TY - JOUR A1 - Tarau, Ioana-Sandra A1 - Berlin, Andreas A1 - Curcio, Christine A. A1 - Ach, Thomas T1 - The cytoskeleton of the retinal pigment epithelium: from normal aging to age-related macular degeneration JF - International Journal of Molecular Science N2 - The retinal pigment epithelium (RPE) is a unique epithelium, with major roles which are essential in the visual cycle and homeostasis of the outer retina. The RPE is a monolayer of polygonal and pigmented cells strategically placed between the neuroretina and Bruch membrane, adjacent to the fenestrated capillaries of the choriocapillaris. It shows strong apical (towards photoreceptors) to basal/basolateral (towards Bruch membrane) polarization. Multiple functions are bound to a complex structure of highly organized and polarized intracellular components: the cytoskeleton. A strong connection between the intracellular cytoskeleton and extracellular matrix is indispensable to maintaining the function of the RPE and thus, the photoreceptors. Impairments of these intracellular structures and the regular architecture they maintain often result in a disrupted cytoskeleton, which can be found in many retinal diseases, including age-related macular degeneration (AMD). This review article will give an overview of current knowledge on the molecules and proteins involved in cytoskeleton formation in cells, including RPE and how the cytoskeleton is affected under stress conditions — especially in AMD. KW - retinal pigment epithelium KW - cytoskeleton KW - aging KW - age-related macular degeneration KW - actin KW - microfilament KW - microtubules KW - stress fiber Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201781 SN - 1422-0067 VL - 20 IS - 14 ER - TY - JOUR A1 - Richert, Elisabeth A1 - Koinzer, Stefan A1 - Tode, Jan A1 - Schlott, Kerstin A1 - Brinkmann, Ralf A1 - Hillenkamp, Jost A1 - Klettner, Alexa A1 - Roider, Johann T1 - Release of Different Cell Mediators During Retinal Pigment Epithelium Regeneration Following Selective Retina Therapy JF - Investigative Ophthalmology & Visual Science N2 - PURPOSE. To investigate the effect of selective retina therapy (SRT) on the release of AMD-relevant cell mediators, such as matrix metalloproteinases (MMPs), VEGF, and pigment epithelium derived factor (PEDF) using different laser spot sizes and densities. METHODS. Porcine RPE-choroid explants were treated with a pulsed 532 nm Nd:YAG laser using (1) large spot sizes, (2) small spot sizes with a high-density (hd) treatment, and (3) small spot sizes with a low-density (1d) treatment. Explains were cultivated in modified Ussing chambers. RPE regeneration and RPE cell death were investigated by calcein-AM staining and immunofluorescence. The MMP release was examined via zymography and immunofluorescence. VEGF and PEDF secretion was analyzed by ELISA. RESULTS. During pigment epithelium regeneration (PER), mitosis and RPE cell migration were observed. Four days after SRT (large spot size) the content of active MMP2 increased significantly (P < 0.01). Hd treatment with small spot sizes resulted also in an increase of active MMP2 (P < 0.05). In immunofluorescence explants showed a localized expression of MMP2 within the healing lesions after irradiation. The PEDF level increased significantly (P = 0.01) after SRT with large spot sizes. VEGF secretion decreased significantly (P < 0.05) following SRT with large spot sizes and with hd treatment of small spot sizes. CONCLUSIONS. SRT induces a cytokine profile, which may improve the flux across Brach's membrane, slows down progression of early AMD by RPE regeneration, and inhibits the formation of choroidal neovascularization. The cytokine release depends on the size and density of applied laser spots. KW - age-related macular degeneration KW - matrix metalloproteases KW - pigment epithelium derived factor KW - retinal pigment epithelium KW - selective retina therapy KW - vascular endothelial growth factor Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226161 VL - 59 IS - 3 ER - TY - JOUR A1 - Fernandez-Robredo, P. A1 - Sancho, A. A1 - Johnen, S. A1 - Recalde, S. A1 - Gama, N. A1 - Thumann, G. A1 - Groll, J. A1 - Garcia-Layana, A. T1 - Current Treatment Limitations in Age-Related Macular Degeneration and Future Approaches Based on Cell Therapy and Tissue Engineering JF - Journal of Ophtamology N2 - Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. With an ageing population, it is anticipated that the number of AMD cases will increase dramatically, making a solution to this debilitating disease an urgent requirement for the socioeconomic future of the European Union and worldwide. The present paper reviews the limitations of the current therapies as well as the socioeconomic impact of the AMD. There is currently no cure available for AMD, and even palliative treatments are rare. Treatment options show several side effects, are of high cost, and only treat the consequence, not the cause of the pathology. For that reason, many options involving cell therapy mainly based on retinal and iris pigment epithelium cells as well as stem cells are being tested. Moreover, tissue engineering strategies to design and manufacture scaffolds to mimic Bruch's membrane are very diverse and under investigation. Both alternative therapies are aimed to prevent and/or cure AMD and are reviewed herein. KW - endothelial growth factor KW - pluripotent stem cells KW - subfoveal choroidal neovascularization KW - human bruchs membrane KW - ciliary neurotrophic factor KW - randomized clinical trial KW - dystrophic RCS rats KW - subretinal space KW - in-vitro KW - retinal pigment epithelium Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-118004 SN - 2090-0058 IS - 510285 ER -