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Updated: May 8, 2026
Characterization of Vascular Morphology of Neovascular Age-Related Macular Degeneration by Indocyanine Green Angiography
Published on: August 11, 2023
NLRP3 inflammasome blockade inhibits VEGF-A-induced age-related macular degeneration
1Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, MA 02129, USA; Department of Dermatology, Harvard Medical School, Charlestown, MA 02129, USA.
Abstract:
The NLRP3 inflammasome is activated in age-related macular degeneration (AMD), but it remains unknown whether its activation contributes to AMD pathologies. VEGF-A is increased in neovascular ("wet") AMD, but it is not known whether it plays a role in inflammasome activation, whether an increase of VEGF-A by itself is sufficient to cause neovascular AMD and whether it can contribute to nonexudative ("dry") AMD that often co-occurs with the neovascular form. Here, it is shown that an increase in VEGF-A results in NLRP3 inflammasome activation and is sufficient to cause both forms of AMD pathologies. Targeting NLRP3 or the inflammasome effector cytokine IL-1β inhibits but does not prevent VEGF-A-induced AMD pathologies, whereas targeting IL-18 promotes AMD. Thus, increased VEGF-A provides a unifying pathomechanism for both forms of AMD; combining therapeutic inhibition of both VEGF-A and IL-1β or the NLRP3 inflammasome is therefore likely to suppress both forms of AMD.
Insights
Increased vascular endothelial growth factor-A (VEGF-A) activates the NLRP3 inflammasome, causing both dry and wet age-related macular degeneration (AMD). Targeting VEGF-A and IL-1β may suppress both AMD forms.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- The NLRP3 inflammasome is implicated in age-related macular degeneration (AMD).
- The role of vascular endothelial growth factor-A (VEGF-A) in inflammasome activation and AMD pathogenesis is unclear.
- VEGF-A is elevated in wet AMD, but its contribution to dry AMD is unknown.
Purpose of the Study:
- To investigate if VEGF-A increase causes NLRP3 inflammasome activation.
- To determine if VEGF-A is sufficient to induce both dry and wet AMD pathologies.
- To explore therapeutic strategies targeting VEGF-A, NLRP3, IL-1β, and IL-18 for AMD.
Main Methods:
- Investigated the link between VEGF-A levels and NLRP3 inflammasome activation.
- Assessed the sufficiency of VEGF-A increase in causing AMD pathologies in a model.
- Evaluated the effects of targeting NLRP3, IL-1β, and IL-18 on VEGF-A-induced AMD.
Main Results:
- Increased VEGF-A activates the NLRP3 inflammasome.
- Elevated VEGF-A is sufficient to cause both dry and wet AMD pathologies.
- Targeting NLRP3 or IL-1β partially inhibited VEGF-A-induced AMD, while IL-18 targeting exacerbated it.
Conclusions:
- Increased VEGF-A represents a unifying pathomechanism for both dry and wet AMD.
- Combined therapeutic inhibition of VEGF-A and IL-1β or NLRP3 may effectively suppress both forms of AMD.
- Targeting IL-18 is not a viable therapeutic strategy for AMD.
