Crumbs proteins regulate layered retinal vascular development required for vision |
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Affiliation: | 1. Department of Ophthalmology, Yeungnam University College of Medicine, Daegu, Republic of Korea;2. Department of Neurology, Kyungpook National University Hospital, Daegu, Republic of Korea;1. Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland;2. Department of Ophthalmology, Eye Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA;1. Department of Bioscience, Biotechnologies and Biopharmaceutics and Centre of Excellence in Comparative Genomics, University of Bari “Aldo Moro”, 70126 Bari, Italy;2. Department of Neuroscience, Albert Einstein College of Medicine, New York, Bronx, NY, USA;3. IRCCS “Casa Sollievo della Sofferenza”, Research Hospital, San Giovanni Rotondo, Italy;4. Department of Biology, University of Pisa, 56127 Pisa, Italy;5. School of Medicine, Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari “Aldo Moro”, 70126 Bari, Italy;6. Institute of Biomembranes and Bioenergetics, National Research Council, Via Amendola 165/A, 70126 Bari, Italy;7. National Institute of Biostructures and Biosystems (INBB), Viale Medaglie D''Oro 305, 00136 Rome, Italy |
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Abstract: | Crumbs proteins are transmembrane proteins that regulate cellular apico-basal polarity. Animals carrying mutated crb1 present retinal vascular abnormalities; this mutation is associated with progressive retinal degeneration with intraretinal cystoid fluid collection in humans. This study aimed to evaluate a potential role of crumbs proteins in retinal vascular development and maintenance. We demonstrated that crumbs homologues (CRBs) were differentially expressed and changed dramatically during mouse retinal vascular development. Intravitreal injection of CRB1 and CRB2 siRNA induced delayed development of the deep capillary plexus and premature development of the intermediate capillary plexus, resulting in disrupted vascular integrity. However, microfluidic chip assay using human retinal endothelial cells revealed that CRBs do not directly affect in vitro retinal angiogenesis. CRBs control retinal angiogenesis by regulating neuroglial vascular endothelial growth factor-A (VEGFA) and matrix metalloproteinase-3 expression. These findings demonstrate a pivotal role of CRBs in providing critical neurotrophic support through normal layered vascular network development and maintenance. This implies that preserving CRBs and restoring layered retinal vascular networks could be novel targets for preventing vision-threatening retinal diseases. |
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Keywords: | Crumbs protein Retina. angiogenesis Deep vascular complex Müller glia cell SCP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0035" }," $$" :[{" #name" :" text" ," _" :" superficial capillary plexus DCP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0045" }," $$" :[{" #name" :" text" ," _" :" deep capillary plexus ICP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0055" }," $$" :[{" #name" :" text" ," _" :" intermediate capillary plexus VEGF" },{" #name" :" keyword" ," $" :{" id" :" kwrd0065" }," $$" :[{" #name" :" text" ," _" :" vascular endothelial growth factor RP" },{" #name" :" keyword" ," $" :{" id" :" kwrd0075" }," $$" :[{" #name" :" text" ," _" :" retinitis pigmentosa DVC" },{" #name" :" keyword" ," $" :{" id" :" kwrd0085" }," $$" :[{" #name" :" text" ," _" :" deep vascular complex |
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