Modulation of retinal capillary endothelial cells by Müller glial cell-derived factors.
OBJECTIVE
The inner blood-retinal barrier (BRB) is a gliovascular unit in which macroglial cells surround capillary endothelial cells and regulate retinal capillaries by paracrine interactions. The purpose of the present study was to identify genes of retinal capillary endothelial cells whose expression is modulated by Müller glial cell-derived factors.


METHODS
Conditionally immortalized rat retinal capillary endothelial (TR-iBRB2) and Müller (TR-MUL5) cell lines were chosen as an in vitro model. TR-iBRB2 cells were incubated with conditioned medium of TR-MUL5 (MUL-CM) for 24 h and subjected to microarray and quantitative real-time PCR analysis.


RESULTS
TR-MUL5 cell-derived factors increased alkaline phosphatase activity in TR-iBRB2 cells, indicating that paracrine interactions occurred between TR-iBRB2 and TR-MUL5 cells. Microarray analysis demonstrated that MUL-CM treatment leads to a modulation of several genes including an induction of plasminogen activator inhibitor 1 (PAI-1) and a suppression of an inhibitor of DNA binding 2 (Id2) in TR-iBRB2 cells. Treatment with TGF-beta1, which is incorporated in MUL-CM, also resulted in an induction of PAI-1 and a suppression of Id2 in TR-iBRB2 cells.


CONCLUSIONS
In vitro inner BRB model study revealed that Müller glial cell-derived factors modulate endothelial cell functions including the induction of anti-angiogenic PAI-1 and the suppression of pro-angiogenic Id2. Therefore, Müller cells appear to be one of the modulators of retinal angiogenesis.
Abukawa
Hayato
H
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
Tomi
Masatoshi
M
Kiyokawa
Jumpei
J
Hori
Satoko
S
Kondo
Tetsu
T
Terasaki
Tetsuya
T
Hosoya
Ken-Ichi
K
D000469:Alkaline Phosphatase / Q000378:metabolism; D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D020533:Angiogenesis Inhibitors / Q000037:antagonists & inhibitors; D000818:Animals; D001813:Blood-Retinal Barrier; D002461:Cell Line, Transformed; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000378:metabolism*; D015870:Gene Expression; D051797:Inhibitor of Differentiation Protein 2 / Q000037:antagonists & inhibitors; D046228:Microarray Analysis; D009457:Neuroglia / Q000378:metabolism*; D019899:Paracrine Communication; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000209:etiology / Q000517:prevention & control; D012171:Retinal Vessels / Q000378:metabolism*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism; D015854:Up-Regulation
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; C497451:Id2 protein, rat; D051797:Inhibitor of Differentiation Protein 2; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D000469:Alkaline Phosphatase