Diverse Regulation of Retinal Pigment Epithelium Phagocytosis of Photoreceptor Outer Segments by Calcium-Independent Phospholipase A₂, Group VIA and Secretory Phospholipase A₂, Group IB

Abstract

Purpose: To investigate the roles of the phospholipases A₂ (PLA₂) subtypes, iPLA₂-VIA and sPLA₂-IB in retinal pigment epithelium (RPE) phagocytosis of photoreceptor outer segments (POS) and to explore a possible interaction between sPLA₂-IB and iPLA₂-VIA in the RPE.

Methods: To explore the role of iPLA₂-VIA in RPE phagocytosis of POS, experiments with iPLA₂-VIA vector transfection, iPLA₂-VIA^−/− knockout (KO) mice, and iPLA₂-VIA inhibition by bromoenol lactone (BEL) were done. Exogenous addition of sPLA₂-IB was used to investigate the role of sPLA₂-IB in RPE phagocytosis. A Luciferase Reporter Vector containing the iPLA₂-VIA promoter was used to study the effects of sPLA₂-IB on the iPLA₂-VIA promoter.

Results: ARPE-19 and primary mouse RPE cells transfected with iPLA₂-VIA showed increased phagocytosis. Phagocytosis was reduced in primary mouse RPE inhibited with BEL and in RPE from KO mice. Exogenous addition of enzymatically active and inactive sPLA₂-IB reduced phagocytosis in ARPE-19 and primary mouse RPE cells. Finally, sPLA₂-IB did not seem to affect the iPLA₂-VIA promoter.

Conclusion: The present study confirms the involvement of iPLA₂-VIA in efficient RPE phagocytosis of POS, while exogenously added sPLA₂-IB decreases phagocytosis regardless of enzymatic activity. No apparent interaction between iPLA₂-VIA and sPLA₂-IB was found.

KEYWORDS::

• Phagocytosis
• Group VIA phospholipase A₂
• Group IB phospholipases A₂
• Retinal pigment epithelium
• Photoreceptor outer segments

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.