Primary Juvenile Glaucoma (PJG)

Primary juvenile glaucoma (PJG) is a type of primary open-angle glaucoma (POAG) that is seen in young adults and children. At Protheragen, we offer comprehensive services for the development of primary juvenile glaucoma diagnostics and therapeutics.

Overview of Primary Juvenile Glaucoma (PJG)

Primary Juvenile Glaucoma (PJG) is one of the rare types of open-angle glaucoma that is diagnosed in people younger than 40 years. PJG is often associated with raised injury eye pressure (IOP) and progressive optic nerve damage which is quite common. The prevalence of PJG is alarming, especially in South Asian, West Asian, and African men. PJG is usually linked to mutations of MYOCgene(MYOC), which encodes myocilin protein, and also mutations of the CYP1B1 gene which is responsible for the development of the anterior segment of the eye. Such mutations are believed to cause PJG because of the myopia of the outflow pathways, causing further resistance to the path of aqueous outflow, which results in increased eye pressure.

Fig.1 Prevalence of the Observed Inheritance patterns among juvenile-onset open angle glaucoma (JOAG). (Gupta V., et al., 2017)

Diagnostics Development for Primary Juvenile Glaucoma

Molecular diagnostics are fundamental to the detection and therapeutics of Primary Juvenile Glaucoma. It is crucial to conduct genetic tests to screen for mutations on the MYOC and CYP1B1 genes in order to reach the right diagnosis and determine the risk. With more than 250 distinct mutations documented, MYOC mutations are the most frequently associated genetic factor in PJG, which is the most common form of glaucoma. These mutations are frequently associated with the intracellular accumulation of proteins, which leads to decreased myocilin secretion and TM cell apoptosis. On the contrary, CYP1B1 mutations are associated with developmental anomalies at the anterior segment of the eye which also leads to increased intraocular pressure. Early detection of these mutations enables proactive measures to be taken and improving the effectiveness of therapeutics.

Therapeutics Development for Primary Juvenile Glaucoma

• IOP-Lowering Drugs
  The main drug therapy used in PJG cases consists of intraocular pressure (IOP)-lowering drugs. These drug therapies function by either reducing the formation of aqueous humor or raising its outflow. Generally, beta-blockers, carbonic anhydrase inhibitors, and prostaglandin analogs are used. Beta-blockers like timolol block the production of aqueous humor by beta-adrenergic receptors present in the ciliary body. Carbonic anhydrase inhibitors such as dorzolamide block the enzymatic activity of carbonic anhydrase which reduces production of aqueous humor. Prostaglandin analogs, such as latanoprost, increase the outflow of the uveosclera by relaxing the ciliary muscle.
• Gene Therapy Approaches
  There is potential for gene therapy to cure the root genetic mutations of PJG. One strategy consists of correcting the folding and secretion of mutant myocilin proteins using small molecules or molecular chaperones. Trimethylamine N-Oxide (TMAO), for instance, has been shown to improve the correct folding of mutant myocilin by decreasing its intracellular accumulation and reducing endoplasmic reticular (ER) stress. Similarly, sodium 4-phenylbutyrate, another investigational drug, has provided these results in PJG transgenic mouse models.

Our Services

Protheragen is at the forefront of diagnostics and therapeutics development for PJG. We offer preclinical research services, including in vitro and in vivo studies to evaluate the pharmacokinetics and toxicology of novel therapeutics.

Diagnostics Development

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

Therapeutic Development

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

Disease Models

• Spontaneous PJG Models
• Cyp1b1-Deficient Models
• Tyr-Deficient Models
• Angpt1-Deficient or Tek-Deficient Models
• Foxc1-Deficient Zebrafish Models
• Guca1c-Deficient Zebrafish Models

The preclinical development is designed to bridge the gap between basic research and human studies. Protheragen employs a variety of in vitro and in vivo models to evaluate the efficacy and safety of potential therapies. Our team has extensive experience in developing animal models that closely mimic the human condition, allowing us to conduct rigorous testing of novel therapeutic approaches. These models are instrumental in understanding the disease progression and in identifying promising candidates for further development. If you are interested in our services, please feel free to contact us.

References

• Gupta, Viney, et al. "The inheritance of juvenile onset primary open angle glaucoma." Clinical Genetics 92.2 (2017): 134-142.
• Badawi, Abdulrahman H., et al. "Primary congenital glaucoma: An updated review." Saudi Journal of Ophthalmology 33.4 (2019): 382-388.