Abstract: Editing of VEGFR2 abrogated angiogenesis in two mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroid neovascularization (CNV). Provided are compositions, e.g., Adeno-Associated Virus (AAV) Vectors comprising sequences encoding CRISPR/Cas9 proteins and guide RNA, and methods of use thereof for editing of Vascular endothelial growth factor receptor 2 (VEGFR2) gene to treat ocular disease associated with pathological angiogenesis, e.g., neovascular age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP).

Abstract: The present disclosure relates to optical fiber coupling systems and methods of coupling optical fibers across and with a magnetic field.

Abstract: Methods are described for predicting ancestral sequences for viruses or portions thereof. Also described are predicted ancestral sequences for adeno-associated virus (AAV) capsid polypeptides. The disclosure also provides methods of gene transfer and methods of vaccinating subjects by administering a target antigen operably linked to the AAV capsid polypeptides.

Abstract: This disclosure relates to methods for expanding inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells) and differentiating inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells) to inner ear hair cells (e.g., atonal homolog 1 (Atoh1)+ inner ear hair cells) and the use of the inner hear supporting cells and hair cells, e.g., for identifying candidate therapeutic compounds for the treatment of hearing loss and balance loss. Additionally, the methods described herein can be used in the treatment of a subject having hearing loss and balance loss that would benefit from increased proliferation and differentiation of inner ear supporting cells (e.g., Lgr5+ inner ear supporting cells).

Abstract: Aspects of the disclosure relate to compositions, nucleic acids, vectors, viruses, and methods useful for treating hearing loss and/or blindness, for example, Usher Syndrome type IF. The present disclosure provides isolated nucleic acids, vectors, and rAAV.9.PHP.B comprising a transgene encoding a mini-PCDH15, and methods of treating hearing loss using the same. The present disclosure also provides a gRNA associated with a base editor to correct one or more mutations in PCDH15 for treating hearing loss and/or vision loss.

Abstract: Methods for identifying and optionally treating subjects, e.g., subjects who have Chronic Rhinosinusitis (CRS), based on the detection of elevated levels of soluble P-glycoprotein in nasal secretions. The methods of treatment can include administration of a therapeutically effective amount of a P-glycoprotein inhibitor.

Abstract: Non-invasive methods of detecting hidden hearing loss (cochlear synaptopathy) based on detection of an abnormal ratio of Summating Potential (SP)/Action Potential (AP) (SP/AP) Ratios.

Abstract: Compositions and provided to induce cells of the inner ear to renter the cell cycle and to proliferate. In particular, hair cells are induced to proliferate by administration of a composition which activates the Myc and Notch. Supporting cells are induced to transdifferentiate to hair cells by inhibition of Myc and Notch activity or the activation of Atoh1. Methods of treatment include the intracellular delivery of these molecules to a specific therapeutic target.

Abstract: The technology described in this document can be embodied in systems and computer-implemented methods for determining a score representing an amount of staining of the cornea. The methods include obtaining a digital image of the cornea stained with a tracer material, receiving a selection of a portion of the image, and processing, by a processing device, the selection to exclude areas with one or more artifacts to define an evaluation area. For each of a plurality of pixels within the evaluation area, a plurality of Cartesian color components are determined and a hue value in a polar coordinate based color space is calculated from the components. An amount of staining of the cornea is then determined as a function of the hue value. The methods also include assigning a score to the evaluation area based on the amount of staining calculated for the plurality of pixels.

Abstract: Methods of using a high-dose statin for treatment of AMD in a patient can be used to regress drusen and/or drusenoid pigment epithelial detachments (PEDs), to prevent atrophy of the RPE and/or one or more photoreceptors, to prevent vision loss and/or improve visual acuity, and/or to prevent progression from dry AMD to wet AMD.

Abstract: This invention relates to drug conjugates useful for localized treatment of diseases or disorders of the middle ear and/or inner ear. Methods of treating diseases or disorders of the middle ear and/or inner ear, pharmaceutical compositions comprising the conjugates, and methods of inhibiting a Tropomyosin receptor kinase are also provided.

Abstract: The invention provides methods and polymer compositions for treating retinal detachment and other ocular disorders, where the methods employ polymer compositions that can form a hydrogel in the eye of a subject. The hydrogel is formed by reaction of (i) a nucleo-functional polymer that is a biocompatible polymer containing a plurality of thio-functional groups —R1-SH wherein R1 is an ester-containing linker, such as a thiolated poly(vinyl alcohol) polymer and (ii) an electro-functional polymer that is a biocompatible polymer containing at least one thiol-reactive group, such as a poly(ethylene glycol) polymer containing alpha-beta unsaturated ester groups.

Abstract: The present disclosure provides compositions and methods for treating subjects at risk for or with sensorineural hearing loss. Such compositions and methods include modulating the epigenetic status of the cell, or rate of protein degradation, to increase expression and/or levels of Atoh1 protein.

Abstract: The present application includes methods, systems and computer readable storage devices for determining a color score for at least a portion of a biological tissue. The subject matter of the application is embodied in a method that includes obtaining a digital image of the biological tissue, and receiving a selection of a portion of the image as an evaluation area. The method also includes determining for each of a plurality of pixels within the evaluation area, a plurality of color components that are based on a Cartesian color space, and determining, from the color components, a hue value in a polar coordinate based color space. The method further includes determining a color value based on the hue value for each of the plurality of pixels, and assigning a color score to the evaluation area based on an average of the color values of the plurality of pixels.

Abstract: The present disclosure provides compositions and methods for treating subjects at risk for or with sensorineural hearing loss by modulating the rate of Atoh1 protein degradation to increase levels of Atoh1 protein.

Abstract: In some embodiments, the present invention provides methods for making resorbable ear tubes including the steps of providing a silk fibroin solution, and forming a silk ear tube from the silk fibroin solution, wherein the silk ear tube is less than 2 mm in length and has an outer diameter of less than 1.5 mm, and wherein the silk ear tube is resorbable. In some embodiments, the present invention also provides methods for treating otitis media including the step of introducing a silk ear tube into the ear canal of a subject, wherein the silk ear tube is less than 2 mm in length and has an outer diameter of less than 1.5 mm, and wherein the silk ear tube is resorbed by the subject.

Abstract: Methods for treating hearing loss that include administering an inhibitor, e.g., a small molecule inhibitor, of casein kinase 1, preferably in combination with a treatment that stimulates Atoh1 gene expression, e.g., a gamma-secretase inhibitor, an Atoh1 stimulatory compound, or a GSK-3-beta inhibitor.

Abstract: A drug delivery system (DDS) including a hydrophobic porous scaffold and a hydrogel having a hydrophilic polymer and one or more biologic drugs provides sustained zero-order release of the one or more biologic drugs. Also provided herein are methods of making and using a DDS including a hydrophobic porous scaffold and a hydrogel having a hydrophilic polymer and one or more biologic drugs.

Abstract: Provided herein are materials and methods for efficiently delivering nucleic acids to cochlear and vestibular cells.

Abstract: This invention generally provides compounds, pharmaceutical compositions, and methods for their use, which include methods that result in increased expression in an Atoh1 gene (e.g., Hath1) in a biological cell. More specifically, the invention relates to the treatment of diseases and/or disorders that would benefit from increased Atoh1 expression, e.g., a hearing impairment or imbalance disorder associated with a loss of auditory hair cells, or a disorder associated with abnormal cellular proliferation.