ProjectNovel Biomarkers for Mobus Stargardt: Flavoprotein Fluorescence and Beyond
Basic data
Title:
Novel Biomarkers for Mobus Stargardt: Flavoprotein Fluorescence and Beyond
Duration:
01/08/2024 to 30/09/2026
Abstract / short description:
Stargardt's disease, an inherited eye disorder primarily caused by ABCA4 gene mutations, leads to progressive
loss of central vision due to the degeneration of macular photoreceptor cells. There is no approved treatment,
but several therapeutic approaches are tested in clinical trials. Here, traditional measures like visual acuity are
inadequate for evaluating treatment efficacy due to the disease's slow progression. The ProgStar trials have set
standardized clinical trial endpoints and proved that fundus autofluorescence (FAF) imaging and optical
coherence tomography (OCT) are able to provide well-suited markers for disease progression. However, these
techniques obligatorily rely on visible structural changes and are therefore unable to detect earlier
pathophysiological alterations. Here, flavoprotein fluorescence (FPF) imaging provides a promising non-invasive
method for assessing retinal cell viability, even in the absence of structural damage. Flavoproteins are proteins
that fulfill essential tasks in several metabolic pathways, most importantly in oxidative phosphorylation.
Intriguingly, flavoproteins exhibit a green fluorescence in their oxidized but no in the reduced state. Therefore,
metabolic stress, which leads to accumulation of oxidized flavoproteins, can be non-invasively visualized in
living tissues using FPF imaging. Only recently, the OcuMet Beacon (Ocusciences Inc, Ann Arbor, MI, USA), the
first commercially available FPF device, was introduced, which allow to take FPF images of a patient’s retina.
Based on the ability to visualize metabolic stress in a non-invasive way, FPF has the potential to provide a
novel, highly sensitive endpoint for clinical trials. However, only a limited number of reports on FPF in retinal
diseases have been published and detailed data on the correlation between structural readouts, like FAF and
OCT, or location-specific functional measures, like for example fundus controlled perimetry, are completely
lacking. Therefore, this study aims to significantly extend our understanding of FPF imaging in human subjects
and test the feasibility of FPF imaging to provide novel biomarkers for disease progression in Stargardt’ disease.
loss of central vision due to the degeneration of macular photoreceptor cells. There is no approved treatment,
but several therapeutic approaches are tested in clinical trials. Here, traditional measures like visual acuity are
inadequate for evaluating treatment efficacy due to the disease's slow progression. The ProgStar trials have set
standardized clinical trial endpoints and proved that fundus autofluorescence (FAF) imaging and optical
coherence tomography (OCT) are able to provide well-suited markers for disease progression. However, these
techniques obligatorily rely on visible structural changes and are therefore unable to detect earlier
pathophysiological alterations. Here, flavoprotein fluorescence (FPF) imaging provides a promising non-invasive
method for assessing retinal cell viability, even in the absence of structural damage. Flavoproteins are proteins
that fulfill essential tasks in several metabolic pathways, most importantly in oxidative phosphorylation.
Intriguingly, flavoproteins exhibit a green fluorescence in their oxidized but no in the reduced state. Therefore,
metabolic stress, which leads to accumulation of oxidized flavoproteins, can be non-invasively visualized in
living tissues using FPF imaging. Only recently, the OcuMet Beacon (Ocusciences Inc, Ann Arbor, MI, USA), the
first commercially available FPF device, was introduced, which allow to take FPF images of a patient’s retina.
Based on the ability to visualize metabolic stress in a non-invasive way, FPF has the potential to provide a
novel, highly sensitive endpoint for clinical trials. However, only a limited number of reports on FPF in retinal
diseases have been published and detailed data on the correlation between structural readouts, like FAF and
OCT, or location-specific functional measures, like for example fundus controlled perimetry, are completely
lacking. Therefore, this study aims to significantly extend our understanding of FPF imaging in human subjects
and test the feasibility of FPF imaging to provide novel biomarkers for disease progression in Stargardt’ disease.
Involved staff
Managers
Center for Ophthalmology
Hospitals and clinical institutes, Faculty of Medicine
Hospitals and clinical institutes, Faculty of Medicine
Faculty of Medicine
University of Tübingen
University of Tübingen
Center for Ophthalmology
Hospitals and clinical institutes, Faculty of Medicine
Hospitals and clinical institutes, Faculty of Medicine
Local organizational units
University Eye Hospital
Center for Ophthalmology
Hospitals and clinical institutes, Faculty of Medicine
Hospitals and clinical institutes, Faculty of Medicine
Funders
Frankfurt am Main, Hessen, Germany