Highlights in Translational Science
Forschung ist das Fundament einer zukunftsfähigen Augenheilkunde. In den vier Sitzungen dieses neuen Formats werden klinische Probleme wie etwa die altersbedingte Makuladegeneration oder das trockene Auge aus verschiedenen Blickwinkeln von Klinikern und Forschern betrachtet, sodass diese sich sinnvoll ergänzen können. In jeder Sitzung wird das jeweils beste Abstract gekürt, gestiftet von der Roche Pharma AG.
|Saal 3||15:00 - 16:15||28.09.2019|
|Highlights in Translational Science: AMD|
Despite major advances in understanding pathogenetic factors in multifactorial, complex AMD, there are many open questions to be addressed. Likewise, with 10 years of experience with anti-VEGF-therapy, there are still relevant unmet needs including efficacy, duration of action, and optimal therapeutic regimen. Specific phenotypic alterations including geographic atrophy, fibrosis as well as sub-RPE and reticular drusen need to be tackled. Hetereogeneity in natural history and treatment response requires the identification of novel biomakers to allow for personalized healthcare and optimized outcomes in the future.
Active complement proteins accumulate in the outer retina of AMD patients; the terminal complex already at younger ages. Polymorphisms in complement genes represent the genetic background with the highest effect size compared to risk other genes. Polymorphic complement proteins revealed a reduced efficiency to control the alternative activation pathway of the complement system. Increased complement activity leads to local cellular inflammation by induction of the inflammasome or changes of the immunogenic phenotype in RPE cells.
RPE health and disease can be visualized in vivo using different imaging modalities, e.g., spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (AF). In AMD, pathologies are often related to a substantial remodeling of the RPE cell layer and the redistribution of RPE´s intracellular autofluorescent granules, as discovered in recent histological studies examining human AMD retinas. These findings on a cellular and sub-cellular level can perfectly be translated into clinical SD-OCT and fundus AF RPE image interpretation and enhance our knowledge in AMD pathogenesis and disease development and progression.
NLRP3 inflammasome activation in the retinal pigment epithelium is observed in atrophic age-related macular degeneration, and pharmacological NLRP3 inhibition may provide a therapeutic strategy to halt disease progression. We tested novel NLRP3 inhibitory drug candidates (IFM-514, IFM-632; IFM Therapeutics) for their efficacy in human retinal pigment epithelium cells.
Recent advances in molecular genetics and cell biology are elucidating the pathophysiological mechanisms underlying age-related macular degeneration and are helping to identify new therapeutic approaches, such as gene therapy, stem cell therapy, and optogenetics. Several of these approaches have entered the clinical phase of development. In individual patients, disease stage will determine whether the therapeutic strategy should comprise photoreceptor cell rescue to delay or arrest vision loss or retinal replacement for vision restoration.