SBIR-STTR Award

Diseases of the retina, either genetically determined or secondary to systemic disease, are the leading cause of blindness in the industrialized world. More than 5.3 million Americans are affected by diabetic retinopathy. Another 1.6 million Americans over age 60 have age-related macular degeneration. Retinopathy of prematurity is a major cause of blindness in premature infants maintained by oxygen supplementation during the postnatal period. Using gene knockdown technology, this SBIR aims to validate the zebrafish embryo as a whole animal model for human eye diseases that result from vascular defects. This SBIR will characterize embryogenesis and patterning, and the formation of the vasculature of the zebrafish eye. Zebrafish is a good animal model for eye vascular disease. Orthologs of many genes involved in angiogenesis in mammals have been identified in zebrafish. Assays and drug treatment can easily be performed on the zebrafish embryo because of its rapid ex-utero development. Embryos are transparent, permitting visual observation of defects in development and angiogenesis in the eye and elsewhere. Furthermore, early stage embryos do not require blood for normal development, obtaining sufficient oxygen by diffusion. This permits performance of gene knockdown experiments, which would result in early lethality in mammalian models.

Thesaurus Terms:
disease /disorder model, eye disorder, gene targeting, genetically modified animal, model design /development angiogenesis, angiography, blood vessel disorder, embryogenesis, eye circulation, genetic translation, nonmammalian vertebrate embryology, oligonucleotide, retina disorder biotechnology, confocal scanning microscopy, embryo /fetus, histology, zebrafish

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the two leading causes of blindness in adults in the industrialized world. Both conditions involve vascular abnormalities, proliferation and leakage of new blood vessels. Retinopathy of prematurity (ROP) is a major cause of newborn blindness in premature infants maintained by oxygen supplementation during the postnatal period. This disease involves intense neovascularization of the retina and leads to retinal detachment. Another cause of blindness is corneal neovascularization, which often results from injury and infection in the cornea. Current mammalian models for ocular neovascularization require lengthy, tedious surgical manipulation and do not always result in improved vision; an alternative rapid, less invasive animal model for studying the process of ocular neovascularization and assessing drug effects will facilitate identification of new therapeutics. Phase I research validated zebrafish as a model for vascularization of the eye. Phase II research will develop a zebrafish model for ocular vascularization that can be used to screen drugs that would be effective in treating debilitating diseases involving neovascularization.

Thesaurus Terms:
disease /disorder model, eye disorder, genetically modified animal, model design /development, zebrafish angiogenesis, angiography, blood vessel disorder, developmental genetics, drug screening /evaluation, eye circulation, nonmammalian vertebrate embryology, retina disorder biotechnology, histology

Project Terms:
0-6 weeks old; 21+ years old; Adult; Age related macular degeneration; Animal Model; Animal Models and Related Studies; Antibodies; Assay; Bioassay; Biologic Assays; Biological Assay; Blindness; Blood Vessels; Brachydanio rerio; Clinical Treatment; Clinical Trials; Clinical Trials, Phase I; Clinical Trials, Unspecified; Cornea; Corneal Angiogenesis; Corneal Neovascularization; Danio rerio; Diabetic Retinopathy; Disease; Disorder; Drug Evaluation, Preclinical; Drug Screening; Drugs; Early-Stage Clinical Trials; Evaluation Studies, Drug, Pre-Clinical; Evaluation Studies, Drug, Preclinical; Extravasation; Eye; Eye diseases; Eyeball; Gene Targeting; Genes; Human, Adult; Infant, Newborn; Infant, Premature; Infection; Injection of therapeutic agent; Injections; Injury; Knockout Mice; Leakage; Libraries; Maculopathy, Age-Related; Mammals, Mice; Medication; Mice; Mice, Knock-out; Mice, Knockout; Modeling; Murine; Mus; Newborn Infant; Newborns; Null Mouse; O element; O2 element; Operation; Operative Procedures; Operative Surgical Procedures; Oxygen; Pharmaceutic Preparations; Pharmaceutical Preparations; Phase; Phase 1 Clinical Trials; Phase I Clinical Trials; Phase I Study; Phenotype; Preclinical Drug Evaluation; Premature Infant; Process; Research; Retina; Retinal Detachment; Retinopathy of Prematurity; Retrolental Fibroplasia; Retrolental Fibroplasias; Screening procedure; Sight; Spillage; Staining method; Stainings; Stains; Supplementation; Surgical; Surgical Interventions; Surgical Procedure; Targetings, Gene; Therapeutic; Vascularization; Vision; Zebra Danio; Zebra Fish; Zebrafish; adult human (21+); clinical investigation; corneal; disease/disorder; drug/agent; eye disorder; improved; knock-down; model organism; neovascularization; new therapeutics; newborn human (0-6 weeks); next generation therapeutics; novel therapeutics; ocular neovascularization; ophthalmopathy; phase 1 study; phase 1 trial; phase I trial; postnatal; premature baby; premature infant human; premature retinopathy; preterm baby; preterm infant; preterm infant human; preterm neonate; protocol, phase I; retina detachment; screening; screenings; senile macular disease; surgery; trial regimen; trial treatment; vascular