Bests Disease is a dominantly inherited, early onset macular degenerative disease and exhibits some histopathologic similarities to age-related macular degeneration (AMD). The diagnostic hallmark of Bests disease is a markedly reduced light peak (LP) in the electrooculogram (EOG), with no aberrations in the """"""""a"""""""" or """"""""b"""""""" waves of the electroretinogram (ERG). It has been shown that the gene mutated in Best disease, VMD2, encodes the bestrophin protein. It was initially hypothesized that Bestrophin might be responsible for LP generation because it acts as Ca2+-activated Cl- channel and is localized to the its basolateral membrane. However, there is now considerable evidences that L-type VDCC is involved in the generation of LP. Systemic application of the L-type Ca2+ channel blocker nimodipine reduced the light-peak amplitude in rat and mouse models. The light peak was also diminished in Cav1.3 knock-out mice or Lethargic mice which harbor a functional loss of the VDCC 4 subunit. All this findings help establish a role for L-type Ca2+ channel in LP generation. In the present study, we first identified the expression profiles of all types of voltage-dependent Ca2+ channels in native and cultured fetal RPE cells using Quantitative Real-Time PCR array, and then characterized the expression and membrane localization with Western blot and immunocytochemistry. Furthermore, intracellular microelectrodes and Ca2+ imaging were used to characterize their possible second messenger pathways and downstream electrophysiological properties at the apical and basolateral membranes.
