Description
Scientific Abstract
Background – Glaucoma affects more than 60 million people worldwide and is a leading cause of irreversible blindness. While elevated intraocular pressure (IOP) is the primary modifiable risk factor for glaucoma, degeneration of retinal ganglion cell (RGC) continues even after IOP is reduced.This continued apoptosis of RGC is a shared pathway in glaucoma, retinal ischemia, and optic nerve injury. Citicoline, an endogenous mononucleotide derived from choline, has demonstrated neuroprotective effects on RGC morpho-functional integrity. It also has been shown citicoline slows down visual function decline in patients, through an IOP-independent pathway. However, whether this is through its neuroprotective or regenerative effect of damaged optic nerve remains unclear.
Methods- Unilateral optic nerve crush (ONC) was performed on the right eye adult C57BL/6J mice aged 9 weeks. Animals were randomly allocated to either the control group (n=5) or the citicoline treatment group(n=5). The animals in the treatment group received daily intraperitoneal citicoline injections (500 mg/kg), while the animals in the control group received daily saline solution, for 7 days. Intravitreal injections of cholera toxin subunit B (CTB)-555 (1 µL) were performed on all animals two days before tissue collection to assess axonal regeneration.
Results-CTB fluorescence was detected in all animals, however, the signal intensity was variable, indicating inconsistency in intravitreal injections. A distinct crush site was identifiable in only two animals, limiting the ability to reliably assess axonal regeneration. No evidence of axonal regeneration beyond the crush site was observed in either group.
Lay Abstract
Lay Abstract:
Glaucoma is one of the leading causes of permanent blindness affecting millions of people worldwide. So far, the most common treatment for glaucoma is to reduce intraocular pressure (IOP), the pressure inside the eye. However, vision decline continues even after IOP reduction, which presents as a challenge for treatment. Citicoline, a naturally occurring compound in the body, has shown positive results in improving glaucoma in an IOP-independent pathway. However, the underlying mechanism of whether citicoline’s effect is via neuroprotection or regeneration of the damaged nerves remains unknown. In this study, we investigated this using a glaucoma mouse model. After damaging the optic nerve in one eye, we labelled the axons to track if any nerves were able to grow when treated with citicoline. Understanding the mechanism by which this works would provide insights in clinical application relevant to treating axonal damage in optic neuropathies like glaucoma and develop a framework to test other candidate drugs.
| Lay Title | Optic nerve regeneration with citicoline treatment |
|---|---|
| Role | Other |