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- Persistent Fetal Vasculature (PFV)
The inexorable fetal vasculature (PFV) is complex in its presentation, rendering its diagnosis and therapeutics quite difficult. As a research service provider, Protheragen offers customized diagnostics and therapeutics development services.
Persistent Fetal Vasculature (PFV) is a hereditary ocular abnormality whose pathogenesis is associated with the abnormal development of the fetal eye. An embryo is healthy when features like the hyaloid vascular system that supplies the developing lens and retina in the early stages are fully formed. This vascular system, however, is designed to recede, only to leave behind a prominently used pliable structure called the Cloquet canal. In PFV cases, the entirety or parts of the hyaloid vasculature system remain, which leads to overdevelopment of the optic nerve head leading to other ocular parts, like the lens and ciliary process, resulting in abnormally formed posterior structures.
Fig.1 Pathological study of persistent fetal vasculature. (Pauzuolyte V., et al., 2023)There can be a multitude of structural and functional deficiencies in the vision. For instance, persistent fetal vasculature syndrome complications may include ocular and systemic associated congenital anomalies of the lens. Retinal detachment is also a common complication, as the traction exerted by the persistent vessels can pull on the retina. Other conditions like angle-closure glaucoma may occur because of anterior segment dysgenesis which leads to abnormal propulsion of fetal tissue, and obstruction of the aqueous outflow pathways.
Genetic Testing
Testing for PFV usually includes finding the relevant mutations associated with the disorder using genetic examination. PFV is connected to many different genes. Some examples the literature provide, an autosomal recessive inheritance was noted for some cases having mutations at ATOH7 gene at 10q21.3. An Egyptian family with a PFV had a different dominant pattern of inheritance which was noted earlier. Also, in bilateral PFV cases, some mutations were found NDP and COX15 genes located on chromosome 10.
Biomarker Identification
One other part of molecular diagnostics is detecting potential biomarkers. Biomarkers include molecules like proteins and nucleic acids that may take part in the onset and progression of PFV. For example, some studies tried to determine the role of vascular endothelial growth factor (VEGF) and placental growth factor in hyaloid vasculature regression and their abnormal levels as potential biomarkers for PFV.
At Protheragen, we offer a comprehensive range of services for Persistent Fetal Vasculature diagnostics and therapeutics development. Our state-of-the-art facilities and a team of experienced scientists enable us to conduct in-depth research and development in this field.
Protheragen provides comprehensive target identification and validation services to help clients identify and characterize key molecular targets involved in PFV pathogenesis. These services include transcriptomic and proteomic profiling of human PFV samples and preclinical models using sc-RNAseq, immunohistochemistry, and mass spectrometry, enabling the identification of differentially expressed genes, proteins, and cell signaling pathways associated with abnormal hyaloidal vascular regression. We conduct functional validation studies using in vitro cell models (including human retinal endothelial cells, hyalocytes, and neural crest-derived cells) and in vivo genetic models to confirm the role of candidate targets in PFV development, assessing parameters such as vascular proliferation, fibrosis, and cell survival.
Our target validation services also include the evaluation of target druggability, using in silico modeling and high-throughput screening to assess whether candidate targets can be modulated by small molecules, biologics, or gene therapies. Protheragen's team leverages its expertise in PFV genetics to prioritize targets with known associations with the disorder, such as Fz5, NDP, and neogenin, while also identifying novel targets through unbiased profiling—ensuring that clients have access to the most promising therapeutic opportunities.
Protheragen offers high-throughput and high-content screening services to identify lead compounds with potential efficacy in treating PFV, along with subsequent optimization to enhance potency, selectivity, and pharmacokinetic properties. Our screening platforms utilize in vitro models that recapitulate key PFV phenotypes, including human retinal endothelial cell proliferation assays, hyaloid vessel regression models, and fibrosis assays (assessing collagen deposition and myofibroblast activation). We also employ 3D organoid models derived from human pluripotent stem cells to mimic the complex ocular microenvironment, providing a more physiologically relevant system for compound screening.
For lead compound optimization, Protheragen conducts structure-activity relationship (SAR) analysis, pharmacokinetic (PK) profiling, and toxicity screening to refine compound properties and reduce off-target effects. We assess compound absorption, distribution, metabolism, and excretion (ADME) in preclinical models, along with ocular bioavailability—critical for ensuring that compounds reach the target site within the eye. Our team also evaluates compound stability and formulation compatibility, supporting the development of delivery systems tailored to ocular administration (e.g., intravitreal injections, eye drops) that maximize therapeutic efficacy while minimizing systemic exposure.
Protheragen provides rigorous preclinical efficacy evaluation services to assess the therapeutic potential of lead compounds and therapies in PFV models. We utilize a range of validated preclinical models, including genetic knockout mice (Fz5, NDP, and neogenin mutants), which exhibit key PFV phenotypes such as retained hyaloidal vessels, retinal dysplasia, and fibrosis. Our efficacy studies include both short-term and long-term assessments, measuring endpoints such as hyaloidal vessel regression, reduction in retrolenticular membrane formation, preservation of retinal structure and function, and improvement in visual outcomes (assessed via electroretinography and behavioral testing).
We employ advanced ophthalmic imaging techniques to non-invasively monitor disease progression and therapeutic response, including spectral-domain OCT (SD-OCT) for high-resolution visualization of retinal layers and vitreous structures, fundus fluorescence angiography (FFA) for assessing vascular integrity, and infrared fundus imaging for evaluating retinal morphology. Protheragen also conducts histopathological and molecular analyses of ocular tissues post-study, including immunohistochemistry for markers of vascularization, fibrosis, and cell apoptosis, to provide mechanistic insights into therapeutic efficacy.
Safety is a critical component of PFV preclinical drug development, and Protheragen offers comprehensive safety assessment services to evaluate the potential ocular and systemic toxicity of candidate therapies. Our safety studies are designed to comply with GLP (Good Laboratory Practice) standards and regulatory requirements, utilizing relevant preclinical models (including mice, rats, and rabbits) to assess toxicity following ocular administration (intravitreal, subretinal, or topical). We evaluate acute, subacute, and chronic toxicity, measuring endpoints such as ocular irritation, inflammation, corneal opacity, retinal damage, and systemic adverse effects.
Our safety assessment services also include immunogenicity testing to evaluate the potential for candidate biologics (e.g., antibodies, gene therapies) to induce an immune response, as well as genotoxicity and carcinogenicity testing when required. Protheragen's team of toxicologists and ophthalmic experts works closely with clients to design tailored safety studies that address the unique risks associated with PFV therapies, ensuring that potential safety concerns are identified early in the development process and mitigated through formulation or dosage adjustments.
Protheragen's preclinical research services for PFV are designed to provide a solid foundation for the development of effective therapies. We conduct in vitro studies using cell lines and organoids to understand the molecular mechanisms underlying PFV. For example, we use retinal cell lines to study the effects of genetic mutations on cell behavior and the role of signaling pathways in the development of PFV-related phenotypes.
In vivo preclinical studies are also a key part of our services. We use animal models, such as mice and rabbits, to test the safety and efficacy of potential therapeutics. These animal models are carefully selected based on their ability to mimic the human PFV condition. If you are interested in our services, please feel free to contact us.
References
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
As a research service provider, Protehragen offers a comprehensive range of cutting-edge services to advance the development of innovative therapies and unlock the future of rare eye disease therapeutics.
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