Projects 2007

Sponsoring Laboratory/Section:

Laboratory of Integrative and Medical Biophysics Section on Medical Biophysics
National Institute of Child Health and Human Development (NICHD)

Section Chief/Mentor:

Robert F Bonner, Ph.D.

Contact Information:

e-mail: bonner@helix.nih.gov
phone: (301)435-1946
fax: (301)435-5035

Laboratory Description and Project area:

We are examining photophysics of undegradable fluorescent molecules (A2E and its oxidation products) created in the human retinal photoreceptors principally during periods of bright daylight and then accumulated in lipofuscin granules within the retinal pigment epithelium (RPE) during natural aging. We hypothesize that spectral imbalance between the photochemistries that create the precursors of A2E and those that oxidize A2E within the RPE plays a significant role in early stages of Age-Related Macular Degeneration (AMD, the most common cause of blindness in the US) and that this imbalance with aging can be easily restored. Working in cell culture and in vivo in a mouse double knockout model of AMD, we are seeking to characterize the natural photochemical conversion among various photochemically active species and to develop a model of the changes in the distributions of these species that may accompany changes in the spectral transmission of the human lens with aging. We use scanning confocal microscopy for our in vitro experiments and are adapting clinical Scanning Laser Ophthalmoscopes in order to examine whether dynamics of shifts in the populations of different related photosensitizers can be induced and observed noninvasively in our animal model. We are pursuing pilot clinical imaging studies based on these results to characterize early stages of AMD by autofluorescence imaging and whether specially designed sunglasses (spectral filters) can alter and restore the presumed natural balance.

We are also working on improving image analysis methods for detecting and quantifying change in early lesions in AMD autofluorescence images.