609 © Springer International Publishing AG, part of Springer Nature 2018 J. D. Ash et al. (eds.), Retinal Degenerative Diseases, Advances in Experimental Medicine and Biology 891, https://doi.org/10.1007/978-3-319-75402-4_74 Chapter 74 Microtubule-Associated Protein 1 Light Chain 3 (LC3) Isoforms in RPE and Retina Anuradha Dhingra, Desiree Alexander, Juan Reyes-Reveles, Rachel Sharp, and Kathleen Boesze-Battaglia Abstract Microtubule-associated protein 1 light chain 3 (MAP1LC3), a human homologue of yeast Atg8, is an essential component of autophagy. LC3 plays a criti- cal role in hybrid degradation pathways in which some but not all components of autophagy are coupled with phagocytosis in a process known as LC3-associated phagocytosis (LAP). LC3 exists as three highly homologous isoforms in human (LC3A, LC3B, and LC3C) with two of these (LC3A and LC3B) in mouse. LC3B predominated in both fetal and adult human retinal pigment epithelium (RPE) rela- tive to LC3A and LC3C, while in mouse RPE and neural retina, LC3A and LC3B were expressed at approximately equivalent levels. In situ hybridization studies localized LC3A and LC3B transcripts in the retina and RPE. LC3B protein was detected in C57Bl6/J RPE and retinal lysates and was absent in the LC3BKO mouse. Keywords LC3 isoforms · Phagocytosis · Retinal pigment epithelium 74.1 Introduction Autophagy proteins are strongly expressed in the retina and in the RPE, with accu- mulation of proteins and damaged organelles a common characteristic of the aging RPE as well as of age-related macular degeneration (Mitter et al. 2012; Rodriguez- Muela et al. 2013; Boya et al. 2016; Kauppinen et al. 2016; Szatmari-Toth et al. 2016). In addition to macroautophagy, the catabolic cell survival mechanism, nor- mal vision is also dependent on a hybrid autophagy-phagocytosis degradative path- way termed LC3-associated phagocytosis (LAP) (Kim et al. 2013; Frost et al. 2015; Martinez et al. 2015). LAP plays a critical role in visual pigment regeneration (Kim et al. 2013) as well as the complete degradation of phagosomes (Frost et al. 2015). LAP and autophagy both rely on the lipidation of LC3 to LC3II which enables its A. Dhingra · D. Alexander · J. Reyes-Reveles · R. Sharp · K. Boesze-Battaglia (*) Department of Biochemistry, SDM, University of Pennsylvania, Philadelphia, PA, USA e-mail: battagli@upenn.edu