Multimodal imaging, packing geometry and autofluorescence properties of human retinal pigment epithelium cells as a function of age and age-related macular degeneration

• Applicant: Privatdozent Dr. Thomas Ach
• Subject Area: Ophthalmology
• Term: from 2012 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 225227250

Retinal pathologies like age-related macular degeneration (AMD) are the most common reasons for irreversible visual loss in the western hemisphere.Underlying changes at the level of the retinal pigment epithelium (RPE) are not completely understood yet. The accumulation of the autofluorescent (AF) fluorophore mixture lipofuscin (LF) in RPE cells are widely believed to cause cell death and advanced AMD, yet cellular level data from human eyes supporting that concept are limited. In vivo AF-images of the human fundus reveal only raw patterns of AF distribution and allow few conclusions to be drawn with respect to LF distribution in RPE cells and the functional status of these cells.In this project, a digital map of human RPE topography and packing geometry will be generated using flat mounted chorioretinal tissues from eyes of different ages and stages of AMD. At well-defined areas in the macula and periphery (about 75 points), multiple images will be taken using stereo color, infrared, red-free and autofluorescent imaging methods to determine RPE cell number and distribution. Furthermore, the spectral properties AF intensities of RPE cells at these points will be investigated. The histological studies will be complemented by AF measurements at a sub-cellular level. Using structured illumination, a new laser optic high resolution microscopically technique, the AF spectral properties of single intracellular LF granules and the fluorophore distribution within these granules will be examined. The raw in vivo patterns will be correlated with AF patterns at cellular and sub-cellular levels. This will be maintained in a sub-nanometer range by the use of structured illumination.Other ongoing laboratory projects using ex vivo optical coherence tomography imaging and macula-wide high-resolution histological sections will serve as a unique resource for enhancing the results of this study. Our expected results can provide an improved basis for interpreting clinical in vivo AF fundus images. This technique is now widely available on commercial instruments. In conclusion, this project will enhance the knowledge of RPE packing geometry, LF pathogenesis, AF distribution, and AMD progression intended to inform the interpretation of current and next-generation clinical imaging of retina.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Christine Curcio, Ph.D.