Assessment interocular symmetry of peripapillary vessel density in young myopes with optical coherence tomographic angiography.

PURPOSE: The purpose of our study was to evaluate the interocular symmetry and distribution of peripapillary vessel density in young myopic eyes. METHODS: A cross-sectional observational study was designed. A total of 174 eyes of 87 young myopic patients were recruited in this study. According to spherical equivalent (SE), 48 eyes were classified as mild myopia with a mean SE of - 2.12D (SD 0.66D), 66 as moderate myopia with a mean SE of - 4.50D (SD 0.87D), and 60 as high myopia with a mean SE of - 7.39D (SD 1.30D). Optical coherence tomography angiography (OCTA) was used to measure the vessel density. The distribution and interocular symmetry of peripapillary vessel densities were analyzed. RESULTS: The vessel densities in the whole image, peripapillary, superior and inferior sectors were significantly lower in the high myopia group than in the mild or moderate myopia group (All P < 0.001), and the density in the nasal sector was significantly lower in the high myopia group than in the mild group. And most interesting, the vessel densities in the inside disc and temporal sector showed no difference among the three myopic groups (All P > 0.05). By Pearson correlation analysis, the vessel densities in the whole image, peripapillary, superior, inferior and nasal sectors were negatively correlated with axial length (AL) and SE (All P < 0.001), but vessel densities in the inside disc and temporal sector did not show this correlation (All P > 0.05). Interocular symmetry was observed in all the vascular parameters through paired-samples t-tests (All P > 0.05), intraclass correlation coefficient (ICC) and Pearson correlation analysis (All P < 0.001). CONCLUSION: The density of radial peripapillary capillaries decreased in the myopic eye with axial elongation, and optical vascular parameters showed significant interocular symmetry among young myopic eyes.

Effects of diabetes mellitus on biomechanical properties of the rabbit cornea.

To investigate the effects of diabetes on the biomechanical behavior of cornea in alloxan-induced diabetic rabbits. Diabetes mellitus (DM) was induced in 20 rabbits using alloxan, while another 20 age- and weight-matched non-diabetic rabbits served as controls. Eyes were enucleated after 8 weeks of inducing diabetes and the whole cornea was removed with a 3 mm wide scleral ring and tested under inflation conditions with an internal pressure range of 2.0-30.0 mmHg to determine their stress-strain behavior using an inverse analysis process. The blood glucose level (BG), advanced glycosylation end products (AGEs), central corneal thickness (CCT) and intraocular pressure (IOP) increased significantly in the DM group. There were statistically significant correlations between BG and AGEs (r = 0.768, p = 0.00), and between AGEs and CCT variation upon induction of DM (r = 0.594, p = 0.00). The tangent modulus (Et) of the cornea at four stress levels (1-4 kPa, equivalent to approximately IOP of 7.5, 15, 22.5 and 30 mmHg, respectively) was significantly higher in diabetic rabbits than in the control group (p < 0.05). Further, Et at stress of 2 kPa (which corresponded to the average IOP for the control group) was significantly correlated with BG (r = 0.378, p < 0.05), AGEs (r = 0.496, p < 0.05) and CCT variation upon induction of DM (r = 0.439, p < 0.05). IOP, as measured by contact tonometry, was also significantly correlated with both CCT (r = 0.315, p < 0.05) and Et at 2 kPa (r = 0.329, p < 0.05), and even after correcting for the effects of CCT and Et, IOP still significantly increased with both AGEs (r = 0.772, p = 0.00) and BG (r = 0.762, p = 0.00). The cornea of diabetic rabbits showed a significant increase in mechanical stiffness as evidenced by increases in corneal thickness and tangent modulus. The Et increase may be explained by a non-enzymatic cross-linking of collagen fibrils mediated by AGEs due to the high blood glucose levels in diabetes. The study also found significant IOP increases with higher blood glucose level even after controlling the effects of both corneal thickness and tangent modulus.

Evaluation of the relationship of corneal biomechanical metrics with physical intraocular pressure and central corneal thickness in ex vivo rabbit eye globes.

The relationship of corneal biomechanical metrics provided by the Ocular Response Analyzer (ORA) and Corvis ST (CVS) with physical intraocular pressure (IOPp) and central corneal thickness (CCT) was evaluated. Thirty fresh enucleated eyes of 30 rabbits were used in ex vivo whole globe inflation experiments. IOPp was measured with a pressure transducer and increased from 7.5 to 37.5 mmHg in steps of 7.5 mmHg while biomechanical data was acquired using the ORA and CVS. At least 3 examinations were performed at each pressure level, where CCT and twelve biomechanical metrics were recorded and analyzed as a function of IOPp. The biomechanical metrics included corneal hysteresis (CH) and corneal resistance factor (CRF), obtained by the ORA. They also included the applanation times (A1T, A2T), lengths (A1L, A2L) and velocities (A1V, A2V), in addition to the highest concavity time (HCT), peak distance (PD), radius (HR) and deformation amplitude (DA), obtained by the CVS. The variation of CCT and the twelve biomechanical metrics for the 30 rabbit eyes tested across the 5 pressure stages considered (inter-pressure differences) were statistically significant (P = 0.00). IOPp was highly to moderately correlated with most biomechanical metrics, especially CRF, A1T, A1V, A2V, PD and DA, while the relationships with CH, A2T, A1L and HCT were poor. IOP has important influences on most corneal biomechanical metrics provided by CVS and ORA. Two biomechanical metrics A1V and HR were influenced by CCT after correcting for the effect of IOP in most pressure stages, while the correlation with others were weak. Comparisons of research groups based on ORA and CVS with different IOPs and CCTs may lead to possible misinterpretations if both or one of which are not considered in the analysis.

[The research advance of measuring techniques on corneoscleral constitutive parameters].

The occurrence and development of myopia and keratoconus is closely related to the changes of scleral and corneal biomechanical properties. The accurate measurement of biomechanical properties for corneoscleral tissure is very important on diagnosis of eye diseases, improvement of ocular operation, ocular biological parameter measurement and invention of ophthalmic instrument. Corneoscleral tissue, composed of bundles of compact and staggered collagen fiber and extracellular matrix, constitute the outer surface of the eyeball. The inhomogeneous distribution of the diameter, gap and amount of collagen fiber, makes its biomechanical characteristics really complex, characterized by nonlinear, viscoelastic, anisotropic, regional variation and age-related variation and etc. With the development of medical diagnostic technology, the importance of the ocular biomechanical property measurement is increasingly recognized. Nevertheless, measuring technology on ocular biomechanics properties are still not well understood by the majority of ophthalmologists. In order to facilitate the researchers to select a suitable measuring platform and method, the development of international corneoscleral biomechanical propertiy measuring technology was reviewed in this article.

Exploring Corneal Neovascularization: An Integrated Approach Using Transcriptomics and Proteomics in an Alkali Burn Mouse Model.

Purpose: Corneal neovascularization (CNV) impairs corneal transparency and visual acuity. The study aims to deepen our understanding of the molecules involved in CNV induced by alkali burns, facilitate a better grasp of CNV mechanisms, and uncover potential therapeutic targets. Methods: Eighty-four mice were selected for establishing CNV models via alkali burns. On days 3, 7, and 14 after the burns, corneal observations and histological investigations were conducted. An integrated analysis of RNA sequencing (RNA-seq)-based transcriptomics and label-free quantitative proteomics was performed in both normal and burned corneas. Bioinformatics approaches, encompassing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, were applied to discern differentially expressed genes (DEGs) and crucial signaling pathways. Four potentially CNV-related genes were validated using quantitative real-time PCR (qRT-PCR) and Western blot. Results: Significant CNV was observed on the seventh day. Forty-one genes were differentially expressed in neovascularized corneas, with 15 upregulated and 26 downregulated at both mRNA and protein levels. Bioinformatics analysis revealed that these DEGs participated in diverse biological processes, encompassing retinol and retinoic acid metabolism, neutrophil chemotaxis, and actin filament assembly, along with significant enrichment pathways like cytochrome P450, tyrosine, and phenylalanine metabolism. The upregulation of lymphocyte cytosolic protein 1 (LCP1) and cysteine and glycine-rich protein 2 (CSRP2) genes and the downregulation of transglutaminase 2 (TGM2) and transforming growth factor-beta-induced (TGFBI) genes were confirmed. Conclusions: We analyzed gene expression differences in mouse corneas 7 days after alkali burns, finding 41 genes with altered expression. The exact role of these genes in CNV is not fully understood, but exploring angiogenesis-related molecules offers potential for CNV treatment or prevention.

ALKBH5 Regulates Corneal Neovascularization by Mediating FOXM1 M6A Demethylation.

Purpose: This study aims to explore the regulatory role and potential mechanisms of ALKBH5-mediated N6-methyladenosine (m6A) demethylation modification in corneal neovascularization (CNV). Methods: A mouse CNV model was established through corneal alkali burns. Total m6A levels were measured using an m6A RNA methylation quantification kit. The mRNA expression of candidate m6A-related enzymes was quantified by quantitative RT-PCR. Small interfering RNA targeting ALKBH5 was injected subconjunctivally into alkali-burned mice. The CNV area, corneal epithelial thickness, and pathological changes were evaluated. Protein expression was detected by western blot and immunofluorescence. Human umbilical vein endothelial cells (HUVECs) were treated with IL-6. Plasmid transfection knocked down ALKBH5 or overexpressed FOXM1 in IL-6-induced HUVECs. The assays of CCK8, wound healing, and tube formation evaluated the cell proliferation, migration, and tube formation abilities, respectively. The dual-luciferase assay examined the binding between ALKBH5 and FOXM1. Methylated RNA immunoprecipitation-qPCR detected the m6A levels of FOXM1. Results: Significant CNV was observed on the seventh day. Total m6A levels were reduced, and ALKBH5 expression was increased in CNV corneas and IL-6-induced HUVECs. ALKBH5 knockdown alleviated corneal neovascularization and inflammation and countered IL-6-induced promotion of cell proliferation, migration, and tube formation in HUVECs. ALKBH5 depletion increased m6A levels and decreased VEGFA and CD31 expression both in vivo and in vitro. This knockdown in HUVECs elevated m6A levels on FOXM1 mRNA while reducing its mRNA and protein expression. Notably, FOXM1 overexpression can reverse ALKBH5 depletion effects. Conclusions: ALKBH5 modulates FOXM1 m6A demethylation, influencing CNV progression and highlighting its potential as a therapeutic target.

Proteomic profiling of human corneal stroma from long-term contact lens wearers reveals activation of inflammatory responses.

PURPOSE: To investigate the association between proteomic changes and potential pathogenesis in the human cornea with respect to the duration of wearing soft contact lenses (SCLs). METHODS: A total of 96 corneal stroma samples, obtained via small incision lenticule extraction (SMILE), were equally grouped according to the duration of wearing SCL: 0Y, did not wear SCL; 5Y, wore SCL for<5 years; 5-10Y, wore SCL for 5-10 years; O10Y, wore SCL for>10 years. Liquid chromatography-tandem mass spectrometry was used to identify and quantify protein profiles in the corneal stroma. Expression levels of CO1A1, CO4A1, NFKB1, and IL6RB were determined using western blot and immunohistochemistry analysis. RESULTS: This study quantified a total of 5,668 proteins across samples and identified 2,379 differentially expressed proteins (DEPs) with significantly increased abundance in the three SCL-wearing groups compared with that in the non-SCL-wearing group. Compared with those in the 0Y group, the molecular functions of DEPs in the 5Y, 5-10Y, and O10Y groups were mainly related to translation regulator activity, antigen binding, peptidase inhibitor activity, participation in extracellular matrix (ECM) production, complement activation, and inflammatory responses. Pathway enrichment analysis of DEPs showed that the sphingolipid, phosphatidylinositol 3-kinase-protein kinase B, and hypoxia-inducible factor-1 signaling pathways were activated in the human corneal stroma after long-term SCL use. CONCLUSIONS: Inflammation-related proteomic components in human corneal stroma increased after long-term use of SCL and may act as an essential factor in the molecular pathogenesis of corneal stroma damage.

Self-assembly of Aß-based peptide amphiphiles with double hydrophobic chains.

Two peptide-amphiphiles (PAs), 2C(12)-Lys-Aß(12-17) and C(12)-Aß(11-17)-C(12), were constructed with two alkyl chains attached to a key fragment of amyloid ß-peptide (Aß(11-17)) at different positions. The two alkyl chains of 2C(12)-Lys-Aß(12-17) were attached to the same terminus of Aß(12-17), while the two alkyl chains of C(12)-Aß(11-17)-C(12) were separately attached to each terminus of Aß(11-17). The self-assembly behavior of both the PAs in aqueous solutions was studied at 25 °C and at pHs 3.0, 4.5, 8.5, and 11.0, focusing on the effects of the attached positions of hydrophobic chains to Aß(11-17) and the net charge quantity of the Aß(11-17) headgroup. Cryogenic transmission electron microscopy and atomic force microscopy show that 2C(12)-Lys-Aß(12-17) self-assembles into long stable fibrils over the entire pH range, while C(12)-Aß(11-17)-C(12) forms short twisted ribbons and lamellae by adjusting pHs. The above fibrils, ribbons, and lamellae are generated by the lateral association of nanofibrils. Circular dichroism spectroscopy suggests the formation of ß-sheet structure with twist and disorder to different extents in the aggregates of both the PAs. Some of the C(12)-Aß(11-17)-C(12) molecules adopt turn conformation with the weakly charged peptide sequence, and the Fourier transform infrared spectroscopy indicates that the turn content increases with the pH increase. This work provides additional basis for the manipulations of the PA's nanostructures and will lead to the development of tunable nanostructure materials.

Aggregation behavior of a tetrameric cationic surfactant in aqueous solution.

A star-shaped tetrameric quaternary ammonium surfactant PATC, which has four hydrophobic chains and charged hydrophilic headgroups connected by amide-type spacer group, has been synthesized in this work. Surface tension, electrical conductivity, ITC, DLS, and NMR have been used to investigate the relationship between its chemical structure and its aggregation properties. Interestingly, a large size distribution around 75 nm is observed below the critical micelle concentration (cmc) of PATC, and the large size distribution starts to decrease beyond the cmc and finally transfers to a small size distribution. It is proved that the large size premicellar aggregates may display network-like structure, and the size decrease beyond the cmc is the transition of the network-like aggregates to micelles. The possible reason is that intramolecular electrostatic repulsion among the charged headgroups below the cmc leads to a star-shaped molecular configuration, which may form the network-like aggregates through intermolecular hydrophobic interaction between hydrocarbon chains, while the hydrophobic effect becomes strong enough to turn the molecular configuration into pyramid-like shape beyond the cmc, which make the transition of network-like aggregates to micelles available.

Molecular conformation-controlled vesicle/micelle transition of cationic trimeric surfactants in aqueous solution.

Two star-like trimeric cationic surfactants with amide groups in spacers, tri(dodecyldimethylammonioacetoxy)diethyltriamine trichloride (DTAD) and tri(dodecyldimethylammonioacetoxy)tris(2-aminoethyl)amine trichloride (DDAD), have been synthesized, and the aggregation behavior of the surfactants in aqueous solution has been investigated by surface tension, electrical conductivity, isothermal titration microcalorimetry, dynamic light scattering, cryogenic transmission electron microscopy, and NMR techniques. Typically, both the surfactants form vesicles just above critical aggregation concentration (CAC), and then the vesicles transfer to micelles gradually with an increase of the surfactant concentration. It is approved that the conformation of the surfactant molecules changes in this transition process. Just above the CAC, the hydrophobic chains of the surfactant molecules pack more loosely because of the rigid spacer and intramolecular electrostatic repulsion in the three-charged headgroup. With the increase of the surfactant concentration, hydrophobic interaction becomes strong enough to pack the hydrophobic tails tightly and turn the molecular conformation into a pyramid-like shape, thus leading to the vesicle to micelle transition.

Self-assembly of peptide-amphiphile C12-Abeta(11-17) into nanofibrils.

A peptide-amphiphile (C12-Abeta(11-17)) was constructed with a key fragment of amyloid beta-peptide (Abeta(11-17)) attached to dodecanoic acid through an amide bond. The self-assembly behavior of C12-Abeta(11-17) in aqueous solution is studied at 25 degrees C and at pH 3.0 and 10.0. Abeta(11-17) cannot form ordered self-assemblies. But C12-Abeta(11-17) exhibits a very strong ability to form ordered nanofibrils, and the specific fine structure of the nanofibrils can be modulated simply by adjusting the concentration or pH. The critical micelle concentration of C12-Abeta(11-17) was determined as 0.063 and 0.11 mM at pH 3.0 and 10.0, respectively, indicating a stronger assembling ability of C12-Abeta(11-17) at acidic pH. In 0.47 mM C12-Abeta(11-17) solution at pH 3.0, rodlike fibrils with a diameter of approximately 5 nm and varying length of hundreds of nanometers are observed. When the C12-Abeta(11-17) concentration increases to 1.87 mM at pH 3.0, the above rodlike fibrils pack in parallel and form tapelike fibrils through lateral association. In 1.87 mM C12-Abeta(11-17) solution at pH 10.0, twisted fibrils with regular periodicity of approximately 200 nm are formed by the twisting of approximately 20 nm wide and approximately 11 nm thick nanoribbons. The hydrophobic moiety is necessary in fibril formation, whereas the beta-sheet secondary structure of the peptide moiety plays an essential role in the twisting morphology. This work helps to understand the possible mechanism in amyloid fibrillogenesis and provides an approach to inscribe biological signals in self-assemblies with potential application in biomaterial fabrication.

Coacervation of cationic gemini surfactant with weakly charged anionic polyacrylamide.

Coacervation of cationic gemini surfactant hexamethylene-1,6-bis(dodecyldimethylammonium bromide) (C(12)C(6)C(12)Br(2)) with 10% hydrolyzed polyacrylamide (PAM) has been observed and investigated by turbidity titration, isothermal titration calorimetry, dynamic light scattering and microscopy. Without any assistant additive, the coacervation takes place at very low surfactant concentration, and exists in a broad surfactant concentration range. The morphology of the coacervate sponge phase varies in pore size as a function of C(12)C(6)C(12)Br(2) concentration. The polymer/surfactant aggregates grow from soluble complexes with sizes smaller than 20 nm to micrometer during coacervation, and break up into soluble complexes of about 40 nm after coacervate redissolution.

Molecular dynamics simulations of ammonium surfactant monolayers at the heptane/water interface.

Molecular dynamics simulations have been performed on the monolayers of dodecyltrimethylammonium bromide and gemini surfactants 12-S-12 with S=3, 6, and 12 at the n-heptane/water interfaces. The normal density profiles of the interface show that the distributions of surfactants at the liquid/liquid interface are significantly broader than those at air/water interfaces from comparisons with neutron reflection experiments and previous simulations. The spacers of 12-3-12 and 12-6-12 do not migrate much from the interface, while that of 12-12-12 tends to bend into the oil phase. The conformation of the surfactants shows that the spacers are more flexible than the tails. The characteristic angles of the surfactant well depict the geometry of the surfactants at the interface. The connected N+s of 12-3-12 and 12-6-12 have a prominent peak in the radial distribution functions, while those of 12-12-12 have nearly the same peak with those not connected. It is also found by three-dimensional spatial distribution functions that water molecules and bromide ions prefer to be shared between the positively charged methyl or methylene groups.

Special effect of beta-cyclodextrin on the aggregation behavior of mixed cationic/anionic surfactant systems.

Controllable aggregate transitions are achieved in this work by adding due amounts of beta-cyclodextrin (beta-CD) to mixed cationic/anionic surfactant aqueous solutions. In contrast to its "aggregate breaking" effect in single surfactant systems, aggregate growth is observed in nonstoichiometrical mixed cationic/anionic surfactant systems upon addition of beta-CD. The aggregate growth typically undergoes a micellar elongation and a following micelle-to-vesicle transition, which in turn greatly influences the viscosity and absorbance of the solutions. A possible mechanism of this beta-CD-induced aggregate growth is proposed. In mixed cationic/anionic surfactant systems, the surfactants strongly tend to reach electroneutral equilibrium in aggregates. In the present case, added beta-CD is found to greatly facilitate the equilibrium by transferring the "major" component (whose molar fraction>0.5) of a cationic/anionic surfactant mixture from the aggregates to beta-CD cavities. Consequently, the surfactants in the aggregates approach electroneutral mixing, in favor of low-curved aggregates such as vesicles. This work shows that beta-CD provides an additional degree of freedom to control microstructures and macroproperties for the whole class of mixed cationic/anionic surfactant systems.

Micellization-induced conformational change of a chiral proline surfactant.

A proline surfactant including two chiral carbons, sodium N-dodecanoyl-(4R)-hydroxy-L-prolinate (SDHP), has been synthesized, and its micellization behavior in aqueous solution has been investigated by 1H NMR spectroscopy. Two conformational isomers of SDHP, namely, Z and E, are discriminated in the NMR time scale, and critical micelle concentration is derived for each isomer separately. The transformation from E to Z is observed upon micellization, and the amount of Z isomer is approximately three times that of E isomer in the equilibrated system. Moreover, the variation in chemical shifts with the surfactant concentration reveals the shielding effect of the carboxyl group on the syn-side protons of the pyrrolidine ring, which implies that the pyrrolidine rings arrange in a side-to-side manner and lie parallel to the plane of the carboxyl bonds in the neighboring molecules. The difference in the directions of the carbonyl group between Z and E isomers essentially determines their different micellization abilities and molecular arrangements in the micellization process.

Decompaction of cationic gemini surfactant-induced DNA condensates by beta-cyclodextrin or anionic surfactant.

Compaction of DNA by cationic gemini surfactant hexamethylene-1,6-bis-(dodecyldimethylammoniumbromide) (C12C6C12Br2) and the subsequent decompaction of the DNA-C12C6C12Br2 complexes by beta-cyclodextrin (beta-CD) or sodium dodecyl sulfate (SDS) have been studied by using zeta potential and particle size measurements, atomic force microscopy (AFM), isothermal titration microcalorimetry (ITC), and circular dichroism. The results show that C12C6C12Br2 can induce the collapse of DNA into densely packed bead-like structures with smaller size in an all-or-none manner, accompanied by the increase of zeta potential from highly negative values to highly positive values. In the decompaction of the DNA-C12C6C12Br2 complexes, beta-CD and SDS exhibit different behaviors. For beta-CD, the experimental results suggest that it can remove the outlayer hydrophobically bound C12C6C12Br2 molecules from the DNA-C12C6C12Br2 complexes by inclusion interaction, and the excess beta-CD may attach on the complexes by forming inclusion complexes with the hydrocarbon chains of the electrostatically bound C12C6C12Br2 that cannot be removed. The increase of steric hindrance due to the attachment of beta-CD molecules results in the decompaction of the DNA condensates though the true release of DNA cannot be attained. However, for SDS, the experimental results suggest that it can realize the decompaction and release of DNA from its complexes with C12C6C12Br2 due to both ion-pairing and hydrophobic interaction between SDS and C12C6C12Br2.

Clinical Evaluation of Methods to Correct Intraocular Pressure Measurements by the Goldmann Applanation Tonometer, Ocular Response Analyzer, and Corvis ST Tonometer for the Effects of Corneal Stiffness Parameters.

PURPOSE: To evaluate the effectiveness of methods to correct intraocular pressure (IOP) measurements obtained using the Goldmann applanation tonometer (GAT), the ocular response analyzer (ORA), and the Corvis ST tonometer (CVS) for the effects of corneal stiffness parameters: central corneal thickness (CCT), corneal curvature (R), and age in a Chinese population. PATIENTS AND METHODS: Data were collected for 99 eyes of 99 participants. Whereas cornea-corrected IOP was obtained directly from ORA (ORA-IOPcc), cornea correction in GAT and CVS was implemented using multiparameter equations developed earlier. The study also included IOP measurements by the dynamic contour tonometer, which is thought to be less affected by corneal stiffness parameters than other tonometers. Statistical analyses were performed to determine the association of both uncorrected and corrected IOP with the main stiffness parameters: CCT, R, and age. RESULTS: After correction, a significantly decreased association between the GAT (from r=0.15 to r=-0.02), ORA (from r=0.24 to r=-0.19), and CVS (from r=0.47 to r=0.004) IOP measurements and the CCT was found, to levels below that with the dynamic contour tonometer-IOP (r=0.11). The IOP measurements made by the 4 tonometers, both uncorrected and corrected, did not correlate with age. The same was true for R except with ORA-IOPcc (r=0.23). CONCLUSIONS: CCT accounted for the majority of variance in IOP, whereas age and R had a much smaller effect. The IOP correction processes studied were successful in reducing reliance of IOP measurements, especially those by GAT and CVS, on CCT in a healthy Chinese population.

Effect of Misalignment between Successive Corneal Videokeratography Maps on the Repeatability of Topography Data.

PURPOSE: To improve the reliability of corneal topographic data through the development of a method to estimate the magnitude of misalignment between successive corneal videokeratography (VK) maps and eliminate the effect of misalignment on the repeatability of topography data. METHODS: Anterior and posterior topography maps were recorded twice for 124 healthy eyes of 124 participants using a Pentacam, and the repeatability of measurements was assessed by calculating the differences in elevation between each two sets of data. The repeatability of measurements was re-assessed following the determination of the magnitude of misalignment components (translational displacements: x0, y0 and z0, and rotational displacements: α, ß and γ) between each two data sets and using them to modify the second data set within each pair based on an Iterative Closest Point (ICP) algorithm. The method simultaneously considered the anterior and posterior maps taken for the same eye since they were assumed to have the same set of misalignment components. A new parameter, named Combined Misalignment parameter (CM), has been developed to combine the effect of all six misalignment components on topography data and so enable study of the association between misalignment and the data repeatability test results. RESULTS: The repeatability tests resulted in average root mean square (RMS) differences in elevation data of 8.46±2.75 µm before ICP map matching when simultaneously considering anterior and posterior surfaces. With map matching and misalignment correction, the differences decreased to 7.28±2.58 µm (P = 0.00). When applied to only the anterior maps, misalignment correction led to a more pronounced reduction in elevation data differences from 4.58±1.84 µm to 2.97±1.29 µm (P = 0.00). CM was found to be associated with the repeatability error (P = 0.00), with posterior maps being responsible for most of the error due to their relatively lower accuracy compared to anterior maps. CONCLUSIONS: The ICP algorithm can be used to estimate, and effectively correct for, the potential misalignment between successive corneal videokeratography maps.

Modulation of Aß(1-40) peptide fibrillar architectures by Aß-based peptide amphiphiles.

Modulation of the fibrillogenesis of amyloid peptide Aß(1-40) with two Aß-based peptide amphiphiles has been studied. Both peptide amphiphiles contain two alkyl chains but in different positions. The two alkyl chains of 2C12-Aß(11-17) are attached to the same terminus of Aß(11-17), while those of C12-Aß(11-17)-C12 are separately attached to opposite termini of Aß(11-17). Thioflavin T fluorescence spectroscopy shows that all the peptide amphiphiles promote the formation of the cross-ß-sheet structure of Aß(1-40) and the aggregation of Aß(1-40), while 2C12-Aß(11-17) does this more efficiently. The atom force microscopy images indicate that the modulations of these two peptide amphiphiles on the Aß(1-40) aggregation experience two distinct pathways. 2C12-Aß(11-17) leads to amorphous aggregates, whereas C12-Aß(11-17)-C12 generates short rodlike fibrils. However, Fourier transform infrared spectroscopy suggests that the amorphous aggregates and rodlike fibrils display similar secondary structures. This work suggests that the aggregation ability and the aggregate structures of the peptide amphiphiles significantly affect their interactions with Aß(1-40) and lead to different morphologies of the Aß(1-40) aggregates.

Fluorescence correlation spectroscopy to determine the diffusion coefficient of α-synuclein and follow early oligomer formation.

Fluorescence correlation spectroscopy (FCS) can be used to determine the diffusion coefficient of fluorescently labeled α-synuclein. It is a technique based on the use of a confocal microscope. By applying FCS in a combination of short sampling times and repeated measurements, the disappearance of individual α-synuclein molecules (called monomers) and the formation of oligomers can be characterized during the early aggregation process.