Congenital Ophthalmic Diseases

Ranging from rare retinal dystrophies to common refractive errors, congenital ophthalmic diseases pose a significant challenge but also an opportunity for innovative therapeutic interventions. At Protheragen, our team of experienced biologists is dedicated to unraveling the complex molecular mechanisms of these debilitating diseases and providing expert therapy development services.

Introduction to Congenital Ophthalmic Diseases

Congenital ophthalmic disease drug and therapy development encompasses the preclinical research and experimental advancement of interventions targeting eye disorders present at birth or early childhood. These conditions are predominantly monogenic (caused by single-gene mutations) or multigenic, affecting critical ocular structures such as the retina, cornea, lens, optic nerve, and associated neural pathways. Examples include Leber Congenital Amaurosis (LCA), retinitis pigmentosa (RP), Stargardt disease, congenital cataracts, and aniridia—each characterized by progressive vision impairment or blindness due to dysfunctional or degenerating ocular cells.

Preclinical development in this field focuses on translating genetic and molecular insights into viable therapeutic candidates through rigorous in vitro and in vivo testing. Core objectives include identifying disease-causing mechanisms, validating molecular targets, optimizing therapeutic modalities, and evaluating safety and efficacy prior to clinical trials. Key methodologies involve patient-derived disease modeling, gene editing, pharmacodynamic analysis, and ocular-specific efficacy assessments. For instance, LCA caused by AIPL1 gene mutations disrupts photoreceptor function, necessitating preclinical models that recapitulate human disease phenotypes to test targeted therapies, such as pharmacological agents rescuing faulty protein expression or splice-modulating agents correcting gene transcript errors.

Fig.1 Application of AI in ophthalmic diseases. (Wu, X, et al., 2020)

Therapeutic modalities under preclinical investigation include gene augmentation, gene editing (CRISPR/Cas9), optogenetics, pharmacological chaperones, and splice-switching oligonucleotides. Each approach requires specialized preclinical validation to address ocular-specific challenges, such as delivering therapies to target cells (e.g., photoreceptors, retinal pigment epithelium), overcoming the blood-retinal barrier, and ensuring long-term safety without inducing inflammation or tissue damage. Preclinical development also involves optimizing routes of administration—from eye drops for topical agents to intravitreal or subretinal injections for biologics—while confirming bioavailability and tissue distribution within ocular structures.

Current Status of Congenital Ophthalmic Disease Therapy Development

Preclinical research in congenital ophthalmic diseases has advanced rapidly, fueled by breakthroughs in gene editing, organoid technology and disease modeling. Patient-derived induced pluripotent stem cell (iPSC) models, which generate 3D ocular organoids recapitulating disease phenotypes with high fidelity, overcome limitations of direct patient tissue sampling and enable personalized therapeutic testing—for example, iPSC-derived retinal organoids from LCA patients with AIPL1 mutations validate pharmacologic agents targeting mutations. Gene therapy, particularly via adeno-associated virus (AAV) vectors, is a key focus, with preclinical efficacy shown in correcting genetic defects in LCA, RP and Best disease; optogenetic therapies also offer promise for genetically heterogeneous conditions like RP by bypassing dysfunctional photoreceptors.

Despite such progress, preclinical development faces notable challenges, including the need for rigorous validation of ocular disease models to match human physiology, scaling long-term safety/efficacy testing, optimizing vector tropism, minimizing immune responses and developing sensitive functional assays—gaps addressed by advances in imaging technologies and genomic bioinformatics pipelines. Preclinical pipelines are expanding to combination therapies, such as gene editing paired with pharmacologic agents for LCA, while integrated biobanking and genomic sequencing accelerate target identification via patient-derived biospecimens.

Table 1. Clinical trials registered on clinicaltrials.gov for different congenital ophthalmic diseases. (Niu Y., et al., 2024)

Disclaimer: Protheragen focuses on providing preclinical research service. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.

Our Services

Protheragen leads the way in pioneering groundbreaking drug and therapy solutions for congenital ophthalmic disorders. Our extensive range of services includes gene therapy, gene editing, and the creation of innovative pharmaceutical compounds. By harnessing state-of-the-art technologies, we target and rectify genetic mutations at their core, providing a beacon of hope for conditions that were once deemed untreatable.

Patient-Derived and Gene-Edited Disease Modeling

Protheragen can generate customized in vitro and in vivo disease models to recapitulate congenital ophthalmic conditions, including LCA, RP, Stargardt disease, congenital cataracts, and optic nerve disorders. Services include the development of iPSC-derived ocular organoids (optic cups, retinal pigment epithelium) from patient fibroblasts, peripheral blood mononuclear cells (PBMCs), or gene-edited cell lines. These models enable direct comparison of wild-type and mutant phenotypes, facilitating phenotypic analysis, therapeutic rescue experiments, and compound screening. We also offer gene-edited rodent models (mouse, rat) with targeted mutations in genes linked to congenital ocular diseases, providing stable, heritable models for in vivo efficacy and safety testing. All models undergo rigorous validation to ensure phenotypic consistency and relevance to human disease, including assessment of key markers, structural integrity, and functional deficits.

Genomic Analysis and Target Validation

We provide comprehensive genomic services to identify and validate causal variants in congenital ophthalmic diseases. Offerings include next-generation sequencing (NGS) of exomes and genomes, variant calling, annotation, and prioritization using advanced bioinformatics pipelines. Protheragen can analyze client-provided biospecimens (DNA, RNA, cell lines) to characterize novel disease genes, classify variants of uncertain significance, and establish genotype-phenotype correlations. Functional validation services include gene expression analysis, protein localization studies, and gene editing to confirm the role of candidate targets in disease pathogenesis. These services support target identification for gene therapies, pharmacologic agents, and other therapeutic modalities, ensuring clients focus on high-potential targets with clear mechanistic links to disease.

Preclinical Efficacy and Pharmacodynamic Testing

Protheragen delivers tailored efficacy testing services to evaluate therapeutic candidates across multiple modalities. For gene therapies, we assess vector tropism, transgene expression, and functional rescue in in vitro and in vivo models, using techniques such as immunofluorescence, Western blotting, and qPCR. Optogenetic therapy testing includes evaluation of light sensitivity, neural pathway activation, and visual function using full-field electroretinography (ffERG) and optical coherence tomography (OCT). Pharmacological testing encompasses screening of small molecules, biologics, splice-switching oligonucleotides, and chaperone drugs, with assessments of cell viability, phenotypic rescue, and target engagement. We also offer specialized ocular pharmacokinetic (PK) analysis, including tissue distribution studies in corneal, retinal, and vitreous tissues, to optimize routes of administration (eye drops, intravitreal injection, subretinal injection).

Safety Assessment and Toxicology

Our preclinical safety services focus on evaluating ocular and systemic toxicity of therapeutic candidates, critical for regulatory compliance. Offerings include ocular irritation testing, intraocular pressure monitoring, and histopathological analysis of ocular tissues (cornea, retina, choroid, optic nerve) to detect inflammation, degeneration, or structural damage. We also assess immune responses to gene therapies, including vector-specific antibody production and inflammatory cytokine profiling. Toxicology studies are conducted in relevant animal models, with semi-quantitative scoring systems to quantify ocular toxicity and ensure candidates meet safety thresholds for clinical advancement. Protheragen’s safety assessments integrate with efficacy data to provide a comprehensive preclinical profile, supporting IND-enabling studies.

Types of Congenital Ophthalmic Diseases

Our Therapeutics Development Solutions

Diagnostics Development

• Karyotype Analysis Service
• Omics Analysis Service
• Biomarker Development Service
• Artificial Intelligence Service

Therapeutic Development

• Small Molecule Drug
• Cell Therapy
• Gene Therapy
• Therapeutic Antibody
• Therapeutic Peptide
• Therapeutic Protein

Preclinical Research

• Pharmacodynamics Study Services
• Pharmacokinetics Study Services
• Drug Safety Evaluation Services

Disease Models

• Cell-based Models Development Service
• Organoid Models Development Service
• Animal Models Development Services

As we continue to advance our research and development, our commitment to excellence and innovation remains unwavering, ensuring that Protheragen remains at the forefront of congenital ophthalmic disease therapeutics. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

• Wu, Xiaohang, et al. "Application of artificial intelligence in anterior segment ophthalmic diseases: diversity and standardization." Annals of Translational Medicine 8.11 (2020).
• Niu, Yifei, et al. "Regenerative treatment of ophthalmic diseases with stem cells: Principles, progress, and challenges." Advances in Ophthalmology Practice and Research (2024).