Study of LRP1 in cellular inflammatory component during choroidal neovascularization

TOVO, A.; SUBIRADA, PAULA V.; VAGLIENTI, MARIA V.; LUNA PINTO, JD; SÁNCHEZ, MARÍA C.; CHIABRANDO, GA.; BARCELONA, PABLO F.

Mar del Plata

Congreso; LXVII ANNUAL MEETING OF SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2022

REUNIÓN CONJUNTA SAIC SAI&FAIC SAFIS 2022

Age-related macular degeneration (AMD) in its Choroidal Neovascularization(CNV) stage is the leading cause of vision loss amongadults. Mononuclear phagocytic cells (MPC), such as resident microglia and monocyte-derived macrophages, collaborate in establisha chronic inflammatory state that can lead to the onset of CNV.The multi-ligand receptor Low Density Lipoprotein Receptor-RelatedProtein 1 (LRP1), is a ligand-dependent anti-inflammatory factor expressedin the cell inflammatory component, including macrophagesand microglia. However, the role of LRP1 in CNV is not establishedyet. In the present study we aim to characterize the LRP1 levelsand localization during CNV progression in a mouse model of CNV.C57BL/6 adult mice were treated with four spots of argon green laserphotocoagulation per eye. At 1, 4, 7, 14 and 21 days after laser, micewere sacrificed and choroid tissue was processed by Western Blotto study LRP1 protein levels. At 4 days after laser, TNFα and LRP1transcript levels were analyzed by qRT PCR and LRP1 expressionin peripheral blood monocytes and MPC from choroids tissue wereevaluated by FACS assays. All experiments were compared withcontrol animals without laser. We could observe on choroid tissuefrom CNV animals increased levels of LRP1 at 1 and 4 days afterlaser. At 4 days after laser, the mRNA levels of pro-inflammatory cytokine,TNFα, were increased. In addition, the number of peripheralblood monocytes and their LRP1 expression were increased in CNVmice respect to control. However, LRP1 mRNA levels was unmodifiedon choroid. In conclusion, we observed increased LRP1 levelsin early stages of CNV progression associated with enhanced proinflammatory cytokine expressions, which was reverted after 4 days.These results suggest that the increased levels of LRP1 in CNV isdue to MPC infiltration from circulating monocytes and resident microglialcells. Further studies are needed to determinate the role ofLRP1 on these cells during CNV.