Antenatal IL-1-dependent inflammation persists postnatally and causes retinal and sub-retinal vasculopathy in progeny

Area of Science:

• Ocular development
• Inflammation research
• Perinatal medicine

Background:

• Antenatal inflammation, such as chorioamnionitis, negatively impacts fetal organ development, including the eyes.
• Interleukin-1 beta (IL-1β) is implicated in hyperoxia-induced retinopathy, but its role in preterm birth-associated retinal vasculopathy is unclear.

Purpose of the Study:

• To investigate the specific role of antenatal IL-1β in retinal and choroidal vascular development following preterm birth (PTB) independent of hyperoxia.
• To evaluate the efficacy of IL-1 receptor (IL-1R) antagonists in preventing IL-1β-induced ocular damage.

Main Methods:

• A murine model was used to induce PTB via in utero IL-1β injection.
• Retinal and choroidal vascular development was assessed postnatally.
• The therapeutic effects of IL-1R antagonists (101.10 and Kineret) were evaluated.

Main Results:

• IL-1β exposure led to elevated pro-inflammatory genes and sustained inflammatory cell infiltration in fetal eyes.
• This resulted in delayed retinal vessel growth, choroidal thinning, and long-term retinal damage.
• Antenatal administration of IL-1R antagonists, particularly 101.10, effectively prevented these adverse inflammatory and vascular outcomes.

Conclusions:

• Antenatal IL-1β plays a critical role in causing persistent ocular inflammation and perinatal vascular eye injury associated with PTB.
• Antenatal treatment with the IL-1R modulator 101.10 shows significant promise in preventing these detrimental effects.