Biometry of Anterior Segment of Human Eye on Both Horizontal and Vertical Meridians during Accommodation Imaged with Extended Scan Depth Optical Coherence Tomography

Purpose

To determine the biometry of anterior segment dimensions of the human eye on both horizontal and vertical meridians with extended scan depth optical coherence tomography (OCT) during accommodation.

Methods

Twenty pre-presbyopic volunteers, aged between 24 and 30, were recruited. The ocular anterior segment of each subject was imaged using an extended scan depth OCT under non- and 3.0 diopters (D) of accommodative demands on both horizontal and vertical meridians. All the images were analyzed to yield the following parameters: pupil diameter (PD), anterior chamber depth (ACD), anterior and posterior surface curvatures of the crystalline lens (ASC and PSC) and the lens thickness (LT). Two consecutive measurements were performed to assess the repeatability and reproducibility of this OCT. They were evaluated by calculating the within-subject standard deviation (SD), a paired t-test, intra-class correlation coefficients (ICC) and the coefficient of repeatability/reproducibility (CoR).

Results

There were no significant differences between two consecutive measurements on either horizontal or vertical meridians under both two different accommodative statuses (P>0.05). The ICC for all parameters ranged from 0.775 to 0.998, except for the PSC (0.550) on the horizontal meridian under the non-accommodative status. In addition, the CoR for most of the parameters were excellent (0.004% to 4.89%). In all the parameters, only PD and PSC were found different between the horizontal and vertical meridians under both accommodative statuses (P<0.05). PD, ACD, ASC and PSC under accommodative status were significantly smaller than those under the non-accommodative status, except that the PSC at the vertical meridian did not change. In addition, LT was significantly increased when accommodation.

Conclusion

The extended scan depth OCT successfully measured the dimensions of the anterior eye during accommodation with good repeatability and reproducibility on both horizontal and vertical meridians. The asymmetry of lens posterior surface and oval-shaped pupil were found during accommodation.     

A Novel Method for Measuring Anterior Segment Area of the Eye on Ultrasound Biomicroscopic Images Using Photoshop

Purpose

To describe a novel method for quantitative measurement of area parameters in ocular anterior segment ultrasound biomicroscopy (UBM) images using Photoshop software and to assess its intraobserver and interobserver reproducibility.

Methods

Twenty healthy volunteers with wide angles and twenty patients with narrow or closed angles were consecutively recruited. UBM images were obtained and analyzed using Photoshop software by two physicians with different-level training on two occasions. Borders of anterior segment structures including cornea, iris, lens, and zonules in the UBM image were semi-automatically defined by the Magnetic Lasso Tool in the Photoshop software according to the pixel contrast and modified by the observers. Anterior chamber area (ACA), posterior chamber area (PCA), iris cross-section area (ICA) and angle recess area (ARA) were drawn and measured. The intraobserver and interobserver reproducibilities of the anterior segment area parameters and scleral spur location were assessed by limits of agreement, coefficient of variation (CV), and intraclass correlation coefficient (ICC).

Results

All of the parameters were successfully measured by Photoshop. The intraobserver and interobserver reproducibilities of ACA, PCA, and ICA were good, with no more than 5% CV and more than 0.95 ICC, while the CVs of ARA were within 20%. The intraobserver and interobserver reproducibilities for defining the spur location were more than 0.97 ICCs. Although the operating times for both observers were less than 3 minutes per image, there was significant difference in the measuring time between two observers with different levels of training (p<0.001).

Conclusion

Measurements of ocular anterior segment areas on UBM images by Photoshop showed good intraobserver and interobserver reproducibilties. The methodology was easy to adopt and effective in measuring.     

The frizzled pathway regulates the development of arista laterals.

Background  

The frizzled pathway in Drosophila has been studied intensively for its role in the development of planar polarity in wing hairs, thoracic bristles and ommatidia. Selected cells in the arista (the terminal segment of the antenna) elaborate a lateral projection that shares characteristics with both hairs and bristles.     

Capsid Mutated Adeno-Associated Virus Delivered to the Anterior Chamber Results in Efficient Transduction of Trabecular Meshwork in Mouse and Rat

Background

Adeno associated virus (AAV) is well known for its ability to deliver transgenes to retina and to mediate improvements in animal models and patients with inherited retinal disease. Although the field is less advanced, there is growing interest in AAV’s ability to target cells of the anterior segment. The purpose of our study was to fully articulate a reliable and reproducible method for injecting the anterior chamber (AC) of mice and rats and to investigate the transduction profiles of AAV2- and AAV8-based capsid mutants containing self-complementary (sc) genomes in the anterior segment of the eye.

Methodology/Principle Findings

AC injections were performed in C57BL/6 mice and Sprague Dawley rats. The cornea was punctured anterior of the iridocorneal angle. To seal the puncture site and to prevent reflux an air bubble was created in the AC. scAAVs expressing GFP were injected and transduction was evaluated by immunohistochemistry. Both parent serotype and capsid modifications affected expression. scAAV2- based vectors mediated efficient GFP-signal in the corneal endothelium, ciliary non-pigmented epithelium (NPE), iris and chamber angle including trabecular meshwork, with scAAV2(Y444F) and scAAV2(triple) being the most efficient.

Conclusions/Significance

This is the first study to semi quantitatively evaluate transduction of anterior segment tissues following injection of capsid-mutated AAV vectors. scAAV2- based vectors transduced corneal endothelium, ciliary NPE, iris and trabecular meshwork more effectively than scAAV8-based vectors. Mutagenesis of surface-exposed tyrosine residues greatly enhanced transduction efficiency of scAAV2 in these tissues. The number of Y-F mutations was not directly proportional to transduction efficiency, however, suggesting that proteosomal avoidance alone may not be sufficient. These results are applicable to the development of targeted, gene-based strategies to investigate pathological processes of the anterior segment and may be applied toward the development of gene-based therapies for glaucoma and acquired or inherited corneal anomalies.     

FlyPNS,a database of the <Emphasis Type="Italic">Drosophila</Emphasis> embryonic and larval peripheral nervous system

Background  

The embryonic and larval peripheral nervous system of Drosophila melanogaster is extensively studied as a very powerful model of developmental biology. One main advantage of this system is the ability to study the origin and development of individual sensory cells. However, there remain several discrepancies regarding the organization of sensory organs in each abdominal segment A1-A7.     

Formation of corneal endothelium is essential for anterior segment development - a transgenic mouse model of anterior segment dysgenesis

The anterior segment of the vertebrate eye is constructed by proper spatial development of cells derived from the surface ectoderm, which become corneal epithelium and lens, neuroectoderm (posterior iris and ciliary body) and cranial neural crest (corneal stroma, corneal endothelium and anterior iris). Although coordinated interactions between these different cell types are presumed to be essential for proper spatial positioning and differentiation, the requisite intercellular signals remain undefined. We have generated transgenic mice that express either transforming growth factor (alpha) (TGF(alpha)) or epidermal growth factor (EGF) in the ocular lens using the mouse (alpha)A-crystallin promoter. Expression of either growth factor alters the normal developmental fate of the innermost corneal mesenchymal cells so that these cells often fail to differentiate into corneal endothelial cells. Both sets of transgenic mice subsequently manifest multiple anterior segment defects, including attachment of the iris and lens to the cornea, a reduction in the thickness of the corneal epithelium, corneal opacity, and modest disorganization in the corneal stroma. Our data suggest that formation of a corneal endothelium during early ocular morphogenesis is required to prevent attachment of the lens and iris to the corneal stroma, therefore permitting the normal formation of the anterior segment.     

Activated Ras alters lens and corneal development through induction of distinct downstream targets

Background  

Mammalian Ras genes regulate diverse cellular processes including proliferation and differentiation and are frequently mutated in human cancers. Tumor development in response to Ras activation varies between different tissues and the molecular basis for these variations are poorly understood. The murine lens and cornea have a common embryonic origin and arise from adjacent regions of the surface ectoderm. Activation of the fibroblast growth factor (FGF) signaling pathway induces the corneal epithelial cells to proliferate and the lens epithelial cells to exit the cell cycle. The molecular mechanisms that regulate the differential responses of these two related tissues have not been defined. We have generated transgenic mice that express a constitutively active version of human H-Ras in their lenses and corneas.     

Anterior Segment Optical Coherence Tomography for the Quantitative Evaluation of the Anterior Segment Following Boston Keratoprosthesis

Objective

To quantitatively evaluate the anterior segment using anterior segment optical coherence tomography (AS-OCT) following Boston keratoprosthesis type 1.

Methods

A retrospective study consisted of AS-OCT imaging at a single time point postoperatively in 52 eyes. Main outcomes measures include anatomical and functional anterior chamber depth (ACD), angle (ACA) and peripheral and proximal synechiae.

Results

The mean time point of imaging was 19.3 months postoperatively. Average anatomical and functional ACD was 2.0 and 0.21 mm respectively, and mean ACA ranged from 2.5° to 6.14° in representative meridians. An average of 8.7 clock hours of angle closure was observed in the 25 eyes in which all meridians were imaged. The majority of eyes showed peripheral (86.5%) and proximal (67.3%) synechiae.

Conclusions

AS-OCT is a useful tool for quantitative evaluation of anterior segment and angle after keratoprosthesis, which is otherwise poorly visible. The majority of eyes showed shallow ACD, extensive angle closure and synechiae formation.     

The molecular basis of defective lens development in the Iberian mole

Background  

Fossorial mammals face natural selection pressures that differ from those acting on surface dwelling animals, and these may lead to reduced visual system development. We have studied eye development in a species of true mole, the Iberian mole Talpa occidentalis, and present the molecular basis of abnormal lens development. This is the first embryological developmental study of the eyes of any fossorial mammal at the molecular level.     

Anterior and Posterior Ocular Biometry in Healthy Chinese Subjects: Data Based on AS-OCT and SS-OCT

Background

To measure the anterior and posterior ocular biometric characteristics concurrently and to determine the relationship between the iris and choroid in healthy Chinese subjects.

Methods

A total of 148 subjects (270 eyes) were enrolled in this cross-section study. The anterior and posterior ocular biometric characteristics were measured simultaneously by anterior segment optical coherence tomography (AS-OCT) and swept-source optical coherence tomography (SS-OCT).

Results

Compared with male eyes, female eyes had narrower anterior biometric parameters that presented with smaller anterior segment parameters [including anterior chamber depth (ACD), width (ACW), area (ACA), and volume (ACV); (all p<0.001)], narrower anterior chamber angle parameters [including angle opening distance (AOD750), trabecular–iris space area (TISA750), and angle recess area (ARA); (all p<0.001)], higher iris curvature (ICURV) (p = 0.003), and larger lens vaults (LV) (p = 0.019). These anterior ocular biometric parameters were correlated with increasing age (p<0.01). Iris thickness (IT750) and iris area (IAREA) were associated with age, ACW, and pupil diameter (all p<0.05), while choroidal thickness (CT) was associated with age, gender, and axial length (all p<0.05). Univariate regression analysis showed that greater CT was significantly associated with smaller IAREA (p = 0.026).

Conclusion

Compared with male eyes, female eyes had narrower anterior biometric parameters that correlated with increasing age, which would be helpful in explaining the higher prevalence of angle closure rates in the female gender and in aging people. Increased CT might be associated with smaller iris area; however, this possibility needs to be investigated in future studies before this conclusion is made.     

The Repeatability Assessment of Three-Dimensional Capsule-Intraocular Lens Complex Measurements by Means of High-Speed Swept-Source Optical Coherence Tomography

Purpose

To rebuild the three-dimensional (3-D) model of the anterior segment by high-speed swept-source optical coherence tomography (SSOCT) and evaluate the repeatability of measurement for the parameters of capsule-intraocular lens (C-IOL) complex.

Methods

Twenty-two pseudophakic eyes from 22 patients were enrolled. Three continuous SSOCT measurements were performed in all eyes and the tomograms obtained were used for 3-D reconstruction. The output data were used to evaluate the measurement repeatability. The parameters included postoperative aqueous depth (PAD), the area and diameter of the anterior capsule opening (Area and D), IOL tilt (IOL-T), horizontal, vertical, and space decentration of the IOL, anterior capsule opening, and IOL-anterior capsule opening.

Results

PAD, IOL-T, Area, D, and all decentration measurements showed high repeatability. Repeated measure analysis showed there was no statistically significant difference among the three continuous measurements (all P > .05). Pearson correlation analysis showed high correlation between each pair of them (all r >0.90, P<0.001). ICCs were all more than 0.9 for all parameters. The 95% LoAs of all parameters were narrow for comparison of three measurements, which showed high repeatability for three measurements.

Conclusion

SSOCT is available to be a new method for the 3-D measurement of C-IOL complex after cataract surgery. This method presented high repeatability in measuring the parameters of the C-IOL complex.     

The caudal regeneration blastema is an accumulation of rapidly proliferating stem cells in the flatworm Macrostomum lignano

Background  

Macrostomum lignano is a small free-living flatworm capable of regenerating all body parts posterior of the pharynx and anterior to the brain. We quantified the cellular composition of the caudal-most body region, the tail plate, and investigated regeneration of the tail plate in vivo and in semithin sections labeled with bromodeoxyuridine, a marker for stem cells (neoblasts) in S-phase.     

Biological functions of hCG and hCG-related molecules

Background  

hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary.     

Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254)

Introduction  

Acute trauma involving the anterior cruciate ligament is believed to be a major risk factor for the development of post-traumatic osteoarthritis 10 to 20 years post-injury. In this study, to better understand the early biological changes which occur after acute injury, we investigated synovial fluid and serum biomarkers.     

Characterizing the normal proteome of human ciliary body

Background

The ciliary body is the circumferential muscular tissue located just behind the iris in the anterior chamber of the eye. It plays a pivotal role in the production of aqueous humor, maintenance of the lens zonules and accommodation by changing the shape of the crystalline lens. The ciliary body is the major target of drugs against glaucoma as its inhibition leads to a drop in intraocular pressure. A molecular study of the ciliary body could provide a better understanding about the pathophysiological processes that occur in glaucoma. Thus far, no large-scale proteomic investigation has been reported for the human ciliary body.

Results

In this study, we have carried out an in-depth LC-MS/MS-based proteomic analysis of normal human ciliary body and have identified 2,815 proteins. We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1). We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body. We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis.

Conclusions

More than 95% of the identified proteins have not been previously described in the ciliary body proteome. This is the largest catalogue of proteins reported thus far in the ciliary body that should provide new insights into our understanding of the factors involved in maintaining the secretion of aqueous humor. The identification of these proteins will aid in understanding various eye diseases of the anterior segment such as glaucoma and presbyopia.     

Protective effects of total fraction of avocado/soybean unsaponifiables on the structural changes in experimental dog osteoarthritis: inhibition of nitric oxide synthase and matrix metalloproteinase-13

Introduction  

The aims of this study were, first, to investigate the in vivo effects of treatment with avocado/soybean unsaponifiables on the development of osteoarthritic structural changes in the anterior cruciate ligament dog model and, second, to explore their mode of action.     

Segmental identity and cerebellar granule cell induction in rhombomere 1

Background  

Cerebellar granule cell precursors are specifically generated within the hindbrain segment, rhombomere 1, which is bounded rostrally by the midbrain/hindbrain isthmus and caudally by the boundary of the Hoxa2 expression domain. While graded signals from the isthmus have a demonstrable patterning role within this region, the significance of segmental identity for neuronal specification within rhombomere 1 is unexplored. We examined the response of granule cell precursors to the overexpression of Hoxa2, which normally determines patterns of development specific to the hindbrain. How much does the development of the cerebellum, a midbrain/hindbrain structure, reflect its neuromeric origin as a hindbrain segment?     

Lens regeneration in axolotl: new evidence of developmental plasticity

Background

Among vertebrates lens regeneration is most pronounced in newts, which have the ability to regenerate the entire lens throughout their lives. Regeneration occurs from the dorsal iris by transdifferentiation of the pigment epithelial cells. Interestingly, the ventral iris never contributes to regeneration. Frogs have limited lens regeneration capacity elicited from the cornea during pre-metamorphic stages. The axolotl is another salamander which, like the newt, regenerates its limbs or its tail with the spinal cord, but up until now all reports have shown that it does not regenerate the lens.

Results

Here we present a detailed analysis during different stages of axolotl development, and we show that despite previous beliefs the axolotl does regenerate the lens, however, only during a limited time after hatching. We have found that starting at stage 44 (forelimb bud stage) lens regeneration is possible for nearly two weeks. Regeneration occurs from the iris but, in contrast to the newt, regeneration can be elicited from either the dorsal or the ventral iris and, occasionally, even from both in the same eye. Similar studies in the zebra fish concluded that lens regeneration is not possible.

Conclusions

Regeneration of the lens is possible in the axolotl, but differs from both frogs and newts. Thus the axolotl iris provides a novel and more plastic strategy for lens regeneration.