Conditional deletion of β1-integrin from the developing lens leads to loss of the lens epithelial phenotype

Abstractβ1-integrins are cell surface receptors that participate in sensing the cell's external environment. We used the Cre-lox system to delete β1-integrin in all lens cells as the lens vesicle transitions into the lens. Adult mice lacking β1-integrin in the lens are microphthalmic due to apoptosis of the lens epithelium and neonatal disintegration of the lens fibers. The first morphological alterations in β1-integrin null lenses are seen at 16.5 dpc when the epithelium becomes disorganized and begins to upregulate the fiber cell markers β- and γ-crystallins, the transcription factors cMaf and Prox1 and downregulate Pax6 levels demonstrating that β1-integrin is essential to maintain the lens epithelial phenotype. Furthermore, β1-integrin null lens epithelial cells upregulate the expression of α-smooth muscle actin and nuclear Smad4 and downregulate Smad6 suggesting that β1-integrin may brake TGFβ family signaling leading to epithelial–mesenchymal transitions in the lens. In contrast, β1-integrin null lens epithelial cells show increased E-cadherin immunoreactivity which supports the proposed role of β1-integrins in mediating complete EMT in response to TGFβ family members. Thus, β1-integrin is required to maintain the lens epithelial phenotype and block inappropriate activation of some aspects of the lens fiber cell differentiation program

Diverse Roles of Eph/ephrin Signaling in the Mouse Lens

Recent genetic studies show that the Eph/ephrin bidirectional signaling pathway is associated with both congenital and age-related cataracts in mice and humans. We have investigated the molecular mechanisms of cataractogenesis and the roles of ephrin-A5 and EphA2 in the lens. Ephrin-A5 knockout (-/-) mice often display anterior polar cataracts while EphA2(-/-) lenses show very mild cortical or nuclear cataracts at weaning age. The anterior polar cataract of ephrin-A5(-/-) lenses is correlated with multilayers of aberrant cells that express alpha smooth muscle actin, a marker for mesenchymal cells. Only select fiber cells are altered in ephrin-A5(-/-) lenses. Moreover, the disruption of membrane-associated β-catenin and E-cadherin junctions is observed in ephrin-A5(-/-) lens central epithelial cells. In contrast, EphA2(-/-) lenses display normal monolayer epithelium while disorganization is apparent in all lens fiber cells. Immunostaining of ephrin-A5 proteins, highly expressed in lens epithelial cells, were not colocalized with EphA2 proteins, mainly expressed in lens fiber cells. Besides the previously reported function of ephrin-A5 in lens fiber cells, this work suggests that ephrin-A5 regulates β-catenin signaling and E-cadherin to prevent lens anterior epithelial cells from undergoing the epithelial-to-mesenchymal transition while EphA2 is essential for controlling the organization of lens fiber cells through an unknown mechanism. Ephrin-A5 and EphA2 likely interacting with other members of Eph/ephrin family to play diverse functions in lens epithelial cells and/or fiber cells

Tropomodulin1 is required for membrane skeleton organization and hexagonal geometry of fiber cells in the mouse lens

The spectrin–actin network is disrupted in Tmod1 mutants, disturbing fiber cell morphology, and disordering lens cell organization

Inherited Eye Diseases with Retinal Manifestations through the Eyes of Homeobox Genes

Retinal development is under the coordinated control of overlapping networks of signaling pathways and transcription factors. The paper was conceived as a review of the data and ideas that have been formed to date on homeobox genes mutations that lead to the disruption of eye organogenesis and result in inherited eye/retinal diseases. Many of these diseases are part of the same clinical spectrum and have high genetic heterogeneity with already identified associated genes. We summarize the known key regulators of eye development, with a focus on the homeobox genes associated with monogenic eye diseases showing retinal manifestations. Recent advances in the field of genetics and high-throughput next-generation sequencing technologies, including single-cell transcriptome analysis have allowed for deepening of knowledge of the genetic basis of inherited retinal diseases (IRDs), as well as improve their diagnostics. We highlight some promising avenues of research involving molecular-genetic and cell-technology approaches that can be effective for IRDs therapy. The most promising neuroprotective strategies are aimed at mobilizing the endogenous cellular reserve of the retina

The CdZnTe Detector with Slit Collimator for Measure Distribution of the Specific Activity Radionuclide in the Ground

From 2011 in the NRC "Kurchatov Institute" carry out the dismantling of the MR multiloop research reactor. Now the reactor and all technological equipment in the premises of the reactor were dismantled. Now the measurements of radioactive contamination in the reactor premises are made. The most contaminated parts of premises - floor and the ground beneath it. To measure the distribution of specific activity in the ground the CdZnTe detector (volume 500MM3) was used. Detector placed in a lead shielding with a slit collimation hole. The upper part of shielding is made movable to close and open the slit of the collimator. At each point two measurements carried out: with open and closed collimator. The software for determination specific activity of radionuclides in ground was developed. The mathematical model of spectrometric system based on the Monte-Carlo method. Measurements of specific activity of ground were made. Using the results of measurements the thickness of the removed layer of ground and the amount of radioactive waste were calculated

Foveolar muller cells of the pied flycatcher: morphology and distribution of intermediate filaments regarding cell transparency

Specialized intermediate filaments (IFs) have critical importance for the clearness and uncommon transparency of vertebrate lens fiber cells, although the physical mechanisms involved are poorly understood. Recently, an unusual low-scattering light transport was also described in retinal Muller cells. Exploring the function of IFs in Muller cells, we have studied the morphology and distribution pattern of IFs and other cytoskeletal filaments inside the Muller cell main processes in the foveolar part of the avian (pied flycatcher) retina. We found that some IFs surrounded by globular nanoparticles (that we suggest are crystallines) are present in almost every part of the Muller cells that span the retina, including the microvilli. Unlike IFs implicated in the mechanical architecture of the cell, these IFs are not connected to any specific cellular membranes. Instead, they are organized into bundles, passing inside the cell from the endfeet to the photoreceptor, following the geometry of the processes, and repeatedly circumventing numerous obstacles. We believe that the presently reported data effectively confirm that the model of nanooptical channels built of the IFs may provide a viable explanation of Muller cell transparency