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Meta-analytic Methods for Defining Prescriptive Genetic Biomarkers of Multi-gene Diseases

In most cases of complex diseases, simple genetics do not explain the etiology of disease and multi-genic analyses require patient samples and data that limit the extent to which such tools may be usefully deployed. Although primary open angle glaucoma (POAG) is clearly associated with mutations in such genes as MYOC, ASB10, WDR36, NTF4, and TBK1,  most cases of POAG do not involve these mutations at all. To better understand the genetic underpinnings of POAG, proprietary meta-analytic method have been applied to transform genetic data and the clinical features of this disease into a prescriptive set of genes for POAG.

Novel Clinical Diagnostic for Dry-Eye-Syndrome

Brief description not available

Imaging Method for Improved Placement of MIGS

Minimally invasive glaucoma surgeries (MIGS), despite their favorable safety profile, cannot achieve the same intraocular pressure reduction as tube shunts or trabeculectomy. There is growing interest in targeting MIGS devices near functioning, large-caliber aqueous and episcleral veins, but methods to image these vessels in vivo are lacking. The present invention relates to the method for imaging episcleral vessels noninvasively and quantifying episcleral regional flow variation along the limbal circumference.

Optical-Based Intraocular Pressure Sensor

Glaucoma is a condition in which intraocular pressure (IOP) causes damage to the optic nerve and progressively leads to permanent loss of vision.  The diagnosis and monitoring of glaucoma requires regular measurements of patients’ IOP.  The standard ocular tonometry techniques currently used in a clinical practice provide only a snapshot of the IOP profile and usually with readings taken weeks or months apart.  More recently, there have been implantable sensors under development that enable long term and continuous IOP monitoring.  However, each has drawbacks in one or more of the following concerns: signal readout, size, sensitivity, power consumption, special instrumentation requirement, and/or complex fabrication processes.

Novel Methods to Cultivate Human Limbal Epithelial Stem Cells

UCLA researchers in the Jules Stein Eye Institute have developed novel methods for cultivating stem cells using human feeder cells. This technology enables a more efficient system of producing pure stem cell populations for therapeutic development.

Eyeglasses-Free Display Towards Correcting Visual Aberrations With Computational Light Field Displays

Almost 170 million people in the United States (~55% of the total U.S. population) wear vision correction. Of this population, more than 63 million people (53%) up to age 64 have presbyopic vision. Eyeglasses have been the primary tool to correct such aberrations since the 13th century. In more modern times, contact lenses and refractive surgery have become viable alternatives to wearing eyeglasses. Unfortunately, these approaches require the observer to either use eyewear or undergo surgery, which is often uncomfortable and costly, and can lead to complications, in the case of surgery. To address these challenges, researchers at the University of California, Berkeley, and MIT have developed vision correcting screen technology which involves digitally modifying the content of a display so that the display can be seen in sharp focus by the user without requiring the use of eyeglasses or contact lenses. By leveraging specialized optics in concert with proprietary prefiltering algorithms, the display architecture achieves significantly higher resolution and contrast than prior approaches to vision-correcting image display. The teams have successfully demonstrated light field displays at low cost backed by efficient 4D prefiltering algorithms, producing desirable vision-corrected imagery even for higher-order aberrations that are difficult to be corrected with conventional approaches like eyeglasses.

Accurate and Robust Eye Tracking with a Scanning Laser Ophthalmoscope

The tracking scanning laser ophthalmoscope (TSLO) provides fast and accurate measurements of fixational eye motion with flexible field of views. Currently, this system is the most accurate, fast and functional eye-tracking system used in a standard ophthalmic instrument. At a basic research level, the benefits of accurate eye-tracking are especially useful for delivering stimuli to targeted retinal locations as small as a single cone. In the clinical domain, advances in imaging and tracking technology help render accurate images which can lead to better outcomes in treating eye disease. Scanning laser ophthalmoscopy (SLO) uses both a horizontal and vertical scanner to image a specific region of the retina. Current state of the art tracking SLO systems are only suitable for observing a narrow field of view (FOV < five degrees) and will lose signal with certain types of eye motion. This is problematic for patients suffering from varying retinal or neurological disorders, where unstable fixation hinders accurate eye-tracking and image acquisition. These include retinal diseases of the macula such as: age-related macular degeneration, or neurological disorders such as: Alzheimer's and Parkinson's disease. In cases such as these, it would be desirable to capture a larger field of view whose image quality is sufficient to track the retina for larger and more rapid eye movements. To help address this problem, researchers at the University of California, Berkeley have developed systems, software, and methods for an image-based high-performance TSLO. Early laboratory experimentation results suggest significantly enhanced eye-tracking in terms of: sampling uniformity of eye motion traces, detection of eye rotation, increased frame rate of image capture, expandable/adjustable FOV, stabilization accuracy of 0.66 arcminutes, and tracking accuracy of 0.2 arcminutes or less across all frequencies. The Berkeley system and techniques show promise for observing detailed structural and functional changes in the eye as a result of age and/or disease like never before.

Mobile Visual Performance Profiler (mVP2)

Traditional vision tests are not typically integrated into a single testing device, resulting in medical assistants or clinicians using multiple charts or devices in multiple locations. Test data is recorded on paper or automatically by a device that is not integrated with other devices. Meta-data of tests are usually not available for immediate interpretation and decision-making. Mobile tablets, smart phones, and laptop computer platforms will offer mobility, accessibility, and affordability that are key indicators of quality medicine. They will make it easier to deliver cost-effective care that is comprehensive and coordinated by ensuring its continuity. Current methods are also generally not portable.

Immunogenic Peptides as Vaccines against Herpes Simplex Virus

Immunogenic peptides isolated from HSV seropositive asymptomatic (ASYMP) individuals induce a CD8+ T cell- dependent protective immunity against herpes virus in a mammal.

Glaucoma Blockbuster

Glaucoma is a devastating condition that can lead to loss of sight.  This is estimated to affect nearly 79.6 million people worldwide by the year 2020.  While there are some treatments that help to prevent vision loss, there are no treatments to correct the condition, until now.   Researchers at the University of California, Davis have determined a novel class of compounds that are effective in the treatment of glaucoma. 

Novel method for performing Corneal Implant

Researchers at the University of California, Davis have developed a novel method for inserting an annular cornea implant into a cornea pocked of the human eye. 

Novel Non-Invasive Method for Screening Patients with Traumatic Brain Injury

Researchers at the University of California, Davis have developed a novel non-invasive and quantitative method for screening patients with Traumatic Brain Injury. 

Nanophotonics-Based Implantable Iop-Sensor With Remote Optical Readout

This invention enables the remote automated monitoring of intraocular pressure in patients or animal models to inform glaucoma treatment and the development of new therapeutics for glaucoma.

Superhydrophobic Induced High Numerical Plastic Lenses

The application of novel manufacturing techniques, chemical modifications and alternative materials produces the next generation of lenses. These lenses are inexpensive, contain improved numerical aperture and can be easily manufactured. Overall, these improvements create new applications for miniaturized optical and optical electronic devices.

Human Retinal Stem Cell Production

Retinal degeneration affects millions of people worldwide and currently there is no effective therapy. Leading causes of irreversible blindness include: age-related macular degeneration (AMD), retinitis pigmentosa, glaucoma and retinal vascular diseases, which are characterized by loss of retinal pigmented epithelium (RPE), photoreceptors, retinal ganglion cells (RGCs) and supporting cells in the retina.Using multi-potent retinal stem cells of this invention to replenish damaged retina with desirable cell types represents a promising therapeutic approach. These cells are less likely than pluripotent cells to form tumors and primary retinal progenitor cells from adult retinal or human fetal tissues have limited expansion capacity and differentiation potential or insufficient quantity of fetal retinal progenitors, with possible ethical concerns. Accordingly, there is a medical need for renewable retinal stem cells with a potential to repopulate both RPE and photoreceptors in degenerated retina with little or no risk of forming tumors.

Methods of Culturing Retinal Pigmented Epithelium Cells

Novel methods of producing high-quality RPE cells with very high yields.

Gene Therapy For Usher Syndrome Type 1B

Brief description not available

Lhx2 Conditional Knockout Mouse ("Lhx2 Cko")

The LIM homeobox gene Lhx2 has been studied and found to be necessary for the normal development of the eye, cerebral cortex, and pituitary glands. In addition, it has been investigated for its role in diseases of the cerebral cortex, including schizencephaly, septo-optic dysplasia, and Joubert syndrome. Due to the importance of the Lhx2 gene, researchers have developed knockout mice without the Lhx2 gene. However, drawbacks to conventional “fixed” knockout mice of the Lhx2 gene include embryonic lethality and the inability to perform mosaic analysis of Lhx2 activation. Newer knockout models that address these drawbacks will allow researchers to enhance their studies of the Lhx2 gene. Researchers at the University of California, Irvine have developed a new Lhx2 conditional knockout mouse. This mouse line is unique in that the place and time of the inactivation of the Lhx2 gene can controlled. Also, this mouse line allows researchers to perform mosaic analyses and does not result in embryonic lethality.

An Automated Digital Method for Analysis of Eyelid Position and Contour

Eyelid contour deformities occur in aging and a number of medical conditions such as Graves disease, ptosis, postoperative lid abnormalities, and congenital lid abnormalities. Digital analysis of eyelid position and contour has the potential to objectively characterize the eyelid examination and improve preoperative and postoperative assessment.

MicroRNA Therapeutics for Augmenting Blood Vessel Growth

This invention provides microRNA therapeutics that augment blood vessel growth, which may have application for indications where it is desired to reduce or stimulate angiogenesis. Reducing or inhibiting angiogenesis may be useful for indications such as degenerative eye diseases and cancer. Stimulating blood vessel growth may be useful for treating indications such as cardiovascular, thrombotic or ischemic diseases. Cells lining blood vessels are usually among the least proliferative cell types, but this desired quiescence may be interrupted in response to growth factors during pathological neovascularization manifested in disease states such as macular degeneration and cancer. MicroRNAs are known to be key regulators of angiogenesis and specific miRNAs have been found to be effective toward these indications.

Nanotopographic Biomimetic Membranes

Available for licensing are patent rights in a method of creating nanostructured membranes with topographic features that closely mimic the topographic environment of a variety of basement membranes found in the body. These membranes therefore can provide a means for controlling a number of important cell behaviors.

Combined Blockade of VEGFR-3 and VLA-1 to Improve Transplant Survival

Among all solid organ or tissue transplantations, corneal transplantation is the most successful, with a 2-year survival rate of 90% in patients with inflamed and avascular (low-risk) graft beds. Unfortunately, the rejection rate reaches as high as 50-90% when the grafting is performed on inflamed and highly vascularized (high-risk) corneas. Many patients who are blind as a result of corneal diseases fall in this category after traumatic, inflammatory, infectious, or chemical damage. Such patients are not considered as good candidates for transplantation surgery and have to give up their hope for vision restoration. To address these challenges, investigators at University of California Berkeley have developed a technical strategy using a combined blockade of vascular endothelial growth factor receptor-3 (VEGFR-3) and very late antigen-1 (VLA-1) that markedly improves high-risk corneal transplant transparency and survival. This strategy suppresses lymphatic vessels in grafted corneas. It provides a new and powerful strategy to combat high-risk corneal transplant rejection. The strategy may also be used to treat low-risk transplant rejection and other immune- or lymphatic-related diseases. It can be locally or systemically administered.

Modulation of Ang-2 to Treat Pathologic Lymphangiogenesis

The lymphatic vascular network penetrates most tissues in the body and plays important roles in a broad spectrum of functions, including immune surveillance, fat absorption and interstitial fluid homeostasis. Numerous disorders have been found to be associated with lymphatic dysfunction, such as cancer metastasis, inflammatory and immune diseases, infection, transplant rejection, obesity, hypertension and lymphedema. However, to date, there is still little effective treatment for most lymphatic disorders. The cornea of the eye provides an ideal tissue for lymphatic research due to its unique features of transparency and it is one of the most favorite models for vascular research. Using this tissue, researchers at UC Berkeley (UCB) are working to advance the understanding the mechanisms underlying pathologic lymphatic processes, such as lymphangiogenesis (LG), for the development of new therapeutic strategies. Angiopoietin is part of a family of vascular growth factors responsible for assembling and disassembling the endothelial lining of blood and lymphatic vessels. Angiopoietin-2 (Ang-2) deficiency leads to abnormal lymphatic vessels. UCB researchers are investigating the role of Ang-2 in corneal inflammatory LG in vivo and in lymphatic endothelial cell (LEC) functions in vitro. Using animal models combined with human cell cultures, Berkeley researchers have discovered that Ang-2 is critically involved in pathologic LG processes and its manipulation by anti-Ang-2 treatment inhibits inflammatory LG in vivo and LEC proliferation and capillary tube formation in vitro. These data and deeper understanding by UCB may offer new therapeutic methods, compositions, and kits to help interfere with LG and related diseases, which can occur both inside and outside the eye.

Live Imaging of Corneal Lymphatic Vessels

Lymphatic research is an explosive field of new discovery in recent years. Lymphatic dysfunction has been found in a wide array of disorders which include but are not limited to cancers and tumors, inflammation, infection, autoimmune diseases, dry eye, chemical burn, and tissue or organ transplant rejection, etc. The cornea provides an optimal site for lymphatic research due to its accessible location, transparent nature, and lymphatic-free but inducible features. Because there are no pre-existing vessels to consider in this unique tissue, it is exceptionally straightforward and accurate to assess lymphatic events (from formation to maturation and regression) in the cornea. Since lymphatic vessels are not easily visible as blood vessels, previous studies using the cornea have relied on traditional immunohistochemistry assays with dead tissues. Currently, there are no means of direct and harmless visualization of lymphatic vessels within live cornea. Investigators at University of California at Berkeley have addressed this challenge by developing the first live imaging of corneal lymphatic vessels. Lymphatic specific dye is injected into the subconjunctival space to visualize lymphatic vessels at various stages in the cornea under a fluorescence stereo, confocal, or two-photon microscope. Moreover, lymphatic vessels can be visualized in different colors to produce two, three, and four-dimensional images or live videos at a molecular level. The investigators have demonstrated a proof of principle in live mouse cornea. The technique allows time course tracking of dynamic lymphatic processes within the same tissue or subject over a short or long period of time, and can be ideally used to assess the progression of disease development and the effect of drug treatment. Live imaging of corneal lymphatic vessels allows visualization of lymphatic vessels in their natural morphology, state, and interactions with the local environment. This noninvasive method of live imaging of corneal lymphatic vessels is readily applicable to patient examination and the lymphatic dye of dextran is bio-degradable and harmless to human health.

Nonlinear Optical Photodynamic Therapy of the Cornea for Corneal Disorders, Cancer and Infection

Researchers at the University of California, Irvine have developed a method using nonlinear optical (NLO), femtosecond infrared lasers for the precise depth and area activation of photosensitizers to treat the cornea.

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