EMC3 Is Essential for Retinal Organization and Neurogenesis During Mouse Retinal Development

Abstract

Purpose We used a mouse model to explore the role of the endoplasmic reticulum membrane protein complex subunit 3 (EMC3) in mammalian retinal development. Methods The transcription pattern of Emc3 in C57BL/6 mice was analyzed by in situ hybridization. To explore the effects of EMC3 absence on retinal development, the Cre-loxP system was used to generate retina-specific Emc3 in knockout mice (Emc3 flox/flox , Six3-cre + ; CKO). Morphological changes in the retina of E13.5, E17.5, P0.5, and P7 mice were observed via hematoxylin and eosin staining. Immunofluorescence staining was used to assess protein distribution and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining to assess apoptosis changes. Proteins were identified and quantified by Western blotting and proteomic analysis. Electroretinogram (ERG), fundus color photography, and optical coherence tomography were performed on 5-week-old mice to evaluate retinal function and structure. Results The Emc3 mRNA was widely distributed in the whole retina during development. Loss of retinal EMC3 led to retinal rosette degeneration with mislocalization of cell junction molecules (β-catenin, N-cadherin, and zonula occludens-1) and polarity molecules (Par3 and PKCζ). Endoplasmic reticulum stress and TUNEL apoptosis signals were present in retinal rosette-forming cells. Although the absence of EMC3 promoted the production of photoreceptor cells, 5-week-old mice lost all visual function and had severe retinal morphological degeneration. Conclusions EMC3 regulates retinal structure by maintaining the polarity of retinal progenitor cells and regulating retinal cell apoptosis.

Biomimetic, Injectable, and Self-Healing Hydrogels with Sustained Release of Ranibizumab to Treat Retinal Neovascularization

“…3 months after treatment, the rabbits’ eyes were enucleated after euthanasia and fixed in 10% formalin. Subsequently, 4 μm of paraffin-embedded slices were prepared and then stained with hematoxylin and eosin (HE, Aldrich-Sigma, USA) based on routine procedures . The slides were then examined using an inverted microscope (Olympus, Japan) and reviewed independently by two blinded observers stochastically.…”

The endoplasmic reticulum membrane complex promotes proteostasis of GABAA receptors

“…EMC3 is homologous to known membrane protein insertases Oxa1 family proteins ( Volkmar and Christianson, 2020 ; Wideman, 2015 ), and depletion of EMC3 results in ER stress and activates the unfolded protein response ( Huang et al., 2021 ; Tang et al., 2017 ). Moreover, EMC3 was reported to coordinate the assembly of lipids and proteins required for surfactant synthesis ( Tang et al., 2017 ), maintain differentiation and function of intestinal exocrine secretory lineages ( Huang et al., 2021 ), and play a critical role in mammalian retinal development ( Cao et al., 2021 ; Zhu et al., 2020 ). In parallel, in addition to its role in regulating the biogenesis of acetylcholine receptors in C. elegans ( Richard et al., 2013 ), EMC6 was reported to regulate the autophagosome formation, and knocking down EMC6 impaired autophagy ( Li et al., 2013 ).…”

The Endoplasmic Reticulum Membrane Complex Promotes Proteostasis of GABAAReceptors

“…EMC3 is homologous to known membrane protein insertases Oxa1 family proteins (Volkmar and Christianson, 2020; Wideman, 2015), and depletion of EMC3 results in ER stress and activates the unfolded protein response (Huang et al, 2021; Tang et al, 2017). Moreover, EMC3 was reported to coordinate the assembly of lipids and proteins required for surfactant synthesis (Tang et al , 2017), maintain differentiation and function of intestinal exocrine secretory lineages (Huang et al , 2021), and play a critical role in mammalian retinal development (Cao et al, 2021; Zhu et al, 2020). In parallel, in addition to its role in regulating the biogenesis of acetylcholine receptors in C. elegans (Richard et al , 2013), EMC6 was reported to regulate the autophagosome formation and knocking down EMC6 impaired autophagy (Li et al, 2013).…”