Synapse and Receptor Alterations in Two Different S100B-Induced Glaucoma-Like Models

Glaucoma is identified by an irreversible retinal ganglion cell (RGC) loss and optic nerve damage. Over the past few years, the immune system gained importance in its genesis. In a glaucoma-like animal model with intraocular S100B injection, RGC death occurs at 14 days. In an experimental autoimmune glaucoma model with systemic S100B immunization, a loss of RGCs is accompanied by a decreased synaptic signal at 28 days. Here, we aimed to study synaptic alterations in these two models. In one group, rats received a systemic S100B immunization (n = 7/group), while in the other group, S100B was injected intraocularly (n = 6–7/group). Both groups were compared to appropriate controls and investigated after 14 days. While inhibitory post-synapses remained unchanged in both models, excitatory post-synapses degenerated in animals with intraocular S100B injection (p = 0.03). Excitatory pre-synapses tendentially increased in animals with systemic S100B immunization (p = 0.08) and significantly decreased in intraocular ones (p = 0.04). Significantly more N-methyl-d-aspartate (NMDA) receptors (both p ≤ 0.04) as well as gamma-aminobutyric acid (GABA) receptors (both p < 0.03) were observed in S100B animals in both models. We assume that an upregulation of these receptors causes the interacting synapse types to degenerate. Heightened levels of excitatory pre-synapses could be explained by remodeling followed by degeneration

Veränderungen von retinalen Synapsen und Rezeptoren in zwei verschiedenen S100B-induzierten Glaukom-ähnlichen Modellen

Zur Erforschung des Glaukom-Pathomechanismus wurden zwei verschiedene Glaukom-ähnliche Modelle in der Ratte verwendet. Im Experimentellen Autoimmunen Glaukom-Modell (EAG) wurde S100B systemisch injiziert, im Intraokulären Glaukom-ähnlichen Modell intravitreal. Retinale Ganglienzellen (RGZ), inhibitorische Postsynapsen, exzitatorische Prä- und Postsynapsen sowie NMDA und GABA Rezeptoren wurden 14 Tage nach der Injektion immunhistochemisch untersucht. RGZs im EAG-Modell als auch inhibitorischen Postsynapsen in beiden Modellen zeigten sich unverändert. Exzitatorischen Postsynapsen degenerierten nach intraokulärer S100B Injektion. Exzitatorische Präsynapsen waren tendenziell nach systemischer S100B Injektion erhöht, nach intraokulärer signifikant erniedrigt. In beiden Modellen konnte sowohl eine Hochregulation der NMDA als auch der GABA Rezeptoren detektiert werden

Proteomic Analysis of Retinal Tissue in an S100B Autoimmune Glaucoma Model

Glaucoma is a neurodegenerative disease that leads to damage of retinal ganglion cells and the optic nerve. Patients display altered antibody profiles and increased antibody titer, e.g., against S100B. To identify the meaning of these antibodies, animals were immunized with S100B. Retinal ganglion cell loss, optic nerve degeneration, and increased glial cell activity were noted. Here, we aimed to gain more insights into the pathophysiology from a proteomic point of view. Hence, rats were immunized with S100B, while controls received sodium chloride. After 7 and 14 days, retinae were analyzed through mass spectrometry and immunohistology. Using data-independent acquisition-based mass spectrometry, we identified more than 1700 proteins on a high confidence level for both study groups, respectively. Of these 1700, 43 proteins were significantly altered in retinae after 7 days and 67 proteins revealed significant alterations at 14 days. For example, α2-macroglobulin was found significantly increased not only by mass spectrometry analysis, but also with immunohistological staining in S100B retinae at 7 and 14 days. All in all, the identified proteins are often associated with the immune system, such as heat shock protein 60. Once more, these data underline the important role of immunological factors in glaucoma pathogenesis

Impact of trophic state on the distribution of intact polar lipids in surface waters of lakes

We characterized the intact polar lipid (IPL) composition in the surface waters of 22 lakes from Minnesota and Iowa, ranging in trophic state between eutrophic and oligo-mesotrophic, to investigate the impact of trophic state on IPL composition. A high diversity of IPL classes was detected. Most IPL classes were detected in all lakes, but the eutrophic lakes contained a significantly higher relative abundance of lyso-phosphatidylcholine (PC) than the oligo-mesotrophic lakes, which in turn were characterized by significantly higher relative abundance of hydroxymethyltrimethyl-alanine/trimethyl-homoserine (DGTA/DGTS) betaines, ornithine lipids and the recently discovered trimethyl ornithine (TMO) lipids. The higher relative abundance of ornithines and TMOs may relate to a higher contribution of heterotrophic bacteria relative to phytoplankton while the higher abundance of the DGTA/DGTS betaines may relate to substitution by microorganisms of these non-P lipids for PC under P-stress, as has been observed in other environments. We also detected a variety of heterocyst glycolipids (HGs) derived from N2-fixing heterocystous Cyanobacteria in all lakes, suggesting the presence of these Cyanobacteria in the full range of trophic conditions. Correlation of HG abundance with environmental data showed that high productivity lakes have high HG abundances, while other distributional differences in HGs, which did not correlate with environmental parameters, are likely due to differences in species composition. We conclude that the significant differences in IPL composition between the eutrophic and oligo-mesotrophic lakes are either due to adaptation of the membrane composition to nutrient conditions or due to general divergences in microbial composition under the different conditions