Muller Cell Regulated Microglial Activation and Migration in Rats With N-Methyl-N-Nitrosourea-lnduced Retinal Degeneration

被引：17

作者：

Zhang, Shuai ^{[1
]}

Zhang, Shanshan ^{[1
]}

Gong, Wenqing ^{[1
]}

Zhu, Guopei ^{[2
]}

Wang, Songtao ^{[1
]}

Wang, Yalin ^{[3
]}

Halim, Michael ^{[1
]}

Wang, Kaidi ^{[4
]}

Zhou, Guomin ^{[5
]}

Liu, Qiong ^{[1
,5
]}

机构：

[1] Fudan Univ, Sch Basic Med Sci, Dept Anat Histol & Embryol, Shanghai, Peoples R China

[2] Sch Basic Med Sci, Dept Integrat Med & Neurobiol, Shanghai, Peoples R China

[3] Fudan Univ, Eye & ENT Hosp, Shanghai Med Coll, Shanghai, Peoples R China

[4] Shanghai Jiao Tong Univ, Sch Med, Dept Radiat Oncol, Shanghai Peoples Hosp 9, Shanghai, Peoples R China

[5] Key Lab Med Imaging Comp & Comp Assisted Interven, Shanghai, Peoples R China

来源：

FRONTIERS IN NEUROSCIENCE | 2018年 / 12卷

基金：

中国国家自然科学基金;

关键词：

retinitis pigmentosa; microglia; N-methyl-N-nitrosourea; Muller cells; crosstalk; PHOTORECEPTOR; DEATH; MECHANISMS; APOPTOSIS; TARGET; BRAIN; GLIA; RD;

D O I：

10.3389/fnins.2018.00890

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

During the pathogenesis of retinitis pigmentosa (RP), the roles of retinal microglial cells after activation have not been fully elucidated. Herein, experimental RP was induced in Sprague Dawley rats by intraperitoneal injection of N-methyl-N-nitrosourea (MNU) at 50 mg/kg, and the effects of MNU on the retinas were evaluated, respectively, by retinal histology and electroretinography recordings at serial time points. Time-dependent and gradual loss of photoreceptor cells, disrupted arrangement of the outer nuclear layer (ONL), and significant reductions in both a-wave and b-wave amplitudes were observed. Morphology changes were observed in retinal microglial cells; meanwhile, with time, the number of lba1-positive microglia and their infiltration into the ONL gradually increased. Furthermore, physical interaction of microglial-Muller cell processes following microglial activation was observed after MNU injection. In addition, Muller cells increased CX3CL1 secretion, enhanced microglial cell migration, and upregulated the CX3CR1 expression of the latter. Our observations implied that, during the pathogenesis of RP by MNU, microglial cells exhibit a prominent morphology change and Muller cells can induce activated microglia infiltration by increasing secretion of the chemotaxis factor, CX3CL1, and promoting the migration of retinal microglial cells. This novel finding highlights a potential therapeutic target aimed at regulating the microglial response.

引用

页数：8

共 37 条

[1] MICROGLIAL ACTIVATION IN THE INJURED AND HEALTHY BRAIN: WHAT ARE WE REALLY TALKING ABOUT? PRACTICAL AND THEORETICAL ISSUES ASSOCIATED WITH THE MEASUREMENT OF CHANGES IN MICROGLIAL MORPHOLOGY [J].

Beynon, S. B. ;

Walker, F. R. .

NEUROSCIENCE, 2012, 225 :162-171

[2] Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism [J].

Block, ML ;

Hong, JS .

PROGRESS IN NEUROBIOLOGY, 2005, 76 (02) :77-98

[3] Loss of photic entrainment at low illuminances in rats with acute photoreceptor degeneration [J].

Boudard, Domitille L. ;

Mendoza, Jorge ;

Hicks, David .

EUROPEAN JOURNAL OF NEUROSCIENCE, 2009, 30 (08) :1527-1536

[4] APOPTOSIS - FINAL COMMON PATHWAY OF PHOTORECEPTOR DEATH IN RD, RDS, AND RHODOPSIN MUTANT MICE [J].

CHANG, GQ ;

HAO, Y ;

WONG, F .

NEURON, 1993, 11 (04) :595-605

[5] Distribution, markers, and functions of retinal microglia [J].

Chen, L ;

Yang, PZ ;

Kijlstra, A .

OCULAR IMMUNOLOGY AND INFLAMMATION, 2002, 10 (01) :27-39

[6] AAV Mediated GDNF Secretion From Retinal Glia Slows Down Retinal Degeneration in a Rat Model of Retinitis Pigmentosa [J].

Dalkara, Deniz ;

Kolstad, Kathleen D. ;

Guerin, Karen I. ;

Hoffmann, Natalie V. ;

Visel, Meike ;

Klimczak, Ryan R. ;

Schaffer, David V. ;

Flannery, John G. .

MOLECULAR THERAPY, 2011, 19 (09) :1602-1608

[7] Activation of multiple pathways during photoreceptor apoptosis in the rd mouse [J].

Doonan, F ;

Donovan, M ;

Cotter, TG .

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2005, 46 (10) :3530-3538

[8] Astrocytes and Muller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa [J].

Fernandez-Sanchez, Laura ;

Lax, Pedro ;

Campello, Laura ;

Pinilla, Isabel ;

Cuenca, Nicolas .

FRONTIERS IN CELLULAR NEUROSCIENCE, 2015, 9

[9] Alternatively activated microglia and macrophages in the central nervous system [J].

Franco, Rafael ;

Fernandez-Suarez, Diana .

PROGRESS IN NEUROBIOLOGY, 2015, 131 :65-86

[10] A role of Heat Shock Protein 70 in Photoreceptor Cell Death: Potential as a Novel Therapeutic Target in Retinal Degeneration [J].

Furukawa, Ayako ;

Koriyama, Yoshiki .

CNS NEUROSCIENCE & THERAPEUTICS, 2016, 22 (01) :7-14

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