Subretinal mononuclear phagocytes induce cone segment loss via IL-1β

Area of Science:

• Ophthalmology
• Immunology
• Cell Biology

Background:

• Cone segments (CS) are vital for daytime vision but degenerate in geographic atrophy (GA) and retinitis pigmentosa (RP).
• The role of subretinal inflammation in cone degeneration in GA and RP remains unclear.
• CD14(+) mononuclear phagocyte (MP) infiltration is observed in the transitional zone (TZ) of GA and in RP.

Purpose of the Study:

• To investigate the role of subretinal MPs in cone segment degeneration in GA.
• To determine the mechanism by which MPs contribute to cone loss.
• To explore therapeutic strategies targeting MPs and IL-1β for vision preservation.

Main Methods:

• Confirmation of CS loss in GA patients' TZ.
• Analysis of subretinal MP infiltration in GA.
• In vitro studies using human and mouse MPs.
• In vivo studies in inflammation-prone Cx3cr1(GFP/GFP) mice.
• Assessment of IL-1β's effect on CS degeneration.

Main Results:

• CS loss was confirmed in the TZ of GA patients, associated with subretinal MP infiltration.
• MP-derived IL-1β was demonstrated to cause severe CS degeneration in vitro and in vivo.
• Subretinal MP accumulation was strongly implicated in photoreceptor pathology in GA and RP.

Conclusions:

• Subretinal MP accumulation and IL-1β production contribute significantly to cone degeneration in GA and RP.
• Targeting subretinal MP accumulation or IL-1β may offer a protective strategy for cone photoreceptors.
• Preserving cone segments could help maintain high-acuity daytime vision in inflammatory retinal diseases like AMD and RP.