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Published on: September 26, 2015
Expression of protein kinase CK2 in astroglial cells of normal and neovascularized retina
Andrei A Kramerov1, Mehrnoosh Saghizadeh, Hao Pan
1Ophthalmology Research Laboratories, Cedars-Sinai Medical Center, University of California at Los Angeles School of Medicine, 90048, USA. kramerova@cshs.org
Abstract:
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.
Insights
Protein kinase CK2 is involved in retinal neovascularization. Combining CK2 inhibitors with octreotide effectively blocked this process in a mouse model, suggesting a potential treatment for proliferative retinopathies.
Area of Science:
- Ophthalmology
- Molecular Biology
- Pharmacology
Background:
- Protein kinase CK2 (CK2) has been implicated in retinal neovascularization.
- Understanding CK2 expression patterns and therapeutic interventions is crucial for treating retinopathy.
Purpose of the Study:
- To investigate retinal CK2 expression in various models of retinopathy.
- To evaluate the combined therapeutic effects of CK2 inhibitors and octreotide in a mouse model of oxygen-induced retinopathy (OIR).
Main Methods:
- Immunohistochemistry, Western blotting, and RT-PCR were used to examine CK2 expression in human and rodent retinas and cell cultures.
- A mouse OIR model was treated with CK2 inhibitors (emodin or TBB) combined with octreotide.
- CK2 subunit expression, localization, and mRNA levels were analyzed.
Main Results:
- All CK2 subunits (alpha, alpha', beta) were expressed in the retina, with a novel splice variant detected.
- CK2 staining was prominent in retinal astrocytes and increased around neovascular vessels in OIR.
- Combined treatment with CK2 inhibitors and octreotide significantly blocked retinal neovascularization more effectively than monotherapy.
Conclusions:
- CK2 is localized to retinal astrocytes and can serve as an immunohistochemical marker.
- The combination of CK2 inhibitors and octreotide shows promise as a future therapeutic strategy for proliferative retinopathies.
