Symposien Sonntag

Änderungen im Programmablauf vorbehalten.

 
engl
Raum Paris 11:30 - 12:45 02.10.2016
Symposium So16
Complement system and retinal dysfunction
Vorsitzende/r: Diana Pauly (Regensburg), Antje Grosche (Regensburg)

Retinal degenerations are associated with parainflammation and dysregulation of the complement system, a central pathway of the innate immune system. Despite known genetic polymorphisms and described local complement deposition the involved pathomechanism has not been deciphered so far. This symposium presents latest research results concerning complement expression, deposition and function in cell culture and animal models for retinal degenerations.
Referent/in: Imre Lengyel (London)
Accumulation of lipid- and protein-rich drusen and basal linear deposits between the inner collagenous layer of the Bruch’s membrane and the basal lamina of the RPE is a hallmark of early age-related macular degeneration (AMD). Hollow spherules composed of lipids and inorganic hydroxyapatite (HAP) have recently been described within these deposits (PMID 25605911). Recently we were able to recreate protein, lipid and HAP deposition in primary RPE cell culture models and analyze the basal and apical secretome of these cells. With this we are exploring how the complement system is modulated in this model to understand the role the complement system plays in focal and diffuse deposits formation in the sub-RPE space and sub-retinal drusenoid deposit formation in the sub-retinal space. Overall, these cell culture models of early stage AMD can provide us with a unique insight into the molecular events leading to AMD. These will also allow us to develop and test new therapeutic interventions against early stages of AMD, especially those in which the complement system is involved.

Referent/in: Olaf Strauß (Berlin)
Accumulation of complement proteins and polymorphisms in complement genes as risk associates led to the hypothesis that age-related macular degeneration (AMD) is caused by a permanent attack of the retinal pigment epithelium (RPE) by complement. We found that complement does not break down the membrane resistance but generates specifically shaped intracellular Ca2+-signals. We described the contribution of C3aR and C5aR and their signaling pathways. We conclude that complement changes the functional phenotype of RPE cells.
Referent/in: Antje Grosche (Regensburg)
RPE stress owing to complement activation is suggested to promote progression of age-related macular degeneration. It is still being debated whether retinal complement activity primarily results from local complement factor (CF) production or whether CF recruitment from the blood circulation is the key mechanism. Addressing this question, we performed cell type-specific expression analysis comparing CF expression in neurons, vascular cells, micro- and Müllerglia with that in RPE/choroid collected from two mouse models of retinal degeneration.
Referent/in: Seba Almedawar (Dresden)
There is growing evidence that complement activation in the RPE is involved in the pathogenesis of retinal degenerative diseases such as AMD. In our lab we have established a protocol to differentiate stem cells to RPE cells that resemble on the functional and morphological level primary human RPE and are therefore suitable to study complement system expression patterns in healthy and stressed RPE cells. To this end, we stressed the cells using H2O2 and human serum and isolated RNA from healthy and stressed cells for expression profile analysis of 8 complement factors using qPCR.
Referent/in: Diana Pauly (Regensburg)
The complement system is involved in progression of retinal degeneration. However, there is uncertainty whether systemic or local complement promotes local immune reactions. Analysis of mRNA and protein expression patterns of eight complement factors in the retina and RPE/choroid of light-treated mice showed both a local and systemic regulation of different complement factors. We determined three marker proteins, which will be used in further studies to decipher the complement-associated pathomechanism in retinal degeneration.