Melanization and phagocytosis: implications for age related macular degeneration.
Signaling pathways that upregulate melanization in the retinal pigment epithelium (RPE) may also be implicated in the downregulation of rod outer segment (ROS) phagocytosis by the RPE. Melanization activating pathways may also modulate oxygen consumption by the photoreceptors, apolipoprotein E4 levels, and the rate of photoisomerization events such that the net effect may be a reduction in drusen and/or lipofuscin accumulation. An increase in melanin at the apical microvilli of the RPE may shield ROS from light thereby contributing in part to the decrease in the rate of ROS phagocytosis. This decrease in ROS phagocytosis by the RPE may serve to maintain a balance between ingestion and degradation/recycling thereby avoiding an increase to its already substantial metabolic load. Several experimental drugs for age related macular degeneration (ARMD) coincidentally are also capable of decreasing the rate of ROS phagocytosis. This review attempts to identify the signaling pathways that may link the upregulation of melanization to the downregulation of ROS phagocytosis. Phagocytic pathways that are modulated by melanization need to be studied in isolation to determine what role, if any, they possess in ameliorating the onset and progression of ARMD. Many more empirical studies are needed to unravel specific pathways and mechanisms that seem to link melanization with ARMD.
Sarangarajan
Rangaprasad
R
Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences, Worcester, MA, USA. ranga.sarangarajan@wor.mcphs.edu
Apte
Shireesh P
SP
D000818:Animals; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism*; D008543:Melanins / Q000096:biosynthesis*; D010101:Oxygen Consumption; D010587:Phagocytosis / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000378:metabolism; D012374:Rod Cell Outer Segment / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D015854:Up-Regulation
D008543:Melanins