Expression of protein kinase CK2 in astroglial cells of normal and neovascularized retina.
We previously documented protein kinase CK2 involvement in retinal neovascularization. Here we describe retinal CK2 expression and combined effects of CK2 inhibitors with the somatostatin analog octreotide in a mouse model of oxygen-induced retinopathy (OIR). CK2 expression in human and rodent retinas with and without retinopathy and in astrocytic and endothelial cultures was examined by immunohistochemistry, Western blotting, and reverse transcriptase-polymerase chain reaction. A combination of CK2 inhibitors, emodin or 4,5,6,7-tetrabromobenzotriazole, with octreotide was injected intraperitoneally from postnatal (P) day P11 to P17 to block mouse OIR. All CK2 subunits (alpha, alpha', beta) were expressed in retina, and a novel CK2alpha splice variant was detected by reverse transcriptase-polymerase chain reaction. CK2 antibodies primarily reacted with retinal astrocytes, and staining was increased around new intraretinal vessels in mouse OIR and rat retinopathy of prematurity, whereas preretinal vessels were negative. Cultured astrocytes showed increased perinuclear CK2 staining compared to endothelial cells. In the OIR model, CK2 mRNA expression increased modestly on P13 but not on P17. Octreotide combined with emodin or 4,5,6,7-tetrabromobenzotriazole blocked mouse retinal neovascularization more efficiently than either compound alone. Based on its retinal localization, CK2 may be considered a new immunohistochemical astrocytic marker, and combination of CK2 inhibitors and octreotide may be a promising future treatment for proliferative retinopathies.
Kramerov
Andrei A
AA
Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, 90048, USA. kramerova@cshs.org
Saghizadeh
Mehrnoosh
M
Pan
Hao
H
Kabosova
Andrea
A
Montenarh
Mathias
M
Ahmed
Khalil
K
Penn
John S
JS
Chan
Candy K
CK
Hinton
David R
DR
Grant
Maria B
MB
Ljubimov
Alexander V
AV
D020533:Angiogenesis Inhibitors; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004338:Drug Combinations; D004642:Emodin / Q000494:pharmacology; D004791:Enzyme Inhibitors; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D012160:Retina / Q000378:metabolism*; D015861:Retinal Neovascularization / Q000378:metabolism*; D012178:Retinopathy of Prematurity / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013004:Somatostatin / Q000031:analogs & derivatives
D020533:Angiogenesis Inhibitors; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D013004:Somatostatin; D047390:Casein Kinase II; D004642:Emodin