Elevation of eye pressure can lead to blindness in humans. The trabecular meshwork (TM) tissue, which drains the eye and controls eye pressure, is damaged in glaucoma, thus raising eye pressure. Our recent work identified that endoplasmic reticulum (ER) stress to the TM cells is involved in elevation of eye pressure. Specifically, we discovered that two molecules, ATF4 and CHOP, are involved in this process. In this proposal, we will test whether inhibition of these molecules via a new type of drug known as an integrated stress response inhibitor (ISRIB) that lowers eye pressure in mice and cultured TM cells.
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- Gulab Zode, PhDUniversity of North Texas Health Science Center (Fort Worth, TX)ID:G2017199July 1, 2017 to June 30, 2019GlaucomaStandard$150,000
- Sarah McFarlane, PhDUniversity of Calgary (Canada)
In neovascular age-related macular degeneration (AMD), the sprouting of new blood vessels (angiogenesis/neovascularization) leads to the death of the nerve cells of the retina. Neovascular AMD places a substantial burden on patients and the healthcare system. Current approaches to block new blood vessels from forming are not effective in many patients and they have serious side effects. There’s an urgent need for effective new ways to prevent these faulty new blood vessels from forming, but not affect the health of retinal nerve cells or the normal blood vessels. To address this need, we are developing a genetic animal model where we can rapidly identify novel, safe and effective drugs for the treatment of neovascular AMD.ID:M2017002July 1, 2017 to June 30, 2019Macular DegenerationStandard$123,160
- Karen Duff, PhDColumbia University (New York, NY)
There is currently no cure for Alzheimer’s disease (AD). We have identified a new way to treat the disease which is based on stimulating the brains own “garbage disposal units” to remove the toxic proteins that form clumps in the brain, ultimately leading to memory loss. Using a drug we know can target the garbage disposal system of the brain, we will test the effectiveness of this treatment in a model of AD.ID:A2017393SCo-principal Investigators:Natura Myeku, PhDJuly 1, 2017 to June 30, 2020Alzheimer's DiseaseStandard$300,000
This Alzheimer’s Disease Research Grant is made possible in part by support from Lois and Duane Luallin in Memory of Denver E. Perkins and Edwin H. Luallin.
- Linda Zangwill, PhDUniversity of California, San Diego
Numerous studies have suggested that vascular factors (blood supply) are involved in the development of glaucoma, but it is currently not known whether a reduction in blood supply to the eye is a cause or an effect of the glaucoma disease process. Recent advances in imaging technology have made it possible to visualize and measure the retinal blood supply, as well as assess the deep layers of the optic nerve head, including the lamina cribrosa, during routine eye exams. This prospective clinical research study will investigate whether changes in the retinal blood supply precede or follow other structural and mechanical changes in glaucoma.ID:G2017122Co-principal Investigators:Min Suh Hee, MDJuly 1, 2017 to June 30, 2019GlaucomaStandard$150,000
- Pierre De Rossi, PhDUniversity of Chicago (Chicago, IL)
Genetic studies have recently uncovered several genes that can elevate the risk of developing Alzheimer’s disease (AD), including the BIN1 gene as the second strongest genetic risk factor for late onset AD. My lab has generated a BIN1 transgenic model to mimic the increase of BIN1 protein in the brains of people with AD. My goal is to use this transgenic mouse model to investigate how BIN1 functions as a risk factor in AD. I expect that my proposed research will significantly advance the knowledge about BIN1's function in the physiology of the brain, and reveal how it contributes to AD pathology.ID:A2017366FMentors:Gopal Thinakaran, PhDJuly 1, 2017 to June 30, 2019Alzheimer's DiseasePostdoctoral Fellowship$100,000
- Ephraim F. Trakhtenberg, PhDUniversity of Connecticut Health Center (Farmington, CT)
The biological molecular mechanisms controlling the growth of connections in the central nervous system (CNS) are still poorly understood. The inability of the eye to regenerate such connections to the brain is the key reason why vision is lost from optic nerve damage, which can happen in a disease such as glaucoma, cannot be restored. We propose to identify novel biological regulators of the intrinsic ability of the retinal cells to regrow such connections between the eye and the brain. These studies could lead to the development of therapeutics for restoring simple visual abilities to those who became blind due to angle-closure glaucoma, and possibly other types of glaucoma.ID:G2017204July 1, 2017 to June 30, 2019GlaucomaStandard$150,000
- Derek Welsbie, MD, PhDUniversity of California, San Diego (La Jolla, CA)
Nerve cells called retinal ganglion cells (RGCs) form the connection between the eye and the brain. In glaucoma, these nerve cells die and vision is permanently lost. We have previously shown that a protein called dual leucine zipper kinase (DLK) is critical for the death of these cells. Thus, this proposal seeks to develop a gene therapy vector that might interfere with DLK and prevent RGC death and accompanying vision loss.ID:G2017212Collaborators:Donald J. Zack, MD, PhDJuly 1, 2017 to June 30, 2019GlaucomaStandard$150,000
Recipient of the Dr. Douglas H. Johnson Award
- Matthew Van Hook, PhDTruhlsen Eye Institute, University of Nebraska Medical Center (Omaha, NE)
Glaucoma is a disease often associated with increased intraocular pressure (IOP) that causes blindness when the nerve cells that carry information from the eye to the brain, called retinal ganglion cells (RGCs) die. One particular group of RGCs, called melanopsin RGCs, play a critical role in regulating sleep, mood, and pupil constriction, and it is likely that their function is altered during glaucoma. This project seeks to determine how melanopsin RGC performance and signaling to the brain are altered at early stages of glaucoma, after increases in eye pressure, but before RGCs die. This will help doctors understand some of the earliest signs of glaucoma and may lead to the development of entirely new ways to detect the disease at its earliest stages, and thus prevent blindness.ID:G2017027Collaborators:Shan Fan, MD; Deepta Ghate, MDJuly 1, 2017 to June 30, 2019GlaucomaStandard$150,000
- Fenquan Zhou, PhDJohns Hopkins University (Baltimore, MD)
The proposed study aims to investigate two novel approaches for promoting long distance (ie, eye to brain) optic nerve regeneration. First based on our completed genetic study we will test if pharmacological inhibition of an identified protein via direct eye injection can promote long distance optic nerve regeneration or whether, based on strong preliminary data, manipulation of another novel gene can induce such regeneration. The project will identify a potential translational approach for promoting optic nerve regeneration, and also open a new avenue for identifying novel gene targets that can be manipulated to enhance optic nerve regeneration.ID:G2017037July 1, 2017 to June 30, 2019GlaucomaStandard$150,000
This grant is made possible in part by a bequest from the Timothy Miles Charitable Trust.
- Krishnakumar Kizhatil, PhDThe Jackson Laboratory (Bar Harbor, ME)
Glaucoma is a devastating neurodegenerative disease that causes blindness. Glaucoma results from increased pressure in the eye; however, the mechanistic basis of the pressure increase is largely undetermined. Neurons innervating the eye play a role in controlling pressure, but again the specific mechanisms are not clear. We will determine the mechanistic basis of neuronal control of eye pressure using mice and modern imaging and molecular methods.ID:G2017152Collaborators:Simon W. M. John, PhDJuly 1, 2017 to June 30, 2019GlaucomaStandard$150,000