- Reducing a key inflammatory pathway protected mice against early macular degeneration like changes
- Removing components of the inflammasome prevented subretinal immune cell invasion and deposit formation
- Work points towards preventive treatments that act before major vision loss occurs
Age related macular degeneration, or AMD, is the leading cause of vision loss and blindness among older adults in the United States.
Current treatments mainly target late stage disease, often once damage is already advanced.
Researchers at the University of Minnesota Medical School wanted to see whether tackling chronic inflammation much earlier in the disease process could protect the retina from AMD like pathology.
Their work, published in Cell Death and Disease, focused on the inflammasome, a protein complex that drives inflammatory responses.
Targeting inflammation in preclinical models
The team used mouse models that develop early features resembling human AMD, including:
- Infiltration of immune cells into the subretinal space
- Formation of basal laminar deposits beneath the retinal pigment epithelium
By genetically removing Nlrp3, a key component of the inflammasome cascade, they were able to see how dampening this pathway affected retinal health over time.
- Eating Greek yoghurt after resistance training lowers inflammation, research finds
- Eating lots of ultra-processed food linked to higher levels of inflammation marker
- Chronic inflammation in ageing not seen across all populations
They found that deleting Nlrp3 protected against hallmark early disease features. Mice lacking this pathway showed:
- Fewer immune cells entering the subretinal space
- Markedly reduced formation of subretinal deposits
Importantly, these protective effects were observed even in ageing mice and in animals carrying an Efemp1 mutation (R345W) linked to basal laminar deposit formation.
No gross structural changes in the retina or retinal pigment epithelium were seen between wild type and mutant animals at twenty months or older, underscoring that the differences lay in subtle pathology rather than obvious anatomical disruption.
Towards preventive therapy for AMD
Associate Professor John Hulleman, senior author on the paper, highlighted the wider implications.
The study suggests that targeting specific aspects of the inflammatory cascade could prevent or delay a spectrum of retinal diseases that resemble early AMD.
Given that AMD currently affects nearly 20 million Americans, an approach that delays progression before severe damage occurs could be life changing for many people.
The next steps for the group include testing whether similar anti inflammatory strategies can not only prevent pathology but also reverse existing disease features once they have emerged.
