Familial macular degeneration is a clinically and genetically heterogeneous group of disorders characterized by progressive central vision loss. Here we show that an R373C missense mutation in the prominin 1 gene (PROM1) causes 3 forms of autosomal-dominant macular degeneration. In transgenic mice expressing R373C mutant human PROM1, both mutant and endogenous PROM1 were found throughout the layers of the photoreceptors, rather than at the base of the photoreceptor outer segments, where PROM1 is normally localized. Moreover, the outer segment disk membranes were greatly overgrown and misoriented, indicating defective disk morphogenesis. Immunoprecipitation studies showed that PROM1 interacted with protocadherin 21 (PCDH21), a photoreceptor-specific cadherin, and with actin filaments, both of which play critical roles in disk membrane morphogenesis. Collectively, our results identify what we believe to be a novel complex involved in photoreceptor disk morphogenesis and indicate a possible role for PROM1 and PCDH21 in macular degeneration.

Collagen, the major structural component of nearly all mammalian tissues, undergoes extensive proteolytic remodeling during developmental states and a variety of life-threatening diseases such as cancer, myocardial infarction, and fibrosis. While degraded collagen could be an important marker of tissue damage, it is difficult to detect and target using conventional tools. Here, we show that a designed peptide (collagen hybridizing peptide: CHP), which specifically hybridizes to the degraded, unfolded collagen chains, can be used to image degraded collagen and inform tissue remodeling activity in various tissues: labeled with 5-carboxyfluorescein and biotin, CHPs enabled direct localization and quantification of collagen degradation in isolated tissues within pathologic states ranging from osteoarthritis and myocardial infarction to glomerulonephritis and pulmonary fibrosis, as well as in normal tissues during developmental programs associated with embryonic bone formation and skin aging. The results indicate the general correlation between the level of collagen remodeling and the amount of denatured collagen in tissue and show that the CHP probes can be used across species and collagen types, providing a versatile tool for not only pathology and developmental biology research but also histology-based disease diagnosis, staging, and therapeutic screening. This study lays the foundation for further testing CHP as a targeting moiety for theranostic delivery in various animal models.

of data carriers for space-division multiplexing (SDM) beyond traditional wavelength-division multiplexing (WDM) and polarization-division multiplexing (PDM). [3,4] Such high-speed communications, which can reach the speed of Tbit s −1 , are achieved over both free-space and special vortex fiber using OAM beams multiplexing, WDM and PDM together. [5][6][7] High-speed OAM multiplexing communication system, similar to other optical multiplexing communication systems, involves multiplexers and demultiplexers. Traditional OAM multiplexer and demultiplexer consist of OAM generators, such as spatial phase plates (SPPs) or l-forked holograms, and channel combiners, for example, cascaded beam splitters. [3][4][5][6][7][8][9][10][11] The numbers of OAM generators and combiners correspond to the number of channels with independent information uploading by modulators. Therefore, the system becomes complex and less integrated. Several years ago, a method was proposed to solve such complex sequence of holograms and realized multi-OAMs generation and sorting by coordinate transformation. [2] However, this method introduced new challenges. The integration is limited by the distance between two phase plates and the diffraction of light regardless of the thickness of the components used. To make things worse, typical high-speed optical communications, combining not only SDM but also WDM and PDM, require more than one demultiplexer, which further increases the system complexity.In this paper, we report a physical methodology for multiple OAMs multiplexing and demultiplexing by an off-axis designing principle to integrate all the SDM, WDM, and PDM components into one single ultrathin metasurface. With offaxis incidence of beams representing independent information channels, the component can generate independent coaxial vortex beams with different topological charges as a multiplexer. With vortex beams carrying different OAMs, the channels can be separated into fundamental mode beams at the diverse directions as a demultiplexer. Furthermore, the conservations of momentum make this off-axis diffractive component contain dispersion, which demonstrates its great potentials in SDM-WDM system. For the metasurface based on dipole antenna, there are interesting responses to polarization and OAM, which can be used in PDM-WDM system owing to conservations of momentum and angular momentum. Due to these superior properties, designed metasurface demultiplexer has great potential in high integration of SDM, WDM, and Orbital angular momentum (OAM) has recently gained much interest in high-speed optical communication due to its spatial orthogonality. However, complex spatial phase distributions of OAM make the components difficult for nano-photonic integration. In this work, a method to multiplex and demultiplex multiple OAMs, wavelengths, and polarizations channels by a highly integrated off-axis technique on a metasurface is presented. As a multiplexer, beams without OAM can be transferred into coaxial beams carrying different OAM features by d...