Keratoconus

Keratoconus is a degenerative eye condition characterized by the thinning and steepening of the cornea, leading to irregular astigmatism and significant visual impairment. As a research services company, Protheragen is committed to providing professional Keratoconus diagnostics and therapeutic development solutions.

Overview of Keratoconus

Keratoconus is a complex ocular condition characterized by the progressive thinning and conical distortion of the cornea, leading to visual impairment. Recognized as a bilateral yet asymmetrical disease, keratoconus represents a significant challenge to vision health due to its impact on corneal structure and function. The cornea thins and assumes a more cone-like or irregular shape, resulting in irregular astigmatism and significant visual disturbances. Typically emerging in individuals during their second to third decades of life, this condition is notably non-discriminatory, affecting all ethnicities and genders alike. Traditionally thought to be non-inflammatory, contemporary research indicates that inflammatory responses may indeed play a role in its pathophysiology, thereby unlocking new avenues for targeted therapeutic strategies.

Fig.1 Flowchart for keratoconus therapeutics. (Santodomingo-Rubido J., et al., 2022)

Diagnostics Development for Keratoconus

Therapeutics Development for Keratoconus

• Gene Therapies
  The genetic component of keratoconus is substantial, with heritability estimates ranging from 15 to 67 times higher risk among individuals with a family history of the disease. Twin studies and family linkage analyses have identified several chromosomal loci associated with keratoconus, including regions on chromosomes 5q32-33, 14q11.2, and 16q22.3-q23.1. These findings underscore the complexity of the genetic landscape in keratoconus and the potential for targeted gene therapy approaches.
• Drug Therapies
  Drug therapies for keratoconus are in developmental stages, focusing on agents that can modulate the biomechanical properties of the cornea and inhibit the enzymatic degradation of collagen. For instance, riboflavin and ultraviolet A (UVA) cross-linking therapy has shown promise in stabilizing the corneal matrix by forming additional covalent bonds between collagen fibers.
• Innovative Therapies
  Innovative therapies offer novel approaches to keratoconus therapy, including stem cell therapy and bioengineered corneal substitutes. These methods aim to regenerate the corneal stroma or replace it with tissue-engineered constructs, potentially restoring normal corneal architecture and function.

Our Services

Protheragen is at the forefront of developing innovative therapeutics for keratoconus. Our integrated service offerings encompass the entire drug development pipeline, from conceptualization through preclinical evaluation to ensure optimal therapeutic efficacy and safety.

Keratoconus Preclinical Target Identification and Validation Services

Protheragen offers specialized preclinical target identification and validation services to help clients identify and prioritize novel therapeutic targets for keratoconus. Leveraging transcriptomic, proteomic, and genomic analysis techniques, we analyze human keratoconus tissue samples and preclinical models to identify dysregulated genes, proteins, and pathways associated with disease pathogenesis—including collagen degradation, inflammatory responses, oxidative stress, and corneal biomechanical dysfunction. Our services include differential gene expression analysis, protein-protein interaction mapping, and functional validation using in vitro cell models (e.g., human corneal stromal cells) to confirm the role of candidate targets in keratoconus progression. Protheragen also provides target validation through gene silencing, overexpression, and pharmacological modulation, helping clients determine the feasibility of targeting specific pathways to slow or reverse corneal ectasia.

Keratoconus Preclinical Model Development and Characterization Services

Protheragen provides customized preclinical model development and characterization services to support keratoconus drug and therapy evaluation, addressing the critical need for physiologically relevant models of the disease. Our services include the development of in vitro and in vivo models that replicate key keratoconus phenotypes, including collagen hydrogel-based in vitro corneal stromal models with adjustable biomechanical properties, genetic knockout/knock-in mouse models, and chemically induced (e.g., collagenase, ultraviolet radiation) models in mice, rats, and rabbits. Each model is thoroughly characterized using advanced techniques, including Scheimpflug tomography, Brillouin microscopy, transmission electron microscopy (TEM), and biochemical assays to confirm corneal thinning, conical protrusion, reduced collagen fibril density, and dysregulated inflammatory/oxidative stress markers—ensuring alignment with human keratoconus pathology. Protheragen also offers model customization to reflect specific therapeutic targets, enabling clients to evaluate the efficacy of their candidates in relevant disease contexts.

Keratoconus Preclinical Efficacy Evaluation Services

Protheragen delivers comprehensive preclinical efficacy evaluation services to assess the therapeutic potential of drug and therapy candidates for keratoconus. Our efficacy studies are designed to measure key endpoints relevant to disease progression, including changes in corneal thickness, curvature, and biomechanical strength; collagen fibril density and organization; and levels of inflammatory and oxidative stress markers (e.g., IL-6, TNF-α, ROS, NRF2 pathway components). We utilize a range of advanced techniques to evaluate efficacy, including corneal topography/tomography, biomechanical testing (e.g., indentation testing, Brillouin microscopy), histological analysis, and molecular assays (e.g., qPCR, Western blotting, ELISA). For gene and cell therapy candidates, Protheragen provides additional efficacy endpoints, including transgene expression, cell engraftment, and tissue regeneration. All efficacy studies are conducted in compliance with GLP standards, with detailed data analysis and reporting to support regulatory submissions.

Keratoconus Preclinical Safety and Toxicology Evaluation Services

Protheragen offers rigorous preclinical safety and toxicology evaluation services to ensure the safety of keratoconus therapeutic candidates prior to clinical trials. Our services include in vitro and in vivo toxicology studies, focusing on ocular and systemic safety endpoints relevant to ophthalmic therapies. In vitro safety assessments include cytotoxicity testing in human corneal stromal cells, corneal epithelial cells, and other relevant ocular cell types, as well as irritation and corrosion testing using in vitro corneal models. In vivo safety studies are conducted in relevant animal models, evaluating acute and repeat-dose toxicity, local ocular effects (e.g., inflammation, corneal opacity, neovascularization), and systemic toxicity endpoints (e.g., body weight, hematology, clinical chemistry, organ histopathology). Protheragen also provides toxicokinetic and pharmacokinetic (PK) analysis to evaluate drug absorption, distribution, metabolism, and excretion (ADME) in ocular tissues (e.g., cornea, aqueous humor, iris) and systemic circulation, ensuring that therapeutic candidates exhibit favorable safety profiles and PK properties for clinical use.

Keratoconus Preclinical Pharmacokinetic (PK) and Pharmacodynamic (PD) Evaluation Services

Protheragen provides specialized PK and PD evaluation services to optimize the pharmacokinetic properties and therapeutic efficacy of keratoconus drug candidates. Our PK studies focus on measuring drug concentrations in ocular tissues (cornea, aqueous humor, vitreous humor) and systemic fluids (plasma, urine) over time, using sensitive analytical techniques (e.g., LC-MS/MS) to determine key PK parameters such as Cmax, Tmax, AUC, half-life, and tissue distribution. PD studies are designed to correlate drug exposure with therapeutic effects, measuring changes in disease-relevant biomarkers (e.g., collagen synthesis, inflammatory factor levels, corneal biomechanical properties) to establish dose-response relationships. Protheragen's PK/PD services also include formulation optimization, helping clients enhance drug bioavailability, corneal penetration, and sustained release—critical factors for the success of ophthalmic therapies targeting keratoconus. All PK/PD studies are conducted in compliance with regulatory guidelines, providing clients with data to support dosage selection and clinical trial design.

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
• Customized Therapy Development

Disease Models

• Zfp469 BCS/BCS Models
• Ppip5k2 Gene-trap Mouse Models
• UVR Exposure Models
• Eye Rubbing/Scratching Models
• Vitamin A Deficiency Models

Preclinical Research

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

Protheragen prides itself on providing comprehensive preclinical research services that support the development of effective keratoconus therapeutics, including pharmacokinetic and toxicology studies. Employing state-of-the-art laboratory platforms and leveraging profound biological insights, our services are designed to unravel the complexities of keratoconus pathogenesis. If you are interested in our services, please feel free to contact us.

References

• Santodomingo-Rubido Jacinto, et al. "Keratoconus: An updated review." Contact Lens and Anterior Eye 45.3 (2022): 101559.
• Mohammadpour, Mehrdad, Zahra Heidari, and Hassan Hashemi. "Updates on managements for keratoconus." Journal of current ophthalmology 30.2 (2018): 110-124.