Project Details
Projekt
Optimizing outcome parameters of photoreceptor- and post-receptoral-specific function for clinical trials in patients with inherited retinal diseases
Applicant
Privatdozent Dr. Cord Huchzermeyer
Subject Area
Ophthalmology
Term
since 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 399400373
The need for improved functional endpoints for treatment effects of novel gene- and cell-based therapies for inherited retinal diseases is widely recognized. Psychophysical measurements are very important because they reflect visual perception of the patients. However, it should be considered that detection of progression may be limited because of redundancy in signal processing. Furthermore, the underlying assumption of intact post-receptoral pathways may not hold. Because inherited retinal diseases mostly affect specific cells or cell functions in the retina, stimuli that isolate particular photoreceptors or retinal signaling pathways are often required. In the first round of the SPP, we examined outcome parameters, which specifically stimulated single photoreceptor types using the silent substitution paradigm with temporally modulated light stimuli. This has many advantages over isolation with chromatic adaptation, for example more reliable isolation and a relatively free choice of adaptation conditions. We were able to demonstrate the feasibility of using these measurements in IRD patients despite severe visual disability and to perform longitudinal measurements.In the next funding period, we want to I) improve longitudinal monitoring with silent-substitution-based techniques, II) investigate post-receptoral mechanisms in IRDs and how these can be exploited for improving functional endpoints, and III) compare losses in photoreceptor-specific temporal contrast sensitivities between photoreceptor types in RPE65-mutation-associated IRDs.To reach these goals, we will: i) improve the measurements with the present LED stimulator, ii) use a novel projector-based 5-primary-stimulator that can create stimuli with excellent spectral, temporal and spatial resolutions and that can stimulate specific retinal areas, and (iii) include electroretinographical measurements reflecting activity of the different photoreceptor types and post-receptoral mechanisms.
DFG Programme
Priority Programmes
Co-Investigator
Professor Dr. Jan Kremers
