiles for each patient, was retrospectively analyzed. Normal subjects, patients with ocular hypertension and with pigment dispersion syndrome were included because these subjects had not been treated with antiglaucomatous medications at the time of data acquisition. A cosine curve was fitted to the IOP data and the stability of individual rhythms over the years was tested using the Rayleigh test. To compare the peak times among groups, means were calculated only from subjects with a significant Rayleigh test. RESULTS: Of the fifty-two eligible subjects, a total of 364 extended diurnal IOP profiles measured in a sitting position had been collected over a period of 114 ± 39 months. The Rayleigh test indicated intraindividual stability of phase timing only in 19 subjects (36%). In subjects with pigment dispersions syndrome, peak IOP occurred on average two hours and seven minutes later during the day compared with subjects without this condition (p = 0.05). CONCLUSIONS: Fitting of cosine curves to the clinical IOP profiles was generally feasible, although careful interpretation is warranted due to lack of measurements in supine position and between midnight and 7 am. The interesting observation of a phase lag in eyes with pigment dispersion syndrome warrants confirmation and exploration in future prospective studies. The analysis of the IOP data showed no stable individual rhythm in the long term in a majority of patients.

Time course of induced astigmatism after canaloplasty.

PURPOSE: To study the changes in astigmatism after canaloplasty and to analyze its correlation with long-term intraocular pressure (IOP) results. METHODS: Twenty-six eyes of 26 consecutive patients with primary open-angle glaucoma (n=14) and pseudoexfoliative glaucoma (n=12) undergoing canaloplasty were included in this retrospective study. Canaloplasty comprised of 360-degree catheterisation of Schlemm canal by means of a flexible microcatheter with distension of the canal by 2 tensioning 10-0 polypropylene sutures. Primary outcome measures included IOP, glaucoma medication usage, astigmatism, and adverse events at 2, 4, 12, and 24 weeks postoperatively. RESULTS: The mean preoperative IOP was 21.1±5.8 mm Hg. The mean IOP decreased to 14.25 ±4.3 mm Hg at 6 months. Mean astigmatism preoperatively was 0.77±0.5 D, which increased to 3.3±1.7 D at 2 weeks postoperatively (P≤0.05; Wilcoxon-test). Thereafter, the astigmatism underwent a spontaneous decline, reaching 1.9±0.8 D at 4 weeks and 1.2±0.74 D at 12 weeks postoperatively. Best-corrected visual acuity did not change significantly. Six months after canaloplasty, mean astigmatism reached the preoperative range of 0.86±0.52 D. Astigmatism at 2 weeks correlated significantly and inversely with IOP at 6 months (r=0.59, P=0.005; Spearman). CONCLUSIONS: The change of astigmatism after canaloplasty follows a clear time course with a maximum at 2 weeks reaching preoperative values at 6 months. The amount of surgically induced astigmatism might be helpful to predict outcome of canaloplasty in terms of IOP reduction.

Presence and distribution of L-kynurenine aminotransferases immunoreactivity in human cataractous lenses.

PURPOSE: To investigate the presence and distribution of l-kynurenine aminotransferases immunoreactivity in human and animal lenses during cataract formation. METHODS: Immunohistochemistry was conducted using polyclonal antibodies against KAT I, KAT II and KAT III on sections of 26 anterior capsules from patients undergoing surgical treatment of anterior subcapsular cataract (ASC) and 22 cataractous lenses from human eyes enucleated because of choroidal malignant melanoma. Additionally, the eyes of 11-month-old DBA/2J mice (6 eyes) were investigated (with KAT I and II). Ten clear human lenses and four BL6 mice lenses were used as controls. Spatial immunoreactivity patterns of enzymes were compared with Periodic Acid - Schiff (PAS)-stained sections. RESULTS: Immunohistochemical analysis revealed presence of KAT I, KAT II and KAT III in extracellular structures of all studied types of cataract in human eyes showing specific pattern of the stain. In cortical cataract, immunoreactivity was observed on cortical lens fibres. In nuclear cataract, KAT II revealed stronger and diffused staining than KAT I. Additionally, both KAT showed more pronounced staining at the edge of small clefts. In normal human lenses, KAT I, II and III, immunoreactivity was not observed. Presence of KAT I and KAT II in the intercellular substance of DBA/2J mice cataract was observed. In BL6 mice lenses without cataract, only weak KAT I and KAT II staining was observed. CONCLUSIONS: Presence of l-kynurenine aminotransferases in extracellular matrix (ECM) during human cataract formation suggests that products of l-kynurenine pathway might be involved in mechanisms of cataractogenesis.

Levels of aqueous humor trace elements in patients with non-exsudative age-related macular degeneration: a case-control study.

Trace elements might play a role in the complex multifactorial pathogenesis of age-related macular degeneration (AMD). The aim of this study was to measure alterations of trace elements levels in aqueous humor of patients with non-exsudative (dry) AMD. For this pilot study, aqueous humor samples were collected from patients undergoing cataract surgery. 12 patients with dry AMD (age 77.9±6.62, female 8, male 4) and 11 patients without AMD (age 66.6±16.7, female 7, male 4) were included. Aqueous levels of cadmium, cobalt, copper, iron, manganese, selenium, and zinc were measured by use of Flow-Injection-Inductively-Coupled-Plasma-Mass-Spectrometry (FI-ICP-MS), quality controlled with certified standards. Patients with AMD had significantly higher aqueous humor levels of cadmium (median: 0.70 µmol/L, IQR: 0.40-0.84 vs. 0.06 µmol/L; IQR: 0.01-.018; p = 0.002), cobalt (median: 3.1 µmol/L, IQR: 2.62-3.15 vs. 1.17 µmol/L; IQR: 0.95-1.27; p<0.001), iron (median: 311 µmol/L, IQR: 289-329 vs. 129 µmol/L; IQR: 111-145; p<0.001) and zinc (median: 23.1 µmol/L, IQR: 12.9-32.6 vs. 5.1 µmol/L; IQR: 4.4-9.4; p = 0.020) when compared with patients without AMD. Copper levels were significantly reduced in patients with AMD (median: 16.2 µmol/L, IQR: 11.4-31.3 vs. 49.9 µmol/L; IQR: 32.0-.142.0; p = 0.022) when compared to those without. No significant differences were observed in aqueous humor levels of manganese and selenium between patients with and without AMD. After an adjustment for multiple testing, cadmium, cobalt, copper and iron remained a significant factor in GLM models (adjusted for age and gender of the patients) for AMD. Alterations of trace element levels support the hypothesis that cadmium, cobalt, iron, and copper are involved in the pathogenesis of AMD.

Bilateral circumscribed posterior keratoconus: visualization by ultrasound biomicroscopy and slit-scanning topography analysis.

This paper documents a rare nonprogressive developmental disorder-bilateral circumscribed posterior keratoconus-in a 60-year-old man referred for a cataract surgery. For the first time ultrasound biomicroscopy was used to visualise the local anterior bulging of the posterior corneal surface with concomitant thinning of the stroma. The amount of localized posterior depression, corneal thickness and the refractive power of both the posterior and anterior corneal curvature were measured using slit-scanning topography analysis (Orbscan).

[New drug VEGF Trap-Eye--Eylea--and its use in the treatment of age-related macular degeneration, central retinal vein occlusion, diabetic macular edema, and choroidal neovascularization secondary to pathologic myopia]. / Nowy lek VEGF Trap-Eye--Eylea--i jego wykorzystanie w leczeniu zwyrodnienia plamki zwiazanego z wiekiem, zakrzepu zyly srodkowej siatkówki, cukrzycowego obrzeku plamki oraz neowaskularyzacji w przebiegu krótkowrocznosci.

Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of choroidal and retinal neovascularization. Anti-VEGF therapy changed the standard-of-care for ocular disease with neovascularisation. This article presents one promising new drug--VEGF Trap-Eye--and results of clinical trials evaluating its efficacy in the treatment of wet age-related macular degeneration, central retinal vain occlusion, diabetic macular edema and choroidal neovascularization secondary to pathologic myopia.

Frequency dependency of temporal contrast adaptation in normal subjects.

The aim of this study was to determine the influence of temporal frequency of temporal contrast adaptation on contrast sensitivity in healthy subjects. Temporal contrast sensitivities (TCS) were measured monocularly in seven healthy subjects with a modified ERG full-field bowl stimulator at eight different test temporal frequencies (9, 15, 20, 25, 31, 37, 44, 51 Hz) using a two-alternative-forced-choice strategy. Before each presentation of the test stimulus, a 100% contrast adapting flicker stimulus was presented (frequencies: 9, 15, 20, 25, 31, 37, 44, 51, 100 Hz). At each adapting frequency, a complete set of TCSs was measured. All temporal contrast sensitivities decreased with increasing temporal frequencies. Adaptation led to a general temporal contrast sensitivity decrease. Largest adaptation effects were seen at an adaptation frequency of 25 Hz. Reduction of contrast sensitivity was significantly larger at 25 Hz adaptation than at 9 Hz adaptation (t-test of paired samples, Bonferroni corrected). The results of this study showed a general TCS decrease with the largest effect at an adaptation frequency of 25 Hz. This finding indicates that the contrast adaptation probably occurred in the magnocellular-pathway. In future clinical studies adaptation effects could be investigated in patients with reduced temporal contrast sensitivity.

Emerging therapies for the treatment of wet age-related macular degeneration--VEGF Trap-Eye.

Age-related macular degeneration (AMD) is the leading cause of blindness in the industrialized world. The most severe form of this disease is exudative AMD. It accounts for 10% of cases of AMD and is responsible for approximately 90% cases of severe vision loss due to AMD. Anti-vascular endothelial growth factor (VEGF) therapy changed the standard-of-care for this blinding disease. This article presents one promising new drug for the treatment of exudative AMD--VEGF Trap-Eye.

Tumors of the lacrimal drainage system.

Tumors of the lacrimal drainage system are rare, but potentially life-threatening. They comprise a large and variable spectrum of entities grouped into three major categories of primary epithelial, primary nonepithelial and inflammatory lesions. The most common primary epithelial tumors include papilloma, squamous cell carcinoma and transitional cell carcinoma, the most frequent primary nonepithelial tumors fibrous histiocytoma, malignant lymphoma and malignant melanoma, and the most common inflammatory lesions sarcoidosis, Wegener granulomatosis and pyogenic granuloma. This review outlines the incidence, types, management and prognosis of tumors affecting the lacrimal drainage system.

Immunohistochemical identification of kynurenine aminotransferases in corpora amylacea in the human retina and optic nerve.

INTRODUCTION: Corpora amylacea (CAm) occur in the optic nerve and in retinal ageing and degeneration. Cellular expression of L-kynurenine aminotransferases (KAT I and II) in the avian and rodent retina and its changes in retinal development and neurodegeneration have been documented. This study examines KAT I and II immunoreactivity in CAm in the human retina and optic nerve. MATERIAL AND METHODS: Immunohistochemistry was performed using polyclonal antibodies against KAT I and KAT II on sections of 23 human eyes enucleated for malignant uveal melanoma. Occurrence and location of KAT I- or KAT II-stained CAm was compared with PAS-stained sections. RESULTS: KAT I and KAT II expression in CAm has been shown in the retina and optic nerve with similar location to PAS-stained sections. KAT I immunoreactivity was more intense than KAT II and its staining was more pronounced in the retrolaminar part of the optic nerve. Some of the CAm showed only faint KAT II expression and occasionally there was no staining. KAT II revealed no association of staining variability and localisation of CAm. Similarly to animal studies, in the human retina KAT I was observed on Müller cell endfeet while KAT II was expressed in retinal ganglion cells. CONCLUSIONS: Presence of kynurenine aminotransferases in CAm in the human retina and optic nerve suggest that both enzymes may be involved in mechanisms of retinal ageing and neurodegeneration leading to CAm formation.

C677T variant in the methylentetrahydrofolate reductase gene is a genetic risk factor for primary open-angle glaucoma.

PURPOSE: To estimate the prevalence of C677T single nucleotide polymorphism in the 5,10-methylentetrahydrofolate reductase (MTHFR) gene in primary open-angle glaucoma (POAG) and pseudoexfoliation open-angle glaucoma (PEXG). DESIGN: Case-control study METHODS: MTHFR was assessed in 147 patients (76 POAG, 71 PEXG) and 71 control subjects with cataract. Associations of genotypes were assessed by Armitage's trend test and the corresponding odds ratio (OR) for allele positivity with 95% confidence interval (CI). RESULTS: We observed significant evidence of a higher prevalence of C677T in POAG (9% homozygote, 49% heterozygote, 42% wildtype, P = .01, OR = 2.38, 95% CI 1.23-4.62), but not in PEXG (9% homozygote, 41% heterozygote, 50% wildtype, P = .09, OR = 1.78, 95% CI 0.91-3.50) compared with the controls (3% homozygote, 34% heterozygote, 63% wildtype). CONCLUSIONS: The MTHFR C677T variant leading to moderate hyperhomocysteinemia may play a role in the pathogenesis of POAG acting as a genetic risk factor.

Comparative effects of TGF-beta 1 and TGF-beta 2 on extracellular matrix production, proliferation, migration, and collagen contraction of human Tenon's capsule fibroblasts in pseudoexfoliation and primary open-angle glaucoma.

PURPOSE: To comparatively investigate the effects of TGF-beta(1) and TGF-beta(2) on extracellular matrix production, proliferation, migration, and collagen contraction of cultured human Tenon's capsule fibroblasts derived from patients with pseudoexfoliation (PEX) syndrome, PEX glaucoma, primary open-angle glaucoma (POAG), and cataract. METHODS: Tenon's capsule fibroblasts obtained from four groups of patients were cultured and stimulated with different concentrations (0.1-10 ng ml(-1)) of TGF-beta(1) or TGF-beta(2) for up to 14 days. Cell proliferation was determined with the WST-1 colorimetric assay, cell migration by using the Transwell assay system, and collagen contraction by computerised analysis of three-dimensional collagen lattices and immunohistochemistry for alpha-smooth muscle actin expression. Expression and synthesis of extracellular matrix components (fibronectin, collagen types I and III) was assessed by enzyme-linked immunosorbent assays, by real-time RT-PCR, and by transmission electron microscopy. RESULTS: Both TGF-beta(1) and TGF-beta(2) in pathophysiological concentrations of 0.1-5 ng ml(-1) stimulated cell proliferation, migration, collagen contraction, alpha-smooth muscle actin expression as well as mRNA expression and secretion of fibronectin, collagen type I, and collagen type III by Tenon's fibroblasts derived from all groups of patients. TGF-beta stimulation occurred in a concentration-dependent manner with different peak activities associated with different fibroblast functions. There was some variability among the different groups of patients with an increased response of cells derived from PEX and POAG patients as compared to cataract patients. Although no statistically significant differences were found between both TGF-beta isoforms, TGF-beta(1) had a more pronounced stimulatory effect on expression and synthesis of extracellular matrix components including the production of elastic microfibrils, particularly in cells derived from patients with PEX syndrome/glaucoma. CONCLUSIONS: These findings suggest a significant contribution of TGF-beta(1) in addition to TGF-beta(2) to the conjunctival scarring process following glaucoma filtration surgery. Due to its pronounced fibrogenic potential, TGF-beta(1) may become another focus for targeting drug therapy, particularly in patients with PEX glaucoma.