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Tmem30a deficiency leads to retinal rod bipolar cell degeneration
Author(s) -
Yang Yeming,
Liu Wenjing,
Sun Kuanxiang,
Jiang Li,
Zhu Xianjun
Publication year - 2019
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14643
Subject(s) - microbiology and biotechnology , outer nuclear layer , retina , glial fibrillary acidic protein , biology , retinal degeneration , outer plexiform layer , retinal , phosphatidylserine , lucifer yellow , programmed cell death , chemistry , apoptosis , biochemistry , neuroscience , immunology , intracellular , immunohistochemistry , phospholipid , membrane , gap junction
Phospholipids are asymmetrically distributed across the mammalian plasma membrane, with phosphatidylserine ( PS ) and phosphatidylethanolamine concentrated in the cytoplasmic leaflet of the membrane bilayer and phosphatidylcholine in the exoplasmic leaflet. This asymmetric distribution is dependent on a group of P4 ATP ases called PS flippases. The proper transport and function of PS flippases require a β‐subunit transmembrane protein 30A ( TMEM 30A). Disruption of PS flippases leads to several human diseases. Tmem30a is essential for photoreceptor survival. However, the roles of Tmem30a in the retinal rod bipolar cells ( RBC ) remain elusive. To investigate the role of Tmem30a in the RBC s, we generated a RBC ‐specific Tmem30a knockout ( cKO ) mouse model using PCP 2‐Cre line. The Tmem30a cKO mice exhibited defect in RBC function and progressive RBC death. PKC α staining of retinal cryosections from cKO mice revealed a remarkable dendritic sprouting of rod bipolar cells during the early degenerative process. Immunostaining analysis of PSD 95 and mG luT6 expression demonstrated that rod bipolar cells in Tmem30a cKO retinas exhibited aberrant dendritic sprouting as a result of impaired synaptic efficacy, which implied a crucial role for Tmem30a in synaptic transmission in the retina. In addition, loss of Tmem30a led to reactive gliosis with increased expression of glial fibrillary acidic protein and CD 68. TUNEL staining suggested that apoptotic cell death occurred in the retinal inner nuclear layer ( INL ). Our data show that loss of Tmem30a in RBC s results in dendritic sprouting of rod bipolar cells, increased astrogliosis and RBC death. Taken together, our studies demonstrate an essential role for Tmem30a in the retinal bipolar cells.Cover Image for this issue: doi: 10.1111/jnc.14492 .