The National Eye Institute (NEI) awarded a $615,979 Project Grant under the Vision Research program (CFDA 93.867) to Wayne State University to investigate a promising peptide-based combination therapy that targets hyperglycemia-responsive circuits in the cornea to prevent and treat diabetes-induced corneal complications. The 4-year project aims to: 1) establish the therapeutic role of Thymosin beta 4 (TB4) and Vasoactive Intestinal Peptide (VIP) as a combination treatment against diabetic...
The National Eye Institute (NEI) awarded a $2,270,408 Project Grant (CFDA 93.867 - Vision Research) to Wake Forest University Health Sciences to develop an intravitreal (IVT) delivery system for rexinoid compounds UAB126 and UAB30 as a novel therapy for diabetic retinopathy. The research aims to determine the physiological effects, cellular mechanisms, and molecular pathways by which these rexinoid compounds can prevent and reverse diabetic retinopathy when delivered directly to the retina....
The National Eye Institute (NEI) awarded Vanderbilt University Medical Center a $2,305,702 Project Grant (CFDA 93.867 - Vision Research) to conduct an integrative multi-omics study to discover molecular pathways associated with diabetic retinopathy (DR). The 5-year project aims to: 1) quantify differential transcript and metabolite abundance between participants with type 2 diabetes with and without DR in the Cameron County Hispanic Cohort and replicate findings in the Hispanic Community...
The University of Southern California (USC) received a $480,140 Project Grant from the National Eye Institute (NEI) under the Vision Research program (CFDA 93.867) to develop new treatment strategies for diabetic retinopathy (DR). The key objectives are to: 1) evaluate the targeted delivery of therapeutic extracellular vesicles (exosomes) to areas of retinal vascular dysfunction in DR, and 2) determine if Müller glia-derived exosomes can protect the retinal neurovascular unit and mitigate DR...
This Project Grant award from the National Eye Institute (NEI) under the Vision Research federal grant program (CFDA 93.867) provides $933,533 to Revopsis Therapeutics, Inc. to conduct Investigational New Drug (IND)-enabling preclinical studies for their RO-104 trispecific surrobody therapy. RO-104 targets vascular endothelial growth factor-A (VEGF-A), VEGF-C, and angiopoietin-2 to treat retinal diseases like age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion. The...
This $436,695 Project Grant award from the National Eye Institute (NEI), under the Vision Research program (CFDA 93.867), is supporting the development and evaluation of a novel topical eye drop formulation to deliver HIF-1 inhibitors for treating retinal and choroidal vascular diseases. The primary objectives are to: 1) develop and characterize new polymer-based gelling eye drop formulations to maximize intraocular penetration and drug delivery to the posterior segment, 2) test the maximum...
The National Eye Institute (NEI) has awarded a $144,362 Project Grant under the Vision Research federal grant program (CFDA 93.867) to the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. The award, effective September 1, 2024 through February 28, 2027, will support research to investigate the role of hyperglycemia and hyperinsulinemia in the breakdown of the blood-retinal barrier, which is a leading cause of diabetic retinopathy and preventable blindness. The...
This $131,281 Project Grant was awarded by the National Eye Institute (NEI) under the Vision Research federal grant program (CFDA 93.867). The grant will support research at Northwestern University to investigate the role of myeloid cell transmigration in the progression of non-proliferative diabetic retinopathy (DR). The key objectives are to determine whether and when blocking myeloid cell infiltration can halt DR inflammation, and if blocking leukocyte-endothelial interactions early in the...
The National Eye Institute (NEI) awarded Oakland University a 2-year, $184,117 Project Grant (CFDA 93.867 Vision Research) to investigate the role of G-Coupled Protein Receptors 31 and 39 (GPR31/GPR39) in the pathogenesis of diabetic retinopathy. The researchers will determine the affinities and specificities of GPR31 and GPR39 for the 12/15-lipoxygenase metabolites 12-HETE and 15-HETE, and examine the effects of GPR31/GPR39 gain-loss-of-function on retinal endothelial cells and Müller cells...
This $403,750 Project Grant from the National Eye Institute of the Department of Health and Human Services will fund research into the regulation of retinal microvascular stiffness by the matricellular protein CCN1 and its implications for ischemic retinopathy. The awardee, the Research Foundation for the State University of New York on behalf of SUNY Downstate Health Sciences University, will investigate the effects of CCN1 on the mechanical properties of retinal microvascular endothelial cells...
EVALUATION OF A CONNEXIN-BASED PEPTIDE FOR THE TREATMENT OF DIABETIC RETINOPATHY - DIABETIC RETINOPATHY (DR) IS THE LEADING CAUSE OF BLINDNESS AND VISUAL IMPAIRMENT IN US ADULTS. THE CURRENT STANDARD OF CARE FOR DR IS INTRAVITREAL (IVT) INJECTION OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) THERAPEUTICS TO INHIBIT VASCULAR PERMEABILITY AND NEOVASCULARIZATION. HOWEVER, ANTI-VEGF DRUGS HAVE LIMITED EFFICACY IN A SUBSTANTIAL PERCENTAGE OF DR PATIENTS. THE INVASIVENESS OF IVT INJECTIONS ALSO CORRELATES WITH POOR COMPLIANCE AS WELL AS SERIOUS SIDE EFFECTS. AS SUCH, THERE IS AN UNMET MEDICAL NEED FOR AN INNOVATIVE NONINVASIVE TREATMENT THAT EFFECTIVELY MITIGATES DR PATHOGENESIS AND PROGRESSION. IN THIS RESEARCH APPLICATION, WE PROPOSE TO EVALUATE THE THERAPEUTIC POTENTIAL OF A PEPTIDE-CONTAINING EYE DROP FORMULATION (INEXIN) TO MITIGATE DR PATHOPHYSIOLOGY BY PRESERVING BLOOD-RETINA BARRIER (BRB) INTEGRITY. THE BRB, WHICH IS FORMED BY TIGHT JUNCTIONS OF RETINAL VASCULAR ENDOTHELIAL CELLS AND RETINAL PIGMENT EPITHELIAL CELLS, BREAKS DOWN EARLY IN DR PATHOGENESIS AND CAUSES VASCULAR PERMEABILITY AND LEAKAGE AS WELL AS INFLAMMATION, LEADING TO LOSS OF RETINAL HOMEOSTASIS AND NEURODEGENERATION. DIABETES-ASSOCIATED FACTORS ALSO DISRUPT GAP JUNCTION INTERCELLULAR COMMUNICATIONS TO FURTHER EXACERBATE DR. THEREFORE, PROTECTING INTERCELLULAR JUNCTIONS REPRESENTS A SIGNIFICANT THERAPEUTIC OPPORTUNITY TO TREAT DR. CONNEXIN43 (CX43) IS A TRANSMEMBRANE PROTEIN COMPONENT OF INTERCELLULAR JUNCTIONS THAT IS INSTRUMENTAL TO BARRIER FUNCTION INTEGRITY, CELL-CELL COMMUNICATION, AND APOPTOSIS. FIRSTSTRING RESEARCH INC. HAS DEVELOPED A THERAPEUTIC PEPTIDE MIMETIC OF CX43, ALPHA-CONNEXIN CARBOXY-TERMINAL (ACT1), THAT STABILIZES INTERCELLULAR JUNCTIONS WHILE TEMPERING HEMICHANNEL ACTIVITY TO PRESERVE BARRIER FUNCTION, REDUCE INJURY SPREAD, AND DECREASE INFLAMMATION. INEXIN IS A STABLE NON-STEROIDAL, PRESERVATIVE-FREE ACT1 EYE DROP FORMULATION VALIDATED IN A COMPREHENSIVE SET OF SAFETY AND EFFICACY STUDIES. FROM THESE STUDIES, WE HYPOTHESIZE THAT INEXIN TREATMENT WILL STABILIZE INTERCELLULAR JUNCTIONS COMPRISING THE BRB TO AMELIORATE DR PATHOPHYSIOLOGY, PRESERVING RETINAL HEALTH AND FUNCTION. TO TEST THIS HYPOTHESIS, WE PROPOSE TO DEMONSTRATE PROOF-OF-CONCEPT EFFICACY OF INEXIN TO MITIGATE DIABETIC RETINOPATHY (AIM 1), AND TO CONFIRM ACT1 BIODISTRIBUTION IN THE DIABETIC EYE FOLLOWING EYE DROP ADMINISTRATION (AIM 2). USING A TRANSLATIONALLY RELEVANT STREPTOZOTOCIN-INDUCED TYPE 1 DIABETIC RAT MODEL, WE PROPOSE TO EVALUATE THE IMPACT OF INEXIN ON DR USING TWO DISTINCT TREATMENT PARADIGMS. THE FIRST INITIATES INEXIN ADMINISTRATION CONCURRENT WITH THE ONSET OF HYPERGLYCEMIA; THE SECOND INITIATES TREATMENT AT THE CLINICAL MANIFESTATION OF RETINAL VASCULAR ABNORMALITIES. WE WILL ALSO CONFIRM ACT1 BIODISTRIBUTION IN THE DIABETIC EYE FOLLOWING TOPICAL OCULAR ADMINISTRATION AND ACT1'S LOCALIZATION TO RETINAL EPITHELIAL AND ENDOTHELIAL CELLS. SUCCESSFUL COMPLETION OF THESE ACTIVITIES WILL PROVIDE PROOF-OF-CONCEPT EFFICACY FOR ACT1'S MECHANISM OF ACTION TRANSLATING TO THERAPEUTIC EFFECTIVENESS IN THE TREATMENT OF DR, WHILE ALSO SUPPORTING PROJECT ADVANCEMENT INTO EFFICACY AND SAFETY STUDIES IN LARGE (NON-RODENT) ANIMAL MODELS OF DR. TRANSLATION INTO THE CLINIC WILL MEAN SIGNIFICANTLY IMPROVED OUTCOMES FOR THE >8M DIABETIC ADULTS IN THE US ALONE.