Changes in melatonin receptor expression in a murine model of glaucoma

Area of Science:

• Ophthalmology
• Neuroscience
• Pharmacology

Background:

• Glaucoma is a leading cause of irreversible blindness.
• Melatoninergic receptors regulate intraocular pressure (IOP) by influencing aqueous humor production.
• The role of melatonin receptors in glaucoma pathogenesis is not fully understood.

Purpose of the Study:

• To investigate changes in melatoninergic receptor expression during glaucoma development in DBA/2J mice.
• To compare receptor expression in glaucomatous DBA/2J mice with control C57BL/6J mice.
• To explore the therapeutic potential of melatonin and its analogs in modulating IOP in glaucoma.

Main Methods:

• Quantitative real-time PCR to measure mRNA expression of MT1, MT2, and GPR50 receptors.
• Immunohistochemical analysis of receptor expression in ciliary processes.
• In vivo assessment of IOP changes following topical administration of melatonin, its analog (5-MCA-NAT), and MT2 antagonist (4PPDOT).

Main Results:

• Melatonin receptor expression, especially MT2, significantly decreased in DBA/2J mice with developing glaucoma.
• Receptor expression remained stable in age-matched C57BL/6J control mice.
• MT2 receptor antagonism with 4PPDOT showed a more pronounced IOP-lowering effect in DBA/2J mice, suggesting its correlation with glaucoma.

Conclusions:

• Glaucoma development is associated with a decay in melatonin receptor expression, impairing the natural IOP-lowering function of melatonin.
• Exogenous administration of melatonin or its analogs can potentially activate remaining receptors to counteract IOP elevation.
• Targeting MT2 receptors may offer a therapeutic strategy for managing glaucoma.