Ocular Neoplastic Diseases

Ocular neoplastic diseases refer to the development of tumors or cancerous growths within the eye and surrounding ocular structures. As a provider of research services, Protheragen offers comprehensive drug and therapy development services tailored to ocular neoplastic diseases.

Introduction to Ocular Neoplastic Diseases

Ocular neoplastic disease drug and therapy development encompasses preclinical research and translational efforts focused on creating targeted interventions for malignant and benign tumors affecting ocular tissues. These tumors arise from diverse ocular structures, including the uvea (iris, ciliary body, choroid), retina, conjunctiva, lacrimal gland, and orbital soft tissues, with varying pathogenic mechanisms and clinical aggressiveness. Preclinical development in this field prioritizes elucidating tumor initiation and progression pathways, validating oncogenic targets, and evaluating candidate therapies for their ability to inhibit tumor growth, suppress metastasis, and preserve ocular function—all while minimizing damage to surrounding healthy tissues before advancing to clinical trials.

The preclinical pipeline for ocular neoplastic therapies is distinguished by its focus on addressing the unique challenges of ocular oncology, including the blood-ocular barrier (BOB) that limits therapeutic bioavailability to intraocular tumors, the need for tissue-sparing interventions to avoid vision loss, and the management of metastatic phenotypes—particularly for aggressive subtypes like uveal melanoma, which exhibits high propensity for hepatic metastasis. Core objectives include optimizing tumor-specific targeting, enhancing intraocular drug penetration, and evaluating both direct antitumor efficacy and indirect effects on tumor microenvironment (TME) components such as angiogenic vessels and immune cells. Preclinical studies integrate in vitro tumor cell assays, ex vivo ocular tissue models, and in vivo tumor xenograft or genetically engineered models to generate robust data on pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and safety—critical for supporting Investigational New Drug (IND) applications.

Fig.1 Photomicrographs of the same tissue illustrating the IHC staining pattern of a complex tumor of the gland of the third eyelid. (A) Cytokeratin, (B) vimentin, (C) SMA. (Dubielzig R. R., et al., 2016)

This development process is tailored to the heterogeneity of ocular neoplasms, which range from rare, aggressive malignancies (e.g., uveal melanoma, retinoblastoma) to more indolent tumors (e.g., conjunctival squamous cell carcinoma). Each subtype exhibits distinct molecular signatures—for example, GNAQ/GNA11 mutations in uveal melanoma versus RB1 gene inactivation in retinoblastoma—requiring customized preclinical strategies. Preclinical validation prioritizes assessments of target engagement, tumor regression, metastasis suppression, and ocular tissue tolerance, as traditional therapies such as enucleation, radiotherapy, or systemic chemotherapy often cause irreversible ocular damage or fail to control advanced disease. Rigorous preclinical testing also addresses the challenge of translating efficacy from animal models to humans, ensuring candidates are evaluated under conditions that recapitulate key clinical features of human ocular tumors, including TME composition and metastatic potential.

Current Status of Ocular Neoplastic Disease Therapy Development

Preclinical research for ocular neoplastic diseases has advanced significantly with the emergence of targeted therapies and precision drug delivery systems, moving beyond traditional cytotoxic agents to more tumor-specific interventions. Nucleic acid aptamer conjugate drugs (ApDCs) have emerged as a promising class of targeted therapeutics, leveraging aptamers to specifically bind tumor cell surface markers and deliver cytotoxic payloads, minimizing off-target effects on healthy ocular tissues. Preclinical studies using ApDCs for uveal melanoma have demonstrated robust efficacy in inhibiting intraocular tumor growth and reducing hepatic metastasis in animal models, with mechanisms involving precise payload release into tumor cells to induce apoptosis while sparing adjacent healthy tissues. Additionally, targeted small molecule inhibitors of oncogenic pathways—such as MEK inhibitors for uveal melanoma driven by GNAQ/GNA11 mutations—have shown preclinical efficacy in suppressing tumor proliferation, though challenges remain in optimizing intraocular bioavailability and overcoming acquired resistance.

Advancements in preclinical model development have enhanced the translational potential of ocular neoplastic therapies. Genetically engineered mouse models (GEMMs) expressing oncogenic mutations specific to ocular tumors, such as GNAQ for uveal melanoma, recapitulate spontaneous tumor formation and metastatic progression more accurately than traditional xenograft models. Human-derived tumor organoids, generated from patient ocular tumor samples, provide a personalized preclinical platform to evaluate therapy response, including sensitivity to ApDCs, targeted inhibitors, and immunotherapies. Preclinical immunotherapy research has also gained traction, with studies exploring immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells to modulate the ocular TME—though the immunosuppressive nature of intraocular tissues presents barriers to efficacy. These preclinical advancements have expanded the therapeutic pipeline, yet challenges persist in translating systemic therapy efficacy to intraocular tumors due to BOB limitations and balancing antitumor activity with ocular tissue safety.

Table 1. Clinical trials registered on clinicaltrials.gov for different ocular neoplastic 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

Ocular neoplastic diseases represent a significant challenge in the field of ophthalmology, but Protheragen's unwavering commitment to innovation and excellence in drug and therapy development is driving meaningful progress. By combining cutting-edge science and expertise, our company provides customized solutions to pharmaceutical companies around the world.

Oncogenic Target Identification and Validation

Protheragen provides comprehensive services to identify and validate oncogenic drivers and therapeutic targets in ocular neoplasms. This includes genomic and transcriptomic profiling of patient-derived tumor samples via whole-exome sequencing (WES), RNA sequencing (RNA-seq), and copy number variation (CNV) analysis to detect disease-specific mutations (e.g., GNAQ/GNA11, RB1) and dysregulated pathways. We offer functional validation assays to confirm the oncogenic role of candidate targets, including in vitro tumor cell proliferation, migration, and apoptosis assays using gene knockout/knockdown or overexpression systems. Clients can access support for target engagement studies, including binding affinity analysis for aptamers, antibodies, and small molecules, as well as downstream signaling pathway characterization via Western blotting, immunofluorescence, and qPCR to validate target inhibition efficacy.

Custom Ocular Tumor Model Generation

We develop tailored in vitro, ex vivo, and in vivo models to recapitulate key features of ocular neoplastic diseases. In vitro models include patient-derived tumor cell lines, 3D tumor organoids, and co-culture systems with TME components (endothelial cells, immune cells) to study tumor-stroma interactions. Ex vivo models use freshly isolated ocular tissues (human donor eyes, rabbit uvea, mouse retinas) to evaluate therapeutic penetration, tumor cell killing, and tissue compatibility in a physiological context. In vivo models encompass PDX models of uveal melanoma, retinoblastoma, and orbital tumors, as well as GEMMs engineered to express ocular tumor-specific oncogenic mutations. All models undergo rigorous phenotypic characterization, including tumor growth kinetics, intraocular localization, metastatic burden (via bioluminescent imaging), and histopathological analysis of tumor architecture and TME composition.

Therapeutic Efficacy Evaluation

Our preclinical efficacy services assess the antitumor activity of candidate therapies across multiple ocular neoplasm models. For targeted agents and ApDCs, we conduct in vitro assays to measure tumor cell viability, apoptosis induction, and migration/invasion inhibition, including dose-response curves and time-kill analyses. In vivo efficacy studies evaluate tumor regression via caliper measurements (orbital tumors) or ocular imaging (intraocular tumors), metastatic suppression via organ-specific tumor burden quantification, and survival analysis. For immunotherapies, we assess TME immune cell infiltration (CD8+ T cells, macrophages) and cytokine profile changes (IFN-γ, TNF-α) via flow cytometry and ELISA. We also offer combination therapy testing to evaluate synergistic effects of dual-targeted approaches—such as ApDCs combined with MEK inhibitors—and resistance mechanism analysis to inform treatment optimization.

Ocular Delivery and Formulation Optimization

Protheragen supports the development and optimization of ocular formulations to enhance bioavailability of antitumor therapies across target ocular tissues. Services include formulation design for intravitreal, periocular, and intra-arterial delivery routes, with a focus on overcoming the BOB to improve intraocular tumor penetration. For conjugate therapies (ApDCs), nanotherapeutics (lipid nanoparticles, polymeric micelles), and biologics, we assess formulation stability, particle size, encapsulation efficiency, and controlled release kinetics. In vitro permeation assays using corneal, scleral, and retinal pigment epithelium (RPE) models evaluate therapeutic penetration, while in vivo distribution studies measure drug concentrations in target tissues (uvea, retina, orbital soft tissues) and systemic organs to optimize dosing and minimize off-target toxicity.

Toxicology and Safety Assessment

We conduct comprehensive preclinical safety studies to evaluate the ocular and systemic toxicity of candidate therapies, adhering to GLP standards and global regulatory guidelines. Ocular safety testing includes local irritation evaluation, histopathological analysis of ocular tissues (retina, cornea, uvea) to assess structural damage or inflammation, and functional assessments (electroretinography, visual acuity testing) to evaluate vision preservation. Systemic toxicity studies measure hematological parameters, organ function, and body weight changes, with a focus on organs prone to metastasis (liver, lungs) for ocular tumors like uveal melanoma. For immunotherapies and conjugate drugs, we evaluate immunogenicity (anti-drug antibody detection) and off-target cytotoxicity to healthy cells. All studies generate detailed reports with statistically robust data to support regulatory review and clinical trial design.

Tumor Microenvironment and Metastasis Analysis

Protheragen offers specialized services to characterize the ocular tumor microenvironment and evaluate therapeutic effects on metastasis. This includes TME profiling to quantify angiogenic vessel density, immune cell subsets, and extracellular matrix components via immunohistochemistry and cell sequencing. For metastatic ocular tumors, we provide in vitro migration and invasion assays, as well as in vivo metastasis tracking using bioluminescent or fluorescent labeling to monitor dissemination to target organs (liver, lungs). We also assess therapeutic effects on key metastasis drivers, including epithelial-mesenchymal transition (EMT) markers and matrix metalloproteinase (MMP) activity, to validate metastasis suppression efficacy. These studies provide critical insights into therapy-induced changes in tumor biology and metastatic potential, enhancing translational predictability.

Types of Ocular Neoplastic 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

Protheragen conducts rigorous preclinical studies to evaluate the safety and efficacy of new therapeutic agents. This includes in vitro and in vivo models to assess drug activity and pharmacokinetics. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

• Dubielzig, Richard R. "Tumors of the eye." Tumors in domestic animals (2016): 892-922.
• Niu, Yifei, et al. "Regenerative treatment of ophthalmic diseases with stem cells: Principles, progress, and challenges." Advances in Ophthalmology Practice and Research (2024).