Influence of Growth Differentiation Factor 15 on Intraocular Pressure in Mice

Area of Science:

• Ophthalmology
• Molecular Biology
• Cell Biology

Background:

• Growth Differentiation Factor 15 (GDF15) is a stress-sensitive cytokine implicated in aging and disease.
• Elevated GDF15 is observed in the aqueous humor of glaucoma patients, but its role in intraocular pressure (IOP) and aqueous humor (AH) outflow is unclear.

Purpose of the Study:

• To investigate the role of GDF15 in the regulation of IOP and AH outflow.
• To determine the effects of GDF15 on the trabecular meshwork and conventional AH outflow pathway.

Main Methods:

• Utilized transgenic mice expressing human GDF15 and GDF15 null mice.
• Treated primary human trabecular meshwork cells with recombinant human GDF15 (rhGDF15).
• Assessed IOP, AH outflow facility, and gene expression profiles via RNA-sequencing.

Main Results:

• rhGDF15 increased gene expression related to extracellular matrix, cell adhesion, and chemokine receptors in trabecular meshwork cells.
• Transgenic mice expressing human GDF15 showed significantly increased IOP compared to wild-type controls.
• rhGDF15 perfusion decreased AH outflow facility in enucleated wild-type mouse eyes.

Conclusions:

• GDF15 plays a role in modulating IOP, potentially by decreasing AH outflow through the trabecular pathway.
• These findings suggest GDF15 as a potential factor in glaucoma pathogenesis.
• Further research is warranted to elucidate the precise mechanisms of GDF15 action in the eye.