Expression of Protein Kinase CK2 in the Retina and Retinal Neovascularization

Abstract

Abstract: : Purpose: Our previous data implicated protein kinase CK2 (formerly, casein kinase 2) in retinal angiogenesis that is abnormal in proliferative diabetic retinopathy (DR). The purpose was to study CK2 subunit expression in normal and diabetic retinas and in rodent models of proliferative retinopathy. Methods: mRNA levels of CK2 α, α' and ß subunits were identified by quantitative RT–PCR (QPCR). CK2 subunit expression in retinas was studied by Western blotting and immunohistochemistry. A potent CK2 inhibitor, emodin (30mg/kg/day), was used in a mouse model of oxygen–induced retinopathy in combination with somatostatin analog, octreotide (1mg/kg/day), intraperitoneally, twice daily from P11 to P17. Numbers of preretinal nuclei in 10 paraffin sections per eye were compared to vehicle–injected controls. Results: The expression of all subunits was decreased in DR retinas by QPCR. The most abundant α subunit splice variant was variant 2 with exons 1, 3, 4. By Western blotting, however, similar levels of CK2 were found in normal and DR retinas. Various CK2 antibodies primarily reacted with astrocytes in human, mouse and rat retinas. These cells actively participate in angiogenesis during retinal development. In neovascularized mouse and rat retinas, the staining for CK2 increased in the inner retinas where new intraretinal vessels were concentrated close to the inner limiting membrane. Most of these vessels were in an intimate contact with astrocytes identified by CK2 and GFAP staining. In accordance with previous data CK2 inhibitors and octreotide each significantly reduced retinal neovascularization in the mouse retinopathy model. A combination of these compounds produced a stronger effect than each of them alone. Conclusions: All CK2 subunits were expressed in retina. CK2 appears to be a specific marker of retinal astrocytes that stimulate retinal angiogenesis. Naturally derived CK2 inhibitors, such as emodin, could be useful for treatment of proliferative retinopathies, either alone or in combination with angiogenic compounds with a different mechanism of action, such as octreotide.

Keywords: retinal glia • retinal neovascularization • diabetic retinopathy