Optic nerve damage in mice with a targeted type I collagen mutation

Area of Science:

• Ophthalmology
• Genetics
• Neuroscience

Background:

• Transgenic Col1a1(r/r) mice exhibit a gradual increase in intraocular pressure (IOP) with open angles.
• This genetic modification provides a model for studying conditions associated with elevated IOP.

Purpose of the Study:

• To investigate and quantify optic nerve axonal loss in transgenic Col1a1(r/r) mice over time.
• To establish a correlation between sustained elevated IOP and neurodegeneration in the optic nerve.

Main Methods:

• Intraocular pressure (IOP) was measured in transgenic Col1a1(r/r) and control wild-type mice at multiple age points (7-54 weeks) using a microneedle method.
• Optic nerves were analyzed via electron microscopy at 24 and 54 weeks to determine axonal density and total axonal number.
• Axonal counts were performed on masked, systematically collected cross-sections posterior to the globe.

Main Results:

• Transgenic mice demonstrated significantly higher IOP compared to controls from 16 weeks onwards.
• A significant reduction in mean axonal density and total axonal number was observed in transgenic mice at 54 weeks compared to controls and to younger transgenic mice.
• Mean axonal loss in transgenic mice between 24 and 54 weeks was approximately 28.7%.

Conclusions:

• Transgenic Col1a1(r/r) mice exhibit sustained elevated IOP and progressive optic nerve axon loss.
• These mice represent a valuable model for primary open-angle glaucoma research.
• The model facilitates the study of the relationship between collagen type I metabolism and optic nerve damage.