Raman spectroscopic evaluation of protein modification: a new, non-invasive diagnostic tool for age-related eye disease

Rapid, non-invasive evaluation of robust markers of disease progression in the eyes of aging patients would provide a novel and exciting basis for recognising risk of visual loss and perhaps also link to other age-related diseases such as cataract formation and glaucoma. The proposed project builds on knowledge from the scientific literature, strong international collaboration and key preliminary findings. It will seek to establish a firm basis for using confocal Raman microscopy and spectroscopic evaluation of patients to study chemical modifications called advanced glycation endproducts (AGEs) in the eye. The approach is multidisciplinary and represents collaboration between vision scientists, physical chemists, ophthalmologists and optometrists. Together, this unusual team can offer a unique perspective on a pressing research problem. The project will ascertain age-related risk in a patient-based evaluation of AGE-mediated Raman spectra in ocular tissues. With appropriate identification, quantification and validation of AGE moieties in the eye and their correlation with age-mediated pathophysiology, Raman spectra could ultimately form an important, non-invasive diagnostic tool for AMD and other age-associated ocular defects.

Age-related macular degeneration (AMD) remains the leading cause of irreversible blindness in older people in the UK and clinical intervention options for AMD are severely limited. We still know remarkably little about this important retinal disease and although age remains the main risk factor, the associated progression from sub-clinical age-related maculopathy (ARM) is ambiguous. There is no firm basis for early diagnosis of the ~2.2 million people in the UK who are affected by AMD.
Rapid, non-invasive evaluation of robust markers of disease progression in the eyes of ageing patients would provide a novel and exciting basis for recognizing age-related risk from potentially blinding conditions. The proposed project is truly ?translational? and builds on knowledge from the scientific literature, strong international collaboration and key preliminary findings. It will seek to establish a firm basis for using confocal Raman microscopy of post-mortem clinical material and parallel spectroscopic evaluation of patients to study chemical modifications called advanced glycation endproducts (AGEs) in the eye. The approach is multidisciplinary and, since it brings together an uncommon collaboration between ophthalmic biologists physical chemists and optometrists, offers a unique perspective on a pressing research problem. The project will ascertain age-related risk associated with these harmful adducts in appropriate in vitro experiments, ex vivo studies and complementary evaluation of relevant clinical specimens. In parallel with this research, we propose to conduct a patient-based evaluation of AGE-mediated Raman spectra in ocular tissues. With appropriate identification, quantification and validation of AGE moieties in the eye and their correlation with pathophysiology, Raman spectra could ultimately form an important diagnostic tool for age-related ocular defects in general and progression to AMD in particular.