gms | German Medical Science

Secretion of various growth factors by the retinal pigment epithelium (RPE) is substantial for normal structure of the retina but also plays a role in the etiology of retinal diseases. Further, the RPE itself is the target of cytokines. L-type Ca²⁺ channels are mediating intracellular processing from incoming signals and subsequent growth factor secretion. Purpose of this study was to resolve the molecular structure of the Ca²⁺ channels expressed by the RPE and to compare it to those of patients with choroidal neovascularization (CNV).

The biophysical properties of Ca²⁺ currents in the RPE were investigated by the patch-clamp technique. The complete coding sequence of the pore forming α subunit of the human RPE cell line ARPE-19 and from patients with CNV was cloned and the expression pattern of accessory subunits was investigated by RT-PCR.

The RPE from patients with CNV show Ba²⁺ currents similar to the Ba²⁺ currents in ARPE-19 cells. Both were reduced by the specific inhibitor nifedipine and stimulated by BayK 8644. The currents displayed unusual fast inactivation kinetics. We found differences between ARPE-19 cells and CNV in the pore forming α subunit Ca_v1.3 as well as in the expression pattern of the accessory Ca²⁺ channel subunits.

The Ba²⁺ currents we found in RPE cells displayed dihydropyridine sensitivities like neuroendocrine Ca²⁺ channels. Consistently, we revealed the splice-variant of the Ca_v1.3 α subunit expressed in the RPE. The obvious differences in the inactivation kinetics between neuroendocrine Ca²⁺ channels in the RPE and other cells may be explained by a yet unknown regulation mechanism of the channels in the RPE. These differences may be caused by the expression of the splicing variant and the expression pattern of accessory subunits.