Autoimmune Ophthalmic Diseases

Autoimmune ophthalmic diseases represent a complex and challenging field, but Protheragen's dedication to scientific excellence and therapeutic innovation has positioned us as a trusted partner in the pursuit of transformative solutions. Through our innovative services, we are committed to providing global pharmaceutical companies with one-stop drug and therapy development solutions.

Introduction to Autoimmune Ophthalmic Diseases

Autoimmune ophthalmic disease drug and therapy development encompasses preclinical research and translational efforts aimed at creating targeted interventions for vision-threatening disorders driven by dysregulated immune responses that attack ocular tissues. These conditions arise when the immune system fails to maintain self-tolerance, leading to chronic inflammation, tissue damage, and progressive visual impairment across multiple ocular structures—including the uvea, cornea, sclera, retina, and lacrimal glands. Preclinical development in this field focuses on elucidating the molecular mechanisms of immune dysregulation, validating disease-specific targets, and evaluating candidate therapies for their ability to modulate immune responses, mitigate tissue injury, and preserve ocular function before advancing to clinical trials.

The preclinical pipeline for autoimmune ophthalmic therapies is defined by its emphasis on targeting pathogenic immune cell subsets, pro-inflammatory cytokines, and autoantigen-driven immune cascades—distinct from infectious or degenerative ocular conditions. Core objectives include restoring immune homeostasis without compromising systemic immune competence, overcoming ocular barriers (such as the blood-ocular barrier) to ensure therapeutic bioavailability, and minimizing off-target effects on delicate ocular tissues. Preclinical studies integrate in vitro immune cell assays, ex vivo ocular tissue models, and in vivo autoimmune disease models to generate robust data on therapeutic efficacy, pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles, all essential for supporting Investigational New Drug (IND) applications.

Fig.1 Classification of autoimmune diseases. (Glover K., et al., 2021)

This development process is tailored to the heterogeneous nature of autoimmune ophthalmic diseases, which include uveitis, Sjögren's syndrome-associated dry eye, Graves' ophthalmopathy, and autoimmune keratitis, among others. Each condition exhibits unique immune pathogenic signatures—for example, T cell-mediated inflammation in uveitis versus B cell and antibody-driven pathology in Graves' ophthalmopathy—requiring customized preclinical strategies. Preclinical validation prioritizes assessments of target engagement, immune modulation specificity, and long-term tissue protection, as many autoimmune ocular disorders follow a relapsing-remitting course with cumulative damage over time. Rigorous preclinical testing also addresses the challenge of translating immune-modulating efficacy from animal models to humans, ensuring candidates are evaluated under conditions that recapitulate key clinical features of human disease.

Key methodologies in preclinical development for these diseases include autoantigen identification, immune cell subset profiling, and functional assays to measure inflammatory mediator production. For example, preclinical studies of uveitis focus on characterizing autoreactive T cell populations—particularly Th17 cells—and their role in driving intraocular inflammation, while dry eye associated with Sjögren's syndrome requires assessment of lacrimal gland immune infiltration and tear film dysfunction. Preclinical models must replicate these disease-specific pathologies to reliably predict therapeutic performance, making model validation a critical step in the development workflow.

Current Status of Autoimmune Ophthalmic Disease Therapy Development

Preclinical research for autoimmune ophthalmic diseases has advanced significantly with the refinement of disease models and the identification of key immune targets. Experimental Autoimmune Uveitis (EAU) remains the gold standard in vivo model for studying posterior uveitis, with the C57BL/6J mouse strain widely used due to its susceptibility to disease induction via subcutaneous injection of interphotoreceptor retinoid binding protein (IRBP) peptide emulsified with Complete Freund's Adjuvant (CFA) and intraperitoneal Bordetella pertussis toxin. This model recapitulates key clinical features of human posterior uveitis, including retinal inflammation, photoreceptor damage, and vascular permeability, enabling robust evaluation of candidate therapies. Recent preclinical studies using EAU have focused on targeting Th17 cells, a critical pathogenic subset, with data demonstrating that IRBP-specific autoreactive T cells can adoptively transfer uveitis to naive recipients, validating these cells as a direct therapeutic target.

Advancements in preclinical target validation have expanded the pipeline of potential therapies beyond broad-spectrum immunosuppressants to include targeted biologics and cell-based interventions. Preclinical studies have demonstrated promise in modulating pro-inflammatory cytokines such as interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), which play pivotal roles in driving ocular inflammation. For example, neutralizing antibodies against IL-17 have shown efficacy in reducing clinical scores and retinal tissue damage in EAU models, while small molecule inhibitors of TNF-α signaling have been validated for their ability to suppress immune cell infiltration in uveitis preclinical systems. Additionally, preclinical research into post-infectious autoimmune uveitis has identified that ocular infection can trigger the generation of autoreactive T cells, opening new avenues for therapies targeting infection-induced immune dysregulation.

Despite progress, preclinical development faces significant challenges, including bridging species-specific differences in immune responses and replicating the chronic, relapsing nature of human autoimmune ophthalmic diseases. Many preclinical models induce acute disease phenotypes, which may not fully recapitulate the long-term tissue remodeling and functional decline observed in patients. Additionally, translating efficacy from EAU and other animal models to humans remains hindered by variations in autoantigen specificity and immune cell subset dynamics between species. Preclinical studies also grapple with optimizing ocular delivery of immune-modulating therapies, as the blood-ocular barrier limits the bioavailability of systemic agents, while topical formulations often fail to penetrate deep ocular tissues affected by conditions like posterior uveitis. These challenges underscore the need for advanced preclinical models and delivery systems to enhance translational predictability.

For more severe or resistant cases, immunosuppressive agents like cyclosporine and azathioprine are utilized to dampen the immune response. Biologics, such as tumor necrosis factor (TNF) inhibitors and interleukin (IL) inhibitors, provide targeted therapy by regulating specific components of the immune system. Additionally, the field is witnessing the advent of gene therapy as a potential therapeutic avenue for genetic conditions with autoimmune attributes.

Table 1. Rare ocular manifestations of various autoimmune diseases. (Glover K., et al., 2021)

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

At Protheragen, we pride ourselves on our comprehensive service offerings dedicated to advancing the development of therapies for autoimmune ophthalmic diseases. We have industry-leading scientists available to guide our clients through every step of the drug and therapeutic development process, from target identification to preclinical studies.

Autoantigen and Immune Target Validation

Protheragen provides comprehensive services to identify and validate autoantigens and immune targets driving autoimmune ophthalmic diseases. This includes autoantigen profiling using patient-derived samples, genomic and proteomic analysis to identify dysregulated immune pathways, and functional validation assays to confirm the role of candidate targets in disease pathogenesis. For T cell-mediated conditions like uveitis, we offer services to characterize autoreactive T cell subsets—including Th17 cells—and assess their ability to induce ocular inflammation using in vitro co-culture assays with ocular tissue cells. Clients can access support for cytokine profiling (IL-17, TNF-α, IFN-γ) and immune cell phenotyping via flow cytometry and immunofluorescence to validate target engagement and immune modulation efficacy.

Custom Autoimmune Disease Model Generation

We develop tailored in vitro, ex vivo, and in vivo models to recapitulate key features of autoimmune ophthalmic diseases. In vitro models include human peripheral blood mononuclear cell (PBMC) cultures, autoreactive T cell lines, and ocular tissue cell co-cultures (retinal pigment epithelium, corneal epithelial cells) to study immune cell-ocular tissue interactions. Ex vivo models use freshly isolated ocular tissues (human donor eyes, rabbit uvea, mouse lacrimal glands) to evaluate therapeutic penetration and immune modulation in a physiological context. In vivo models encompass gold-standard and custom-engineered systems, including EAU in C57BL/6J mice induced by IRBP peptide/CFA, post-infectious uveitis models, and Sjögren's syndrome dry eye models, all subjected to rigorous phenotypic characterization via fundoscopy, histopathological analysis, and immune cell infiltration quantification.

Therapeutic Efficacy Evaluation

Our preclinical efficacy services assess the ability of candidate therapies to modulate immune responses and preserve ocular function in autoimmune ophthalmic disease models. For immune-modulating agents, we conduct in vitro assays to measure T cell proliferation inhibition, cytokine production reduction, and autoantibody neutralization. In vivo efficacy studies evaluate therapeutic impact on disease progression via clinical scoring (uveitis severity, tear production, ocular inflammation), histopathological assessment of tissue damage, and functional endpoints such as retinal electrophysiology. We also offer adoptive transfer assays to evaluate the ability of therapies to block autoreactive T cell-mediated disease, leveraging methodologies validated in post-infectious uveitis research. Combination therapy testing is available to assess synergistic effects of dual-targeted immune modulation.

Ocular Delivery and Formulation Optimization

Protheragen supports the development and optimization of ocular formulations to enhance bioavailability of immune-modulating therapies across target ocular tissues. Services include formulation design for intravitreal, periocular, and topical delivery routes, with a focus on overcoming the blood-ocular barrier for deep tissue penetration. We evaluate formulation performance using in vitro permeation assays (corneal, scleral, and retinal pigment epithelium models) and ex vivo tissue penetration studies. For nanotherapeutic formulations (lipid nanoparticles, polymeric micelles) designed to encapsulate biologics or small molecules, we assess particle size, encapsulation efficiency, release kinetics, and immune compatibility. In vivo distribution studies measure therapeutic concentrations in target tissues (uvea, retina, lacrimal glands) and systemic circulation to optimize dosing and minimize off-target immune suppression.

Immunogenicity and Safety Assessment

We conduct comprehensive preclinical safety studies to evaluate the immunogenicity and toxicity of candidate therapies, adhering to GLP standards and global regulatory guidelines. Immunogenicity assessments include anti-drug antibody (ADA) detection, complement activation assays, and evaluation of immune cell activation status to identify potential hypersensitivity responses. Ocular safety testing encompasses local irritation evaluation, histopathological analysis of ocular tissues to assess inflammation or structural damage, and functional assessments of retinal and corneal integrity. Systemic safety studies measure the impact of immune-modulating therapies on systemic immune function, hematological parameters, and organ integrity to ensure therapies do not induce broad immunosuppression or off-target organ toxicity. All studies generate detailed reports with statistically robust data to support regulatory review.

Molecular Mechanism of Action Analysis

Protheragen offers in-depth mechanistic studies to elucidate how candidate therapies modulate immune responses in autoimmune ophthalmic diseases. Services include gene expression profiling (RNA-seq) to identify dysregulated immune pathways, protein expression analysis via Western blotting and ELISA, and cell sequencing to characterize changes in immune cell subset composition. For T cell-mediated diseases, we assess changes in autoreactive T cell activation, differentiation, and homing to ocular tissues using flow cytometry and in vivo tracking assays. These studies provide critical insights into therapeutic mechanism of action, supporting target validation and enhancing the translational potential of candidate therapies by linking immune modulation to clinical efficacy endpoints.

Types of Autoimmune 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

Why Choose Us?

• Innovative Approach: Protheragen employs a multidisciplinary approach, integrating immunology, molecular biology, and pharmacology to develop targeted therapies for autoimmune ophthalmic diseases.
• Scientific Rigor: Our drug development services are grounded in rigorous scientific research, ensuring that our therapies are based on the most current and evidence-based understanding of autoimmune pathogenesis.
• Customized Solutions: We recognize the heterogeneity of autoimmune ophthalmic diseases and tailor our development strategies to address the specific needs of each condition.

If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

Reference

• Glover Katie, Deepakkumar Mishra, and Thakur Raghu Raj Singh. "Epidemiology of ocular manifestations in autoimmune disease." Frontiers in immunology 12 (2021): 744396.