Autophagy in the Aging and Experimental Ocular Hypertensive Mouse Model.

Area of Science:

• Ocular biology
• Neuroscience
• Cellular biology

Background:

• Aging is associated with increased risk of ocular diseases, including glaucoma.
• Autophagy, a cellular degradation process, plays a critical role in maintaining cellular homeostasis.
• Dysregulation of autophagy has been implicated in various age-related neurodegenerative disorders.

Purpose of the Study:

• To investigate the role of autophagy in the outflow pathway and retinal ganglion cell layer in aging and ocular hypertensive mouse models.
• To determine how aging affects autophagy in the context of elevated intraocular pressure (IOP).

Main Methods:

• Ocular hypertension was induced in young (4-month-old) and aged (18-month-old) C57BL/6J and GFP-LC3 mice via limbal vein injection.
• Intraocular pressure (IOP) was monitored weekly.
• Autophagy markers (LC3B, Lamp1, p62) were assessed using western blot and immunofluorescence.
• Retinal ganglion cell (RGC) and optic nerve axon counts were performed.

Main Results:

• Aged mice developed sustained elevated IOP, unlike younger mice.
• Transgenic GFP-LC3 mice showed a higher incidence and magnitude of IOP elevation.
• Autophagy was dysregulated in aged hypertensive eyes, with the LC3-II/LC3-I ratio correlating with IOP.
• Aging exacerbated RGC and axon loss in hypertensive eyes, with autophagic structures observed in degenerating axons.

Conclusions:

• Autophagy is dysregulated in the trabecular meshwork and retinal tissues with aging.
• This age-related autophagy dysfunction contributes to neurodegeneration in glaucoma.