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Climatic droplet keratopathy (CDK) is an acquired and potentially handicapping cornea degenerative disease that is highly prevalent in certain rural communities around the world. It predominantly affects males over their forties. It has many other names such as Bietti's band-shaped nodular dystrophy, Labrador keratopathy, spheroidal degeneration, chronic actinic keratopathy, oil droplet degeneration, elastoid degeneration and keratinoid corneal degeneration. CDK is characterized by the haziness and opalescence of the cornea's most anterior layers which go through three stages with increasing severity. Globular deposits of different sizes may be histopathologically observed under the corneal epithelium by means of light and electron microscopy. The coalescence and increased volume of these spherules may cause the disruption of Bowman's membrane and the elevation and thinning of the corneal epithelium. The exact aetiology and pathogenesis of CDK are unknown, but they are possibly multifactorial. The only treatment in CDK advanced cases is a corneal transplantation, which in different impoverished regions of the world is not an available option. Many years ago, the clinical and histological aspects of this disease were described in several articles. This review highlights new scientific evidence of the expanding knowledge on CDK's pathogenesis which will open the prospect for new therapeutic interventions. [ABSTRACT FROM AUTHOR]

. Purpose: To evaluate the efficacy of keratectomy in treating irregular astigmatism caused by peripheral hypertrophic subepithelial corneal degeneration (PHSD) and to study the possible underlying immunological risk factors. Materials and methods: Patients (14 eyes) with diagnosed PHSD were treated with superficial keratectomy with or without the assistance of phototherapeutic keratectomy (VisX S4; VisX Inc., Santa Ana, CA, USA). Thirteen patients were subjected to analysis of human leucocyte antigen (HLA) genes, complement C4 gene numbers and total plasma immunoglobulin levels. Immunological risk factors between patients and a control group comprising 150 individuals were compared. Results: The mean preoperative best spectacle corrected visual acuity (BCVA) improved from 0.16 ± 0.22 (LogMAR scale range 0-0.7) to 0.06 ± 0.13 (−0.1-0.4) (p < 0.01). The mean preoperative astigmatism decreased significantly from 3.8 ± 2.1 D (range 1.2-8.2) to 2.1 ± 1.4 (range 0.6-5.0, p = 0.02) based on corneal topography. The HLA-B*44 allele and the ancestral haplotype (AH) 8.1 were found significantly more often in PHSD patients than in controls (both p = 0.03). No differences in the C4 genes were found. Conclusions: Astigmatism secondary to PHSD can be effectively treated with keratectomy. Peeling of the fibrotic tissue reduced astigmatism and improved visual performance. We suggest that HLA-B*44 allele and AH 8.1 haplotype are immunological factors predisposing to the development of PHSD. The consequent disruption/alteration of the limbal barrier may lead to corneal peripheral fibrous formation inducing astigmatism. [ABSTRACT FROM AUTHOR]

Intravenous lipid emulsion is a recommended treatment for local anesthetic intoxication. The lipid sink theory hypothesizes that the mechanism behind the lipid treatment is the entrapment of toxic drugs in plasma, preventing them from reaching target receptors. Lipid sink treatment has also been used as a last refuge treatment for severe tricyclic antidepressant intoxication with seemingly beneficial results. We selected three drugs, i.e. amiodarone, ketamine, and amitriptyline, that can cause severe intoxication and compared their interactions with two commercial fat emulsions (Intralipid® and ClinOleic®) and one synthetic liposome (80:20 mol% phosphatidylcholine/phosphatidylglycerol) dispersion. The interaction studies were carried out by capillary electrokinetic chromatography and the retention factors and distributions constants of the drugs were calculated. The results demonstrate that there is stronger interaction between the drugs and the synthetic liposome dispersion than with the commercial emulsions. [ABSTRACT FROM AUTHOR]

Purpose: To report the corneal thinning during and after corneal cross-linking (CXL). Design: Prospective, nonrandomized, single-center observational study. Methods: Thirty patients (30 eyes; 9 female, 21 male; age, 38 ± 12 years) were consecutively scheduled for CXL between January 23 and July 6, 2009. Twenty-four eyes had progressive keratoconus, 2 had pellucid marginal degeneration, 3 eyes had progressive keratectasia after a LASIK operation, and 1 eye had pseudophakic bullous keratopathy. Riboflavin-ultraviolet A (UVA)-induced CXL included the instillation of 0.1% riboflavin drops for 30 minutes followed by riboflavin instillation combined with UVA irradiation for another 30 minutes. Corneal thickness was measured preoperatively, during CXL, and after 1 and 6 months using an ultrasound pachymeter. Changes in the endothelial cell count, corneal steepness, refraction, and visual performance are also given. Results: On average, the corneas thinned 87 ± 40 μm (range, 37-206 μm; 19% ± 7%) during a 60-minute CXL treatment. In 1 patient, the cornea did not swell, even with hypotonic solution such that CXL would be safe. After 1 month, the corneal thickness was lower than the preoperative thickness, but after 6 months, the corneas had regained their original thicknesses. The endothelial cell count and corneal steepness were unchanged after CXL. The UCVA (uncorrected visual acuity) and BSCVA (best spectacle-corrected visual acuity) were improved 6 months after CXL. Conclusions: Corneal thickness decreases significantly during CXL, even to a level where the health of the endothelium and cornea is jeopardized. Visual performance is improved 6 months after CXL. [ABSTRACT FROM AUTHOR]

. Purpose: Climatic droplet keratopathy (CDK) is an acquired corneal disease characterized by progressive scarring of the cornea. In several corneal diseases, matrix metalloproteinases (MMPs) are upregulated during the degradation of epithelial and stromal tissues. We investigated the levels, degree of activation and molecular forms of MMP-2, MMP-9, MMP-8 and MMP-13 and their tissue inhibitors TIMP-1 and TIMP-2 in tear fluid of patients with CDK. Methods: Seventeen CDK patients and 10 controls living in Argentine Patagonia received a complete eye examination, and MMPs and TIMP-1/2 were determined by immunofluorometric assay (IFMA), gelatin zymography and quantitative Western immunoblot analysis in tear samples. Results: The MMPs were detected mostly in their latent forms. The levels of MMP-9 and MMP-2 were found to be significantly elevated in CDK patients, whereas latent and active MMP-8 levels were significantly enhanced in controls. There was no significant difference in the level of MMP-13. TIMPs were found as part of complexes, and the TIMP-1 levels were significantly lower in patients than controls. Conclusion: Elevated MMP-2 and MMP-9 levels have been implicated in the failure of corneal re-epithelialization, and enhanced MMP-2 and MMP-9 levels in CDK patients suggest that these MMPs may play a role in corneal scarring in CDK. Elevated levels of MMP-8 suggest a defensive role for this MMP in inflammatory reactions associated with recurring corneal traumas. Decreased expression of TIMP-1 in CDK patients suggest deficient antiproteolytic shield likely to render the corneas of CDK patients vulnerable to enhanced MMPs. Overall, these data suggest a mechanistic link between MMPs and TIMP-1 level in cornea and tears with corneal scarring in CDK. [ABSTRACT FROM AUTHOR]

RP2 is a ubiquitously expressed protein encoded by a gene associated with X-linked retinitis pigmentosa (XLRP), a retinal degenerative disease that causes severe vision loss. Previous in vitro studies have shown that RP2 binds to ADP ribosylation factor-like 3 (Arl3) and activates its intrinsic GTPase activity, but the function of RP2 in the retina, and in particular photoreceptor cells, remains unclear. To begin to define the role of RP2 in the retina and XLRP, we have conducted biochemical studies to identify proteins in retinal cell extracts that interact with RP2. Here, we show that RP2 interacts with N-ethylmaleimide sensitive factor (NSF) in retinal cells as well as cultured embryonic kidney (HEK293) cells by mass spectrometry-based proteomics and biochemical analysis. This interaction is mediated by the N-terminal domain of NSF. The E138G and Δ1137 mutations of RP2 known to cause XLRP abolished the interaction of RP2 with the N-terminal domain of NSF. Immunofluorescence labeling studies further showed that RP2 colocalized with NSF in photoreceptors and other cells of the retina. Intense punctate staining of RP2 was observed close to the junction between the inner and outer segments beneath the connecting cilium, as well as within the synaptic region of rod and cone photoreceptors. Our studies indicate that RP2, in addition to serving as a regulator of Arl3, interacts with NSF, and this complex may play an important role in membrane protein trafficking in photoreceptors and other cells of the retina. [ABSTRACT FROM AUTHOR]

Abstract: In the case of local anesthetic intoxication, intravenous administration of lipid-based Intralipid dispersion (Fresenius Kabi) can be used for the entrapment of hydrophobic drugs. Our long-term aim is to develop a sensitive, efficient, and non-harmful lipid-based formulation to specifically trap harmful substances. In this study liposome electrokinetic capillary chromatography (LEKC) was used to study the interactions between local anesthetics and Intralipid or liposome dispersions. Intralipid dispersion and extruded liposomes with different concentrations of 1-palmitoyl-2-oleyl-sn-glycerophosphatidylcholine (POPC), phosphatidylglycerol, cardiolipin, cholesterol, oleic acid, and linoleic acid were used as a pseudostationary phase in LEKC and their interactions with lidocaine, prilocaine, and bupivacaine were studied. POPC liposomes containing 1mol% of palmitoyl-2-[12-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]dodecanoyl]-sn-glycero-3-phosphocholine as a fluorescent marker were used for the first time in LEKC connected with laser-induced fluorescent detection in order to calculate the retention factor for anesthetics. [Copyright &y& Elsevier]

The article presents a case study of cowpox with corneal involvement in a 31-year-old atopic woman, who lived in southern Finland and was unvaccinated for smallpox. The microbiological samples taken from the patient's eye revealed neither bacteria nor respiratory viruses. The patient was provided intravenous antimicrobial treatment with meropenem and vancomycin. The patient had Vero cells infected with conjunctival swab.

Purpose: To evaluate the long-term effects of excimer laser treatment for ametropia after surgical treatment of rhegmatogenous retinal detachment (RRD) with scleral buckles. Setting: Helsinki University Eye Hospital, Helsinki, Finland. Methods: Ten patients (10 eyes) who had 1 or more surgeries for RRD followed by refractive surgery for myopia were retrospectively enrolled in this study and were examined after excimer laser refractive surgery. Photorefractive keratectomy (PRK) or laser in situ keratomileusis (LASIK) was performed using a Star S2 excimer laser system (Visx). The best spectacle-corrected visual acuity (BSCVA), refraction, degree of anisometropia, and topographical changes were evaluated before and after the surgeries. Results: All patients were free of asthenopic symptoms after refractive surgery. At the end of the follow-up, a mean of 67 months ± 14 (SD) after refractive surgery, 6 patients were within ±1.0 diopter of the intended correction. Compared with previously reported cohorts of myopic patients, the achieved refraction in patients who previously had a scleral buckling procedure was worse. The postoperative refraction was stable, and corneal topography did not show induced scar formation, keratectasia, or irregular astigmatism. After refractive surgery, the BSCVA improved 1 Snellen line in 3 patients and 2 lines in 1 patient. One patient lost 1 Snellen line and another patient lost 2 lines. Four patients showed no changes. New retinal complications were not observed. Conclusions: In the long-term, PRK and LASIK were safe methods for the treatment of myopia in RRD patients after scleral buckling. The predictability of myopic LASIK/PRK may be worse than generally reported in myopic cohorts. [Copyright &y& Elsevier]

Purpose: Because of the regulatory role of neuropeptide Y (NPY) in angiogenesis, we set out to determine the presence of the leucine 7−proline 7 (Leu7Pro) polymorphism in exudative age-related macular degeneration (AMD) patients and to analyse its implications. Methods: Genotype analysis of the Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY was performed in blood samples from exudative AMD patients ( n = 240) and control subjects ( n = 79). Results: In all, 11% of exudative AMD patients and 14% of control subjects exhibited the NPY signal peptide Leu7Pro polymorphism. There were no statistically significant differences in Leu7Pro polymorphism frequency between the exudative AMD and control cases, as analysed by Fisher's exact two-sided test. Conclusions: Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY is not a risk factor for exudative AMD. [ABSTRACT FROM AUTHOR]

In circulation the phospholipid transfer protein (PLTP) facilitates the transfer of phospholipid-rich surface components from postlipolytic chylomicrons and very low density lipoproteins (VLDL) to HDL and thereby regulates plasma HDL levels. To study the molecular mechanisms involved in PLTP-mediated lipid transfer, we studied the interfacial properties of PLTP using Langmuir phospholipid monolayers and asymmetrical flow field-flow fractionation (AsFlFFF) to follow the transfer of 14C-labeled phospholipids and [35S]PLTP between lipid vesicles and HDL particles. The AsFlFFF method was also used to determine the sizes of spherical and discoidal HDL particles and small unilamellar lipid vesicles. In Langmuir monolayer studies high-activity (HA) and low-activity (LA) forms of PLTP associated with fluid phosphatidylcholine monolayers spread at the air/buffer interphase. Both forms also mediated desorption of [14C]dipalmitoylphosphatidylcholine (DPPC) from the phospholipid monolayer into the buffer phase, even when it contained no physiological acceptor such as HDL. After the addition of HDL3 to the buffer, HA-PLTP caused enhanced lipid transfer to them. The particle diameter of HA-PLTP was and that of HDL3 ~8 nm as determined by AsFlFFF analysis. Using this method, it could be demonstrated that in the presence of HA-PLTP, but not LA-FLIP, [14C]DPPC was transferred from small unilamellar vesicles (SUV) to acceptor HDL3 molecules. Concomitantly, [35S]-HA-PLTP was transferred from the donor to acceptor, and this transfer was not observed for its low-activity counterpart. These observations suggest that HA-PLTP is capable of transferring lipids by a shuttle mechanism and that formation of a ternary complex between PLTP, acceptor, and donor particles is not necessary for phospholipid transfer. [ABSTRACT FROM AUTHOR]

Purpose: Because of the regulatory role of neuropeptide Y (NPY) in angiogenesis, we set out to determine the presence of the leucine 7−proline 7 (Leu7Pro) polymorphism in exudative age-related macular degeneration (AMD) patients and to analyse its implications. Methods: Genotype analysis of the Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY was performed in blood samples from exudative AMD patients ( n = 240) and control subjects ( n = 79). Results: In all, 11% of exudative AMD patients and 14% of control subjects exhibited the NPY signal peptide Leu7Pro polymorphism. There were no statistically significant differences in Leu7Pro polymorphism frequency between the exudative AMD and control cases, as analysed by Fisher's exact two-sided test. Conclusions: Leu7Pro polymorphism in the signal peptide region of the human prepro-NPY is not a risk factor for exudative AMD. [ABSTRACT FROM AUTHOR]

Abstract: Lysobisphosphatidic acid (LBPA) can be regarded to represent a unique derivative of phosphatidylglycerol. This lipid is highly enriched in late endosomes where it can comprise up to 10–15mol% of all lipids and in these membranes, LBPA appears to be segregated into microdomains. We studied the thermotropic behavior of pure dioleoyl-LBPA mono- and bilayers using Langmuir-lipid monolayers, electron microscopy, differential scanning calorimetry (DSC), and fluorescence spectroscopy. LBPA formed metastable, liquid-expanded monolayers at an air/buffer interface, and its compression isotherms lacked any indication for structural phase transitions. Neat LBPA formed multilamellar vesicles with no structural transitions or phase transitions between 10 and 80°C at a pH range of 3.0–7.4. We then proceeded to study mixed LBPA/dipalmitoylphosphatidylcholine (DPPC) bilayers by DSC and fluorescence spectroscopy. Incorporating increasing amounts of LBPA (up to XLBPA (molar fraction)=0.10) decreased the co-operativity of the main transition for DPPC, and a decrease in the main phase transition as well as pretransition temperature of DPPC was observed yet with no effect on the enthalpy of this transition. In keeping with the DSC data for DPPC, 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC)/LBPA mixed bilayers were more fluid, and no evidence for lateral phase segregation was observed. These results were confirmed using fluorescence microscopy of Langmuir-lipid films composed of POPC and LBPA up to XLBPA=0.50 with no evidence for lateral phase separation. As late endosomes are eminently acidic, we examined the effect of lowering pH on lateral organization of mixed PC/LBPA bilayers by DSC and fluorescence spectroscopy. Even at pH 3.0, we find no evidence of LBPA-induced microdomain formation at LBPA contents found in cellular organelles. [Copyright &y& Elsevier]

Objective: To evaluate visual performance after unilateral photorefractive keratectomy (PRK) performed for ≥2.75-diopter (D) myopic anisometropia.Design: Prospective observational case series.Participants: Eleven patients exhibiting ≥2.75-D myopic anisometropia appropriate for PRK.Methods: Photorefractive keratectomy was performed on 11 eyes of 11 patients for myopic anisometropia ranging from –2.75 to –9.00 D. Best spectacle-corrected visual acuity (VA), contrast sensitivity (CS), and pattern visual evoked potentials (pVEPs) were measured preoperatively and at 3 and 6 months.Main outcome measures: Best spectacle-corrected VA; pVEPs; and CS, measured as the area under the CS curve.Results: Best spectacle-corrected VA increased nonsignificantly 6 months after PRK. A tendency towards decreased latency time of pVEPs for both eyes was observed after PRK. A significant increase in CS occurred after PRK in the operated eye at 6 months, but a tendency toward decreased CS appeared in the unoperated eye at 3 months. Preoperative CS levels, however, were reached at 6 months.Conclusions: The adult central visual system is sensitive to visual deprivation caused by anisometropia. Imbalance between eyes may improve visual performance in the more emmetropic eye. Anisometropia appears to reduce visual performance in the more myopic eye, but this can probably be reversed by refractive correction. [Copyright &y& Elsevier]

Purpose: To examine the inflammatory reaction in acute or late-onset post-laser in situ keratomileusis (LASIK) diffuse lamellar keratitis (DLK) associated with an epithelial defect.Setting: Department of Ophthalmology, Helsinki University Central Hospital, Helsinki, Finland.Methods: Six consecutive LASIK patients presented with stage 2 to 3 unilateral DLK 1 to 4 days after formation of an epithelial detachment (intraoperatively or up to 19 months postoperatively). Five corneas of 5 DLK patients, 1 eye twice, were examined by corneal in vivo confocal microscopy 1 to 8 days after the appearance of the epithelial defect. Confocal microscopy of conjunctival venules was performed in 2 of 6 DLK patients to quantify leukocyte rolling and extravasation. Corneas of 5 patients and conjunctival venules of 4 patients who had uneventful LASIK served as controls.Results: Two of the 4 patients examined 0 to 1 day after the onset of DLK presented with small objects, presumably inflammatory cells (diameter 6.0 to 10.0 μm), in the LASIK flap interface. A third patient examined 1 day after the onset of DLK had larger objects (approximately 13.0 μm in diameter) in the interface. Three other cases (1 to 7 days after the onset of DLK) showed changes typical of keratocyte activation and altered extracellular matrix. All cases healed completely following treatment with steroids. Control LASIK subjects showed some keratocyte activation on day 5.Conclusions: Neither uneventful LASIK nor DLK induced an inflammatory reaction displaying leukocyte rolling in conjunctival venules or extravasation into the conjunctival stroma. Diffuse lamellar keratitis related to an epithelial defect does not always lead to the appearance of inflammatory cells in the flap interface. The corneal manifestations of epithelial defect-related DLK may originate from sterile epithelial–stromal or inflammatory cell–stromal cell interactions, leading to alteration of the keratocyte phenotype. [Copyright &y& Elsevier]

Purpose: To study the effect of photorefractive keratectomy (PRK) on the concentration of group IIA phospholipase A2 (GIIAPLA2) in tears.Setting: Departments of Ophthalmology and Pathology, University of Turku, Turku, and Helsinki University Eye Hospital, Helsinki, Finland.Methods: Tear samples were collected from 25 eyes of 23 patients (mean age 32.3 years ± 8.6 [SD]) preoperatively and 2 and 7 days after PRK. The GIIAPLA2 concentration in the tears was measured by time-resolved fluoroimmunoassay.Results: The GIIAPLA2 concentration was significantly lower and the tear fluid flow rate significantly higher 2 days after PRK than preoperatively. At 7 days, the GIIAPLA2 concentration and the tear fluid flow-corrected excretion of GIIAPLA2 were significantly higher than preoperatively and at 2 days. The tear flow rate was also significantly higher than preoperatively.Conclusions: The GIIAPLA2 content in tears decreased 2 days after PRK due to dilution of the GIIAPLA2 content during hypersecretion of reflex tears. Photorefractive keratectomy caused an increase in the tear flow rate, GIIAPLA2 concentration, and tear fluid flow-corrected excretion of GIIAPLA2 in tears 7 days after surgery, enhancing the protection of tears against bacterial infections. [Copyright &y& Elsevier]

We describe four patients who developed corneal erosion after an exposure to a pepper spray containing toxic carriers. Two of these patients were exposed to a pepper gas containing 5% oleoresin capsicum (OC) as an irritant and 92% trichlorethylene or unknown amount of dichloromethane as a carrier. One patient was exposed to a mock (containing 92% trichlorethylene as a carrier) training pepper gas without OC. The fourth patient was exposed to an unidentified Russian pepper gas spray. Two of the patients were examined by in vivo confocal microscopy to demonstrate the depth and quality of the stromal damage. To test the toxicity of the commercial tear spray, it was analyzed and test sprayed on a soft contact lens and into a plastic cup. Visual acuity was measured and the eyes were examined with a slit-lamp up to 5 months. Physical damage to a soft contact lens was visually acquired. All patients showed a long-lasting, deep corneal and conjuctival erosion, which resolved partly with medical therapy during the following weeks/months. Confocal microscopy revealed corneal nerve damage, and keratocyte activation reaching two-thirds of stroma for one patient. The spray caused serious damage to both the soft contact lens and the plastic cup. The safety of the commercially available pepper sprays should be assessed before marketing, and a list of acceptable ingredients created. The sprays should also have instructions on the use of the compound as well as on the first aid measures after the exposure. Solvents known to be toxic should not be used. [Copyright &y& Elsevier]

Sphingomyelinase, SMase (EC 3.1.4.12), was coupled onto amino-derivatized acrylate microspheres and was shown to retain its catalytic activity. The immobilized enzyme allows one to carry out topical enzymatic reaction in a controlled manner. Accordingly, these spheres were held with a micropipet and using micromanipulator brought into contact with a giant liposome membrane composed of phosphatidylcholine and sphingomyelin (SOPC/C16:0-SM, 0.75:0.25, molar ratio), representing the substrate for the immobilized enzyme. The macroscopic consequences of the enzyme reaction were visualized using fluorescence microscopy as well as differential interference contrast microscopy. The surface contact of the giant vesicle and immobilized enzyme causes membrane microdomain formation and domain clustering (capping) in the membrane and subsequent shedding of small vesicles from the membrane into the interior of the giant liposome. The method described represents a novel approach to study enzymatic reactions and allows manipulating giant vesicles as well as cultured cells in a spatially controlled manner. [ABSTRACT FROM AUTHOR]

Sphingomyelinase, SMase (EC 3.1.4.12), was coupled onto amino-derivatized acrylate microspheres and was shown to retain its catalytic activity. The immobilized enzyme allows one to carry out topical enzymatic reaction in a controlled manner. Accordingly, these spheres were held with a micropipet and using micromanipulator brought into contact with a giant liposome membrane composed of phosphatidylcholine and sphingomyelin (SOPC/C16:0-SM, 0.75:0.25, molar ratio), representing the substrate for the immobilized enzyme. The macroscopic consequences of the enzyme reaction were visualized using fluorescence microscopy as well as differential interference contrast microscopy. The surface contact of the giant vesicle and immobilized enzyme causes membrane microdomain formation and domain clustering (capping) in the membrane and subsequent shedding of small vesicles from the membrane into the interior of the giant liposome. The method described represents a novel approach to study enzymatic reactions and allows manipulating giant vesicles as well as cultured cells in a spatially controlled manner. [ABSTRACT FROM AUTHOR]

Atherosclerosis is characterized by the accumulation in the arterial intima of mainly low-density lipoprotein (LDL)-derived lipids, together with apolipoprotein B-100 (apoB-100), the protein moiety of LDL. Recent studies indicate aggregation of LDL within the arterial wall to represent a critical step in the initiation of this disease. Aggregation of LDL has been further proposed to involve ceramide, the levels of which are elevated in atherosclerotic plaques as well as in LDL isolated from these lesions. Biophysical studies have shown ceramide to have a pronounced tendency for self-aggregation, presumably driven by intermolecular hydrogen bonding. Importantly, the segregated ceramide-enriched lipid phases have high melting temperatures and are in a gel state at 37°C. The plasma levels of sphingomyelin, which upon enzymatic hydrolysis by sphingomyelinase (SMase) yields ceramide, have been shown to correlate with the severity of coronary heart disease. The formation of ceramide from sphingomyelin could thus represent a critical step in atherosclerosis. We recently showed that LDL itself possesses SMase activity. Moreover, sequence analogy with bacterial enzymes suggests that this activity may be intrinsic to apoB-100. Possible physiological role of this activity is uncertain, yet could be involved in nonreceptor-mediated endocytotic entry of LDL into cells. Importantly, it also opens a possible mechanistic link between elevated plasma levels of LDL, apoptosis (programmed cell death), and atherosclerosis. [Copyright &y& Elsevier]

We report here the intracellular (pHi) and lysosomal pH in fibroblasts of six forms of neuronal ceroid lipofuscinoses (NCLs). Acid extrusion rate and pHi values were measured by the membrane-permeant acetoxymethyl ester of the indicator dye, 2′,7′-bis(carboxyethyl)-5-(and-6)-carboxy-fluorescein (BCECF) and lysosomal pH by a spectrofluorometric assay utilizing a novel acidotropic probe, Lysosensor yellow/blue. Intracellular pH was normal in all NCLs. Elevated lysosomal pH was detected in all NCL forms except CLN2 and CLN8. Elevated pH most probably disturbs the catalytic activity of lysosomes and is one important factor in explaining accumulation of ceroid and lipofuscin-like autofluorescent lipopigments characteristic of NCLs. Using the novel spectrofluorometric assay introduced in this study provides a fast and repeatable technique to measure intralysosomal pH from cell suspensions. [ABSTRACT FROM AUTHOR]

The interactions of the assembly factor P17 of bacteriophage PRD1 with liposomes were investigated by static light scattering, fluorescence spectroscopy, and differential scanning calorimetry. Our data show that P17 binds to positively charged large unilamellar vesicles composed of the zwitterionic 1-palmitoyl-2-oleoyl-phosphatidylcholine and sphingosine, whereas only a weak interaction is evident for 1-palmitoyl-2-oleoyl-phosphatidylcholine vesicles. P17 does not bind to negatively charged membranes composed of 1-palmitoyl-2-oleoyl-phosphatidylglycerol and 1-palmitoyl-2-oleoyl-phosphatidylcholine. Our differential scanning calorimetry results reveal that P17 slightly perturbs the phase behaviour of neutral phosphatidylcholine and negatively charged multilamellar vesicles. In contrast, the phase transition temperature of positively charged dimyristoylphosphatidylcholine/sphingosine multilamellar vesicles (molar ratio 9 : 1, respectively) is increased by approximately 2.4 °C and the half width of the enthalpy peak broadened from 1.9 to 5.6 °C in the presence of P17 (protein : lipid molar ratio 1 : 47). Moreover, the enthalpy peak is asymmetrical, suggesting that lipid phase separation is induced by P17. Based on the far-UV CD spectra, the α-helicity of P17 increases upon binding to positively charged micelles composed of Triton X-100 and sphingosine. We propose that P17 can interact with positively charged lipid membranes and that this binding induces a structural change on P17 to a more tightly packed and ordered structure. [ABSTRACT FROM AUTHOR]

Presents a study which compares the chemical behaviors of N-palmitoyl-sphingomyelin and their corresponding ceramides, sphingolipids. Physiologic functions of ceramide; Methodology; Results of the study; Discussion.

Detects the specific binding of gelsolin and other actin regulatory proteins to mixed lipid bilayers by fluorescent phosphoinositide. Formation of vesicles and micelles; Fluorescent lipid synthesis; Ability of derivitized inositol lipids to inactivate gelsolin; Comparative binding of intact gelsolin and PtdIns-(4,5)-P[sub 2].

Reports that amyloid beta-peptides (ABP) are centrally involved in pathogenesis of Alzheimer's disease. Correlation of disease severity with extent of ABP accumulation; Composition of ABP found in cerebral amyloid deposits; Variations of C-terminal residues in series of peptides.

Presents a letter to the editor on the relief of migraine following refractive surgery for anisometropia.

Purpose: To describe epidemiology, causes, treatments and outcomes of all ocular injuries in southern Finland among people aged 61 and older. Methods: All new ocular trauma patients, admitted to the Helsinki University Eye Hospital, during 1 year in 2011–2012. The data were from hospital records and prospectively from patient questionnaires. The follow‐up time was 3 months. Results: The incidence for ocular injuries among the elderly was 38/100 000/year. From 118 patients 69% were men. The mean age was 70.9 years old (median 67). The hospitalization rate was 14%. Injury types were minor traumas (48%), contusions (22%), chemical injuries (10%), eyelid wounds (8%), open globe injuries (OGI; 7%) and orbital fractures (5%). The injuries occurred at home (58%), institutions (12%) and in other public places (12%). The main causes of ocular injury were falls (22%), sticks (19%), superficial foreign bodies (18%) and chemicals (12%). All OGI and 88% of contusions needed a lifelong follow‐up. A permanent visual or functional impairment occurred in 15 (13%) patients. Of these 53% were OGI, 40% contusions and 7% chemical injuries. The causes of permanent injuries were falls (seven cases, 47%), work tools, sports equipment, sticks, chemicals and eyeglasses. The incidence for legal blindness was 2.3/100 000. Conclusion: Minor trauma was the most frequent type, and home was the location of the most occurred eye injuries. Falls were the most frequent and serious cause, but behavioural causes were not significant. Preventive measures should be directed towards the main identified causes and risk factors of the eye injuries in the elderly. [ABSTRACT FROM AUTHOR]

Purpose To determine the current population-based epidemiology, treatment, use of resources and outcomes of children's eye injuries in Finland. Methods The study included all new patients, 16 years of age or under, with ocular or orbital traumas taken into care to the Helsinki University Eye Hospital (population base 1.5 million people) in 1 year. The follow-up period was 3 months. Results Two hundred and two children's eye injuries were treated. The eye injury incidence was 5.2-8.3 per 10 000 per year, including all minor and major eye traumas. Eye injury most likely occurred at the junior high school age (13-16 years). Thirty-three percentage of accidents took place at home and 24% at school or in day care. The most common causes were sports equipment (15%), contact with human body (12%) and superficial foreign bodies (11%). Excluding minor injuries, contusion was the most common diagnosis ( n = 60, 30%). Eighty-seven percentage of contusion patients were estimated to need lifelong follow-up due to elevated glaucoma risk. Nine percentage of all patients had a permanent disability. Guns, fireworks, tools and pellet guns were relatively the most dangerous objects. Pellet guns caused 6% of eye injuries, 36% of them causing permanent impairment. The number of outpatient visits was altogether 443, inpatient days were 49, and 60 children had major surgeries. Conclusions Use of protective eyewear would have prevented or diminished eye traumas caused by pellet gun, floorball, most of the firework and in many superficial foreign body. The use of pellet guns and protective eyewear should be more supervised. Fireworks and tools are not suitable toys for children. [ABSTRACT FROM AUTHOR]

Purpose To describe epidemiology, causes, treatments and outcomes of ocular injuries in adults aged 17 to 60 in southern Finland. Methods All new ocular trauma patients admitted to the Helsinki University Eye Hospital ( HUEH), during 1 year in 2011-2012. The data were from hospital records and prospectively from patient questionnaires. The follow-up time was 3 months. Results The incidence for ocular injury was 88/100 000/year. From 831 trauma patients, 80% were men, 34% were work-related injuries, and 11% were assaults. Most of the injuries were minor traumas (54%). Contusions (22.5%) and chemical injuries and burns (13%) were common. Fractures (5%), lid wounds (3%), open globe injuries ( OGI, 2%) and optic nerve injuries (0.5%) were rare. The main causes of ocular injury were superficial foreign bodies (33%), chemicals (13%), body parts (13%) and sports equipment (10%). The most dangerous objects were needles, stones, pellet guns, tools and guns. No patient with OGI used protective eyewear. All OGI and most of contusions needed a lifelong follow-up. Permanent impairment (73 patients, 9%) was caused most often by body parts, sports equipment and work tools. Conclusion A typical ocular trauma patient was a man aged 31-45 with a minor trauma caused by a foreign body at work and a final visual acuity of 20/20. Most common serious injuries were contusion, OGI or fracture at home or at work and were caused by a body part, sport equipment or work tool. Factors causing common and serious eye injuries provide the targets for protective measures. [ABSTRACT FROM AUTHOR]

Purpose: To study the association of the single nucleotide polymorphism (SNP) rs4073 in the interleukin-8 (IL-8) promoter region with the diagnosis and age of onset of exudative age-related macular degeneration (AMD) in association with the known genetic risk factors for AMD and tobacco smoking. Methods: Medical records, smoking history and angiograms or fundus photographs of 301 patients with exudative AMD, 72 patients with dry AMD and 119 control subjects were analysed retrospectively. The associations of IL-8 rs4073 A→T, CFH rs1061170 T→C, ARMS2 rs10490924 G→T and C3 rs2230199 C→G SNPs with the presence of AMD and with the age of onset of exudative AMD were analysed. Results: Younger age of exudative AMD onset was associated with the homozygous AA genotype of IL-8 rs4073 (p = 0.009, Mann-Whitney U-test), CC genotype of CFH rs1061170 (p = 0.016), TT genotype of ARMS2 rs10490924 (p = 0.001) and with current smoking (p = 0.002). The risk alleles C in CFH rs1061170 (p < 0.0001, Pearson chi-square) and T in ARMS2 rs10490924 (p < 0.0001), as well as smoking (p < 0.0001), were more prevalent in AMD patients compared with controls. No association was found between the IL-8 rs4073 genotype and the presence of AMD. Conclusion: Out of the factors associated with the earlier onset of exudative AMD, only the genotype of IL-8 rs4073 did not appear as a risk factor for AMD in general. IL-8 may have a role in accelerating the development of the choroidal neovascularization in exudative AMD. [ABSTRACT FROM AUTHOR]

Thetear film lipid layer (TFLL) is considered to act as an evaporationbarrier and to maintain the tear film intact between blinks. In vitromethods have, however, failed to reproduce this evaporation-retardingeffect. Wax esters (WEs) are a major component of the TFLL. Closeto their bulk melting temperature, WEs have been found to retard theevaporation of water, but the nature of this mechanism has remainedunclear. We studied the interfacial organization of WE films by measuringtheir isochors and isotherms and evaporation-retarding effect, andwe imaged these films by Brewster angle microscopy (BAM). Behenylpalmitoleate (BP) was used as a representative WE because it resemblesthe WEs found in meibum. At low temperatures, BP forms solid monolayercrystals in which the molecules are organized in a bulk-like extendedconformation. Within approximately 3 °C below the bulk meltingtemperature, these solid monolayer domains coexist with a fluid monolayerfilm. At temperatures above the bulk melting temperature, BP formsa completely fluid monolayer in which the molecules are in a hairpinconformation. A fluid hairpin monolayer of BP does not significantlyretard evaporation, whereas a solid monolayer decreases evaporationby >50%. The results provide a molecular-level rationale for theevaporation-retardingproperties of WEs close to their melting temperature. [ABSTRACT FROM AUTHOR]

Highlights: [•] We simulate interactions of pyrene-linked lipids in a lipid membrane. [•] We study the effects of where pyrenes are attached to the chains of their host lipids. [•] Pyrene-induced perturbations are largely similar in all cases in a DOPC environment. [•] Transition to membrane-spanning pyrene dimers is very abrupt. [ABSTRACT FROM AUTHOR]

. Purpose: Angiogenesis in diabetic retinopathy (DR) is a multifactorial process regulated by hypoxia-induced growth factors and inflammatory cytokines. In addition to the angiogenic switch, the proteolytic processing and altered synthesis of the extracellular matrix are critical steps in this disease. This study was performed to evaluate the levels of matrix metalloproteinase-2 and matrix metalloproteinase-9 (MMP-2 and MMP-9), angiopoietin-1 and angiopoietin-2 (Ang-1 and Ang-2), vascular endothelial growth factor (VEGF), erythropoietin (EPO) and transforming growth factor-β1 (totalTGFβ1) in the vitreous of diabetic eyes undergoing vitrectomy compared with control eyes operated because of macular hole or pucker. Methods: Prospective consecutive controlled observational study performed in the unit of vitreoretinal surgery in Finland during the years 2006-2008. Vitreous samples were collected before the start of the conventional 3-ppp vitrectomy. Vitreous MMP-2 and MMP-9, Ang-1 and Ang-2, VEGF, EPO and TGFβ1 concentrations were measured from 69 patients with Type 1 or 2 diabetes and 40 controls. Results: Comparison of eyes with DR with controls revealed that the mean vitreous concentrations of proMMP-2 (p = 0.0015), totalMMP-2 (p = 0.0011), proMMP-9 (p = 0.00001), totalMMP-9 (p < 0.00001), Ang-2 (p < 0.00001), VEGF (p < 0.00001), EPO (p < 0.00001) and totalTGFβ1 (p = 0.000026) were significantly higher in the former group. A multivariate logistic regression analysis suggested intravitreal Ang-2 concentration being the key marker of PDR (p = 0.00025) (OR = 1507.9). Conclusion: The main new finding is that the intravitreal concentrations of Ang-2 correlated significantly with MMP-9, VEGF, EPO and TGFβ1 levels in diabetic eyes undergoing vitrectomy. Thus, these factors could promote retinal angiogenesis synergistically. [ABSTRACT FROM AUTHOR]

. Purpose: To retrospectively evaluate the visual and refractive outcome of visually impaired adults treated with refractive surgery (photorefractive keratectomy or laser-assisted in situ keratomileusis). Methods: We searched a refractive surgery database comprising 1716 mildly visually impaired patients [best spectacle-corrected visual acuity (BSCVA) on a logMAR scale ≤ −0.1 (Snellen ≤ 0.8)] who had undergone either PRK or LASIK ( n = 96). PRK patients who had visits at 5-7, 8-13 and 14-24 months postoperatively were selected. Eleven patients and nine PRK control myopic patients were found (cohort 1). From the same database, 41 visually impaired patients and 54 controls who had a postoperative control at 14-24 months postoperatively were chosen. These patients formed cohort 2. Results: Preoperatively, in cohort 1, the mean BSCVA on a logMAR scale was −0.15 ± 0.13 (Snellen 0.73 ± 0.16) in visually impaired patients and 0.04 ± 0.02 (Snellen 1.11 ± 0.17) in myopic controls. At 14-24 months postoperatively, the mean BSCVA improved to 0.05 ± 0.04 (Snellen 1.13 ± 0.10) in visually impaired patients and 0.05 ± 0.08 (Snellen 1.13 ± 0.21) in control patients. In cohort 2, preoperatively the mean BSCVA on a logMAR scale was −0.15 ± 0.12 (Snellen 0.74 ± 0.14) in visually impaired patients and 0.01 ± 0.03 (Snellen 1.04 ± 0.10) in myopic controls. At 14-24 months postoperatively, the mean BSCVA improved to 0.02 ± 0.07 (Snellen 1.06 ± 0.16) in visually impaired patients and 0.06 ± 0.06 (Snellen 1.15 ± 0.16) in control patients. Conclusion: Refractive surgery improves BSCVA in visually impaired patients, possibly through plastic changes in the visual cortex. Consequently, refractive surgery may be used successfully for the treatment of visually impaired adults to enhance their visual acuity. [ABSTRACT FROM AUTHOR]

Purpose: To compare the long-term results of photorefractive keratectomy (PRK) for low to moderate myopia performed using a broad-beam laser system or a scanning-slit laser system. Setting: Department of Ophthalmology, University of Helsinki, Helsinki, Finland. Design: Case-control study. Methods: This follow-up study comprised eyes with myopia (−1.25 to −7.00 diopters [D]) or myopic astigmatism (astigmatism lower than −2.50 D) corrected by PRK using a broad-beam (Visx) or scanning-slit (Nidek) laser. Follow-up included a visit at 3 months and at more than 8 years. The uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and manifest refraction were recorded. Results: The broad-beam group comprised 27 eyes and the scanning-slit group, 34 eyes. At the last postoperative follow-up, the UDVA was 0.0 or better in 55% of eyes in the broad-beam group and 65% of eyes in the scanning-slit group. The CDVA was 0.0 or better in all eyes in the broad-beam group and 96% of eyes in the scanning-slit group. Regarding predictability, 48% and 73% of the eyes, respectively, were within ±0.50 D of the intended spherical equivalent refraction. There were no statistically significant differences between the 2 laser groups in any preoperative or postoperative parameter. Conclusion: There were no significant differences in UDVA, CDVA, or SE after PRK for low to moderate myopia between the broad-beam laser system and the scanning-slit laser system. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Abstract: Fatal drug overdoses are a cause for concern all over the world. We present here a lipid-based formulation which has a strong affinity for some common illicit street drugs and can be used in vivo as a lipid ‘sink’. In this study, the in vitro interactions of nine lipophilic drugs and three lipid dispersions were determined by electrokinetic capillary chromatography and fluorescence polarization. Two lipid dispersions, zwitterionic 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine (POPC) and an anionic mixture of POPC and 1-palmitoyl-2-oleyl-sn-glycero-3-[phospho-rac-(1-glycerol)] (POPG) were tested and compared with a commercial lipid dispersion Intralipid®, which has been successfully used for resuscitation of patients in cases of anesthetic overdoses. The interactions between dispersions and the drugs were quantified by means of retention factors and distribution constants, which makes the results highly comparable to those obtained from any other formulation of lipids. The results demonstrate a stronger interaction between the drugs and an artificial liposome dispersion than with the commercial Intralipid dispersion. The liposome dispersion composed of POPC and POPG functions as a lipid ‘sink’ for efficient entrapment of various lipophilic drugs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to describe the morphology, corneal topography and sensitivity in individuals with Dystrophia Helsinglandica. This autosomal dominant corneal disease is characterized by recurrent corneal erosive episodes and progressive subepithelial fibrosis not significantly affecting visual acuity. Methods: The corneas of nine affected and nine unaffected individuals were examined using slit-lamp biomicroscopy, in vivo confocal microscopy (IVCM) and videokeratography. Corneal mechanical sensitivity was also measured using a non-contact esthesiometer. Results: Slit-lamp biomicroscopy revealed that the affected individuals represented different stages of corneal changes, from a nearly normal cornea to subepithelial fibrosis of the central cornea. Corneal changes in affected individuals did not significantly decrease the best spectacle-corrected visual acuity. In vivo confocal microscopy detected morphological changes in the epithelium and stroma. Subepithelial opacity formation including altered keratocytes could be found in the anterior stroma in all affected eyes. With the exception of two eyes (one affected and one unaffected), all videokeratographies showed irregular astigmatism. Corneal sensitivity was significantly lower in affected individuals (p = 0.01). Age and corneal sensitivity showed no correlation. Conclusion: The main morphological findings in affected individuals were discrete and progressive subepithelial fibrosis, in the in vivo confocal microscope corresponding to optically dense extracellular matrix and activated keratocytes. Subbasal nerve morphology was changed in the affected family members who also showed a decreased corneal sensitivity. The findings are per se not specific to the disease. The changes probably reflect a healing response to erosive events on the corneal surface influenced by the genotype. [ABSTRACT FROM AUTHOR]

Focuses on the purification and characterization of the assembly factor P17 of the lipid-containing bacteriophage PRD1. Information on assembly factors; Details on the high heat stability of assembly factor P17; Analysis of the structure of the assembly factor.

Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At the air-water interface, the tear film lipid layer (TFLL), a mixture of lipids and proteins, plays a key role in tear surface tension and is important for the physiological hydration of the ocular surface and for ocular homeostasis. Alterations in tear fluid rheology, differences in lipid composition, or downregulation of specific tear proteins are found in most types of ocular surface disease, including dry eye disease (DED). Artificial tears have long been a first line of treatment in DED and aim to replace or supplement tears. More recently, lipid-containing eye drops have been developed to more closely mimic the combination of aqueous and lipid layers of the TFLL. Over the last 2 decades, our understanding of the nature and importance of lipids in the tear film in health and disease has increased substantially. The aim of this article is to provide a brief overview of our current understanding of tear film properties and review the effectiveness of lipid-based products in the treatment of DED. Liposome lid sprays, emulsion eye drops, and other lipid-containing formulations are discussed. [ABSTRACT FROM AUTHOR]

The article discusses a study that examines atopic dermatitis (AD) as risk factor for intrastromal corneal ring segment (ICRS) extrusion. The study included patients treated with ICRS at the Helsinki University Eye Hospital that developed corneal melts necessitating ICRS removal. It suggests that patients with a history of AD/AKC treated with ICRS implantation should be performed by femtosecond laser-assisted system.

Liposomes were used as biomimetic models in capillary electrokinetic chromatography (EKC) for the determination of distribution constants (K D ) of certain local anesthetics and a commonly used preservative. Synthetic liposomes comprised phosphatidylcholine and phosphatidylglycerol phospholipids with and without cholesterol. In addition, ghost liposomes made from red blood cell (RBC) lipid extracts were used as pseudostationary phase to acquire information on how the liposome composition affects the interactions between anesthetics and liposomes. These results were compared with theoretical distribution coefficients at pH 7.4. In addition to 25 °C, the distribution constants were determined at 37 and 42 °C to simulate physiological conditions. Moreover, the usability of five electroosmotic flow markers in liposome (LEKC) and micellar EKC (MEKC) was studied. LEKC was proven to be a convenient and fast technique for obtaining data about the distribution constants of local anesthetics between liposome and aqueous phase. RBC liposomes can be utilized for more representative model of cellular membranes, and the results indicate that the distribution constants of the anesthetics are greatly dependent on the used liposome composition and the amount of cholesterol, while the effect of temperature on the distribution constants is less significant. [ABSTRACT FROM AUTHOR]

Purpose To analyze the outcome of penetrating keratoplasty (PK) to the first eye for corneal amyloidosis in familial amyloidosis, Finnish type (FAF). Design Single-center, retrospective, nonrandomized, interventional, noncomparative case series. Participants Thirty-one eyes of 31 patients with FAF. Intervention All patients with FAF who had their first PK in Helsinki University Eye Hospital between January 1, 1990, and August 1, 2011, were identified and a retrospective analysis of the patient charts was performed. Main Outcome Measures Best spectacle-corrected visual acuity (BCVA), intraoperative and postoperative complications, graft survival, reason for graft failure, and frequency of regrafting. Results The median follow-up period was 32 months (range, 5–114). After 24 months, the median BCVA was 1.15 on a logarithm of the minimum angle of resolution scale (20/280; mean, 1.1; SD, 0.5) in comparison with the preoperative median BCVA of 1.3 (20/400; mean, 1.3; SD, 0.4). At 24 months, 3 of 18 eyes (17%) had a visual acuity of ≥0.5 (20/63) and 13 of 18 grafts (72%) were clear. Rejection occurred in 6 of 31 primary grafts (19%). Graft failure occurred in 16 of 31 eyes and resulted from surface complications in 11 eyes and additionally from rejection in 5 eyes. Seven eyes needed regrafting (twice in 1 eye). Complications were frequent in the early and late postoperative periods. Presence of preoperative corneal or graft neovascularization was an indicator of a high risk of graft failure and poor visual outcome. Conclusions In a minority of FAF patients, PK improves vision. Owing to the high failure risk and guarded visual prognosis after PK, it is important that both the surgeon and the patient have realistic expectations. It may be reasonable to limit PK to cases with bilateral advanced disease. It seems reasonable to optimize ocular surface health and to delay PK. [ABSTRACT FROM AUTHOR]

The toxicity of some promising biomass-dissolving amidinium-, imidazolium-, and phosphonium-based ionic liquids (ILs), toward two different cell lines, human corneal epithelial cells and Escherichia coli bacterial cells, was investigated. In addition, dynamic light scattering (DLS) and ? potential measurements were used to study the effect of the ILs on the size and surface charge of some model liposomes. Capillary electrophoresis (CE) was used for determination of the electrophoretic mobilities of the liposomes and for determination of the critical micelle concentration (cmc) of the ILs. The toxicity of the phosphonium ILs was highly dependent on the longest linear chain of the IL, due to increasing hydrophobicity, with the long-chain phosphonium ILs being toxic while the shorter-chain versions were significantly less toxic or not toxic at all. Amidinium and imidazolium ILs showed no significant effect on the cells, within the concentration range used. Moreover, the more hydrophobic ILs were found to have a major effect on the surface charges and size distributions of the model liposomes, which can lead to disruption of the lipid bilayer. This indicates that the cytotoxicity is at least to some extent dependent on direct interactions between ILs and the biomembrane. [ABSTRACT FROM AUTHOR]

Purpose: To refine the diagnostic criteria for peripheral hypertrophic subepithelial corneal degeneration (PHSD) and characterize its clinical phenotype, histopathology and immunohistochemical features. Methods: Diagnostic criteria were refined on the basis of literature data. Fourteen patients (13 women and one man; median age 52 years, range 33-66) were identified based on these criteria. Keratectomy specimens were evaluated via routine and immunohistochemical stainings. The main outcome measures were symptoms, clinical phenotype, immunological status and histopathologic results. Results: We defined the diagnostic criteria of typical PHSD as elevated circumferential and perilimbal subepithelial fibrosis with focal superficial corneal neovascularization, which were supported by female sex (93%), bilaterality (86%), the centre being in the upper quadrants (81%) and irregular astigmatism of two dioptres or more. The typical symptoms were reduced vision (86%) and the symptoms of ocular surface disease (64%). Light microscopy showed fibrosis with abundant collagen deposition but no inflammation in all patients. An immunohistochemical analysis of nine patients showed uniform staining for vimentin in three distinct types of fibroblasts in variable proportions: keratocytelike cells that were positive for CD34, myofibroblasts that were positive for smooth muscle actin (SMA) and fibroblasts that were negative for CD34 and SMA. Small numbers of CD68-positive macrophages were also found. Conclusions: Peripheral hypertrophic subepithelial degeneration is characteristic of middle-aged women, in whomit is typically a bilateral idiopathic degeneration of the cornea associated with ocular surface disease and reduced vision. The fibrotic lesions probably undergo remodelling, inducing changes in corneal contour. A smouldering low-grade inflammation favouring low TGF-β1 concentrations is postulated as the primary pathological process leading to PHSD. [ABSTRACT FROM AUTHOR]

Purpose: Sphingolipid (SL) research reached a peak in the past years. Yet this positive trend was not evident for eye research as the relative number of studies centered on SLs is decreasing. Our aim is to encourage the inclusion of SL metabolites in studies of ocular pathophysiology by summarizing recent findings and current awareness concerning ceramides in the anterior segment of the eye. Methods: Review of literature relating to ceramides as bioactive lipids and the extent to which their particular nature was investigated in ocular pathophysiology. Results: Ceramides are rare but indispensable lipids that influence cellular responses through their effects on membrane biophysical properties or direct interaction with target proteins. Their biological significance is increased by variability and adaptability as there are tens of enzymes designed to modulate their function. The eye offers a set of unique environments where ceramides or other SLs have not been extensively studied. Not surprisingly, ceramides were associated with apoptosis in the metabolically active tissues, while little is known about its effects on the biophysical properties of the tears or lens lipids. More so, there are still aspects of the ocular homeostasis control where SLs contribution has not been investigated to date (e.g. pathogen aggression). Conclusions: Ceramides and SL metabolism still receive increasing attention and have proven to be a significant metabolite in many research fields (e.g. cancer, stress response and inflammation) and there are yet many questions that they will aid answer. With the present work, we seek to increase awareness of these lipids also in eye research and to highlight their importance as common regulators of various diseases. [ABSTRACT FROM AUTHOR]

Tear fluid lipid layer (TFLL) residing at the air–waterinterface of tears has been recognized to play an important role inthe development of dry eye syndrome. Yet, the composition, structure,and mechanical properties of TFLL are only partly known. Here, wereport results of coarse-grained simulations of a lipid layer comprisingphospholipids, free fatty acids, cholesteryl esters, and triglyceridesat the air–water interface to shed light on the propertiesof TFLL. We consider structural as well as dynamical properties ofthe lipid layer as a function of surface pressure. Simulations revealedthat neutral lipids reside heterogeneously between phospholipids atrelatively low pressures but form a separate hydrophobic phase withincreasing surface pressure, transforming the initial lipid monolayerto a two-layered structure. When the model of TFLL was compared toa one-component phospholipid monolayer system, we found drastic differencesin both structural and dynamical properties that explain the prominentrole of neutral lipids as stabilizers of the TFLL. Based on our results,we suggest that neutral lipids are able to increase the stabilityof the TFLL by modulating its dynamical and structural behavior, whichis important for the proper function of tear film. [ABSTRACT FROM AUTHOR]

. Purpose: To prospectively study the effect of refractive surgery in the primary visual cortex of adult anisometropic and isometropic myopic patients. Methods: Two anisometropic and two isometropic myopic patients were examined with multifocal functional magnetic resonance imaging technique (mffMRI) before refractive surgery and at 3, 6, 9 and 12 months postoperatively. Two controls without refractive surgery were also examined with mffMRI in the beginning and in the end of the study. Anisometropic patients had only their more myopic eye operated to correct the anisometropia. The myopic isometropic patients had their both eyes operated. Results: Operated anisometropic eyes showed 65% reduced amount of active voxels in foveal data at 12 months postoperatively compared with the preoperative situation. In unoperated anisometropic eyes, the corresponding value was 86% and in myopic patients and controls 31% and 1%, respectively. To confirm this finding, the number of activated voxels representing the innermost ring of the stimulus was also calculated, and an exactly similar phenomenon was encountered in the anisometropic patients. Both anisometropic patients improved the best-spectacle-corrected visual acuity in the operated eye after refractive surgery. Conclusion: Our results suggest that plastic changes may take place in the primary visual cortex of anisometropic adult patients after refractive surgery. [ABSTRACT FROM AUTHOR]

Abstract: Intravenous lipid emulsion is recommended as treatment for local anesthetic intoxication based on the hypothesis that the lipophilic drug is entrapped by the lipid phase created in plasma. We compared a 15.6mM 80/20mol% phosphatidyl choline (PC)/phosphatidyl glycerol (PG)-based liposome dispersion with the commercially available Intralipid® emulsion in a pig model of local anesthetic intoxication. Bupivacaine–lipid interactions were studied by electrokinetic capillary chromatography. Multilamellar vesicles were used in the first in vivo experiment series. This series was interrupted when the liposome dispersion was discovered to cause cardiovascular collapse. The toxicity was decreased by an optimized sonication of the 50% diluted liposome dispersion (7.8mM). Twenty anesthetized pigs were then infused with either sonicated PC/PG liposome dispersion or Intralipid®, following infusion of a toxic dose of bupivacaine which decreased the mean arterial pressure by 50% from baseline. Bupivacaine concentrations were quantified in blood samples using liquid chromatography/mass spectrometry. No significant difference in the context-sensitive plasma half-life of bupivacaine was detected (p =0.932). After 30min of lipid infusion, the bupivacaine concentration was 8.2±1.5mg/L in the PC/PG group and 7.8±1.8mg/L in the Intralipid® group, with no difference between groups (p =0.591). No difference in hemodynamic recovery was detected between groups (p >0.05). [Copyright &y& Elsevier]

Abstract: The purpose of this review is to provide insight into the biophysical properties and functions of tear fluid and lung surfactant – two similar fluids covering the epithelium of two distinctive organs. Both fluids form a layer-like structure that essentially comprise of an aqueous layer next to the epithelium and an anterior lipid layer at the air-water interface. The aqueous layers contain soluble proteins and metabolites, and they are responsible for the host defence system and nutrition of the organ. However, many proteins also interact with the lipid layer and are important for the surface-active function of the fluid film. The lipid layer of lung surfactant comprises mainly of phospholipids, especially phosphatidylcholines, and only small amounts of non-polar lipids, mainly cholesterol. In contrast, tear fluid lipid layer comprises of a mixture of polar and non-polar lipids. However, the relative proportion and the spectrum of different polar and non-polar lipids seem to be more extensive in tear fluid than in lung surfactant. The differing lipid compositions generate distinctive lipid layer structures. Despite the structural differences, these lipid layers decrease the surface tension of the air-water interface. The structure of the tear film lipid layer also minimises the evaporation of the tear fluid. In lung surfactant surface activity is crucial for the function of the organ, as the lipid layer prevents the collapse of the lung alveoli during the compression-expansion cycle of breathing. Similarly the tear film experiences a compression-expansion cycle during blinking. The dynamics of this cycle have been studied to a lesser extent and are not as clear as those of lung surfactant. The common structure and properties suggest a similar behaviour under rapid compression–expansion for both fluids. [Copyright &y& Elsevier]