Ignite Creation Date:
2024-05-11 @ 8:31 AM
Last Modification Date:
2024-10-26 @ 3:29 PM
Study NCT ID:
NCT06408701
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-10
First Post:
2024-05-07
Brief Title:
Modeling Ocular Developmental Diseases From 3D Cultures of Optic Vesicle Organoids Derived From hiPSCs of Patients With Ocular Malformations
Sponsor:
University Hospital Toulouse
Organization:
University Hospital Toulouse
Study Overview
Official Title:
Modeling Ocular Developmental Diseases From 3D Cultures of Optic Vesicle Organoids Derived From hiPSCs of Patients With Ocular Malformations
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
OrganoEye
Brief Summary:
Ocular morphogenesis is a complex process starting as early as the 4th week of embryonic life involving interactions between varioustissues of different origin and conserved genes Anomalies in ocular development often of genetic origin pose diagnostic and therapeutic challenges Animal models are limited so human-induced pluripotent stem cell hiPSC-derived optic vesicle containing brain organoids OVBOs offer a promising alternative These pathological OVBOs created from patients cells with ocular malformations allow for the study of underlying molecular mechanisms and testing of therapies
Detailed Description:
The eyes ability to perform its visual functions depends on its three-dimensional structure Ocular morphogenesis is a complex process that begins in humans as early as the 4th week of embryonic life requiring coordinated interactions between various embryologically diverse tissues involving highly conserved genes Cardozo MJ 2023 Disruption in any of these stages of ocular development due to genetic toxic or environmental factors can result in growth or formation defects of the eye globe Among the most frequent ocular developmental anomalies there are micro-anophthalmia coloboma anterior segment dysgenesis and aniridia Plaisancie J 2019 Most of these anomalies are of genetic origin The primary obstacle in understanding these diseases is the lack of easily accessible tissue for sampling which would allow for expression analyses and the study of underlying molecular mechanisms
In this group of pathologies understanding the pathophysiological mechanisms and therapeutic development was until recently quite limited and relied almost exclusively on the establishment of genetically modified animal models a procedure that is lengthy costly and cumbersome Moreover routine diagnostic use of this model is not feasible in a hospital setting Therefore it is necessary to develop new tools and models to advance the understanding and management of these pathologies The use of human induced pluripotent stem cells hiPSCs now allows for the understanding of the complexity of early organ development through the generation of 3D cellular models Indeed recent studies have shown that hiPSC-derived brain organoids retain in a specific culture environment the intrinsic capacity to develop optic vesicles OV mimicking early physiological ocular development and containing various ocular tissues Gabriel E 2021
The optic vesicle organoid OVBO model thus represents a preferred alternative to the animal model in studying pathophysiological mechanisms and their use in preclinical trials In addition to ethical and financial considerations the latter has numerous advantages particularly allowing the study of defective mechanisms directly from patient cells precision medicine Researchers have already developed the OVBO model from control hiPSC lines and have characterized the model under physiological conditions
The next step in understanding the model and proving its utility in patients relies on studying the induced phenotype in OVBO models generated from hiPSCs from patients with genetically characterized ocular malformations These pathological OVBO models will allow for detailed study of the molecular and cellular bases involved in these patients Once the relevance of the model is demonstrated in modeling developmental pathologies of the eye researchers will attempt to show that the OVBO model constitutes a robust alternative to the murine model in preclinical trials
In this group of pathologies understanding the pathophysiological mechanisms and therapeutic development was until recently quite limited and relied almost exclusively on the establishment of genetically modified animal models a procedure that is lengthy costly and cumbersome Moreover routine diagnostic use of this model is not feasible in a hospital setting Therefore it is necessary to develop new tools and models to advance the understanding and management of these pathologies The use of human induced pluripotent stem cells hiPSCs now allows for the understanding of the complexity of early organ development through the generation of 3D cellular models Indeed recent studies have shown that hiPSC-derived brain organoids retain in a specific culture environment the intrinsic capacity to develop optic vesicles OV mimicking early physiological ocular development and containing various ocular tissues Gabriel E 2021
The optic vesicle organoid OVBO model thus represents a preferred alternative to the animal model in studying pathophysiological mechanisms and their use in preclinical trials In addition to ethical and financial considerations the latter has numerous advantages particularly allowing the study of defective mechanisms directly from patient cells precision medicine Researchers have already developed the OVBO model from control hiPSC lines and have characterized the model under physiological conditions
The next step in understanding the model and proving its utility in patients relies on studying the induced phenotype in OVBO models generated from hiPSCs from patients with genetically characterized ocular malformations These pathological OVBO models will allow for detailed study of the molecular and cellular bases involved in these patients Once the relevance of the model is demonstrated in modeling developmental pathologies of the eye researchers will attempt to show that the OVBO model constitutes a robust alternative to the murine model in preclinical trials
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None