11-cis-retinal and Eye-Diseases

In the first part of the paper, the results of the investigation of the rhodopsin arrestin interaction are presented. The results were mainly obtained with the technique of the selective labelling of the rhodopsin and arrestin SH-groups and the rhodopsin limited proteolysis. These results are discussed in the frame of the latest data on the three-dimensional structure of arrestin. In the second part of the paper, results of the antigenic properties of arrestin (S-antigen) and its role in the pathogenesis of the retina diseases are summarized. The data on the role of the autoimmune processes in the pathogenesis of diabetic retinopathy are presented. We have also described the results of the use of the elaborated technique of the immune diagnostics in the prognosis of the diabetic retinopathy and retinopathy of the premature babies.

Topics: Animals; Arrestin; Autoimmune Diseases; Eye Diseases; Humans; Infant, Newborn; Infant, Premature; Protein Binding; Retinal Diseases; Rhodopsin; Vision, Ocular

Recent advances in stem cell research have raised the possibility of stem cells repairing or replacing retinal photoreceptor cells that are either dysfunctional or lost in many retinal diseases. Various types of stem cells have been used to replace retinal photoreceptor cells. Recently, peripheral blood stem cells, a small proportion of pluripotent stem cells, have been reported to mainly exist in the peripheral blood mononuclear cells (PBMCs).. In this study, the effects of pre-induced adult human PBMCs (hPBMCs) on the degenerative retinas of rd1 mice were investigated. Freshly isolated adult hPBMCs were pre-induced with the use of the conditioned medium of rat retinas for 4 days and were then labeled with chloromethyl-benzamidodialkylcarbocyanine (CM-DiI) and then transplanted into the subretinal space of the right eye of rd1 mice through a trans-scleral approach. The right eyes were collected 30 days after transplantation. The survival and migration of the transplanted cells in host retinas were investigated by whole-mount retinas, retinal frozen sections and immunofluorescent staining.. After subretinal transplantation, pre-induced hPBMCs were able to survive and widely migrate into the retinas of rd1 mice. A few CM-DiI-labeled cells migrated into the inner nuclear layer and the retinal ganglion cell layer. Some transplanted cells in the subretinal space of rd1 host mice expressed the human photoreceptor-specific marker rhodopsin.. This study suggests that pre-induced hPBMCs may be a potential cell source of cell replacement therapy for retinal degenerative diseases.

Topics: Animals; Cell Movement; Cell Survival; Culture Media, Conditioned; Electroretinography; Eye Diseases; Humans; Leukocytes, Mononuclear; Mice; Photoreceptor Cells, Vertebrate; Pluripotent Stem Cells; Rats; Retina; Rhodopsin

Topics: Animals; Calcium Channels; Cell Proliferation; Cell Survival; Eye Diseases; Fingolimod Hydrochloride; Humans; Immunosuppressive Agents; Intermediate Filament Proteins; Lysophospholipids; Membrane Glycoproteins; Nerve Tissue Proteins; Opsins; Peripherins; Propylene Glycols; Receptors, Lysosphingolipid; Retinal Photoreceptor Cell Outer Segment; Rhodopsin; Sphingosine

The thermal properties of rhodopsin, which set the threshold of our vision, have long been investigated, but the chemical kinetics of the thermal decay of rhodopsin has not been revealed in detail. To understand thermal decay quantitatively, we propose a kinetic model consisting of two pathways: 1) thermal isomerization of 11-cis-retinal followed by hydrolysis of Schiff base (SB) and 2) hydrolysis of SB in dark state rhodopsin followed by opsin-catalyzed isomerization of free 11-cis-retinal. We solve the kinetic model mathematically and use it to analyze kinetic data from four experiments that we designed to assay thermal decay, isomerization, hydrolysis of SB using dark state rhodopsin, and hydrolysis of SB using photoactivated rhodopsin. We apply the model to WT rhodopsin and E181Q and S186A mutants at 55 °C, as well as WT rhodopsin in H(2)O and D(2)O at 59 °C. The results show that the hydrogen-bonding network strongly restrains thermal isomerization but is less important in opsin and activated rhodopsin. Furthermore, the ability to obtain individual rate constants allows comparison of thermal processes under various conditions. Our kinetic model and experiments reveal two unusual energetic properties: the steep temperature dependence of the rates of thermal isomerization and SB hydrolysis in the dark state and a strong deuterium isotope effect on dark state SB hydrolysis. These findings can be applied to study pathogenic rhodopsin mutants and other visual pigments.

Topics: Animals; Cattle; Evolution, Molecular; Eye Diseases; HEK293 Cells; Humans; Hydrogen Bonding; Hydrolysis; Kinetics; Models, Theoretical; Mutation; Retinitis Pigmentosa; Rhodopsin; Schiff Bases; Temperature