Introduction of Chronic Ocular Hypertension Models in Non-Human Primate (NHP)

Glaucoma is one of the most common causes of irreversible blindness worldwide. Although the pathophysiology of retinal ganglion cell loss is not fully understood, intraocular pressure (IOP) is a major risk factor, and clinical trials have shown that lowering IOP is an effective treatment modality. Non-human primates (NHPs) are homologous to humans and share anatomical structures and physiological functions consistent with the human eye, making nonhuman primates an excellent model for studying ocular pathology. NHP models of chronic ocular hypertension (COHT) include steroid-induced glaucoma, intracameral microbead-induced glaucoma, and laser photocoagulation-induced glaucoma. Compared with Dex-induced and microbead-induced glaucoma, laser photocoagulation COHT is superior with the advantages of non-invasiveness, mild inflammatory response, and long-term high intraocular pressure. Therefore, the laser photocoagulation COHT model in nonhuman primates is an ideal model for researchers to develop long-acting anti-glaucoma drugs.

Fig. 1. Methods of laser-induced chronic ocular hypertension (COHT) model. (Sun D, et al., 2022)

Service Overview

Ace Therapeutics is a supplier of comprehensive ocular disease models. With our in-depth understanding of non-human primates, we provide you with a non-human primate model of chronic ocular hypertension here.

This model closely mimics the state of open-angle glaucoma, involving chronic and progressive elevations in intraocular pressure and subsequent damage to the retinal nerve fiber layer, through disruption of the trabecular meshwork. You can choose this model to study the relationship between intraocular pressure (IOP) and loss of retinal nerve fiber layer (RNFL) thickness or to test the effectiveness and safety of potential anti-glaucoma drugs (lowering IOP) and optic neuroprotective drugs to treat glaucoma in humans.

Explore Ace Therapeutics' Non-Human Primate (NHP) Models of Laser-Induced Chronic Ocular Hypertension

Ace Therapeutics' experienced scientists have successfully established a chronic ocular hypertension model by destroying the trabecular meshwork in Rhesus monkeys with laser photocoagulation.

• Protocol for Laser-Induced Chronic Ocular Hypertension Model in Non-Human Primate (NHP)

• Ophthalmic examination before modeling, including tonometry, slit-lamp biomicroscopy, pachymetry, disc photography, and OCT measurement of RNFL thickness before laser photocoagulation to rule out the influence of any existing ocular disease.
• Anesthesia and ocular treatment, including deep general anesthesia by intramuscular injection, topical pilocarpine nitrate eye drops for pupil constriction, and topical oxybucaine hydrochloride eye drops for topical anesthesia.
• For laser photocoagulation: The TX532 laser photocoagulation instrument was used to all-around photocoagulate the Rhesus monkeys' entire middle trabecular meshwork in a dark room to form about 200 continuous and non-overlapping light spots.  

Laser parameters: 50 µm spot size, 0.1-0.5 s duration, and 800-1,000 mW laser power.

• Postoperative treatment: topical antibiotics to reduce non-infectious inflammation after laser photocoagulation.
• Monitor intraocular pressure changes, and judge whether to continue photocoagulation according to intraocular pressure until a stable high intraocular pressure is obtained.
• Repeat photocoagulation 2-4 times (optional step).

• Protocol for Testing the Efficacy of Anti-Glaucoma Drugs

Given our unparalleled experience in ophthalmic pharmacology, our ophthalmic pharmacologists also develop a standardized protocol for intracameral injection in nonhuman primates to verify the reliability of the model and test the efficacy of anti-glaucoma drugs.

• Slit-lamp biomicroscopy.
• Deep anesthesia.
• Antibiotics were used to prevent eye infections during preoperative.
• Intracameral injections of drugs.
• Antibiotic eye ointment was used to prevent eye infections after surgery.

Available Support Services

In order to accurately characterize the biological functions of chronic ocular hypertension Rhesus monkeys, our researchers perform endpoint assessments through the following analytical tools, including but not limited to:

• Tonometry.
• Slit lamp biomicroscopy.
• Optical Coherence Tomography (OCT).

Central corneal thickness.

Retinal nerve fiber layer (RNFL) thickness.

Macular ganglion cell layer (GCL) thickness.

Ganglion cell-inner plexiform layer (GCIPL) thickness.

• Histological analysis.
• Immunohistochemical analysis.

Ace Therapeutics aims to provide a valuable tool to help our global customers explore the molecular mechanism of glaucoma and develop promising therapies. If you are interested in our services or need more detailed information, please feel free to contact us. Our experienced scientists are ready to help you!

References

1. Sun D, Wang B, Yang Z, et al. Protocol for laser-induced chronic ocular hypertension and intracameral injection in nonhuman primates. STAR Protoc. 2022, 3(4):101801.
2. Tu S, Li K, Ding X, et al. TonoVet versus Tonopen in a high intraocular pressure monkey model. Mol Vis. 2019, 25:391-399.
3. Tu S, Li K, Ding X, et al. Relationship between intraocular pressure and retinal nerve fibre thickness loss in a monkey model of chronic ocular hypertension. Eye (Lond). 2019, 33(12):1833-1841.

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