Age and Glaucoma

Although glaucoma is complex and affected by several risk factors, including IOP, family history, and high myopia, age is the most predictive factor. Despite this, the molecular impact of aging on the eye remains limited.

Now, researchers at the University of California have developed a new stress-induced aging mouse model to better understand glaucoma progression (1). The team believes their model offers advantages over previous animal models that do not recapitulate all aspects of glaucoma; for instance, some laboratories focus on developing animal models of chronic IOP elevation whereas others use mice who developed natural mutations. The new model allows researchers to capture the specific time span of molecular changes caused by glaucomatous stress and thus provide a clearer picture of how age and stress directly impact the eye.

Most significantly, the team found that susceptibility to stress is pre-conditioned epigenetically and adapts with age. The researchers also noted that the pathways activated upon exposure to IOP elevation included increased inflammation and cell death, as well as the degradation of extracellular matrix integrity. Moreover, when primed with previous instances of mild IOP elevation, strong stress responses were induced in young tissue upon mild hypertension. Finally, the molecular mechanism of aging was shown to be regulated at the level of chromatin modification, meaning that the rate of aging may be modifiable using drug-affecting enzymes involved in chromatin modifications.

The research team says that the multifaceted results highlight the importance of early diagnosis for managing glaucoma. And outside of glaucoma, the study also suggests a potential use of the retina as a model system for studying molecular and functional changes in aging and neurodegeneration.