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

Lead Research Organisation: Queen's University of Belfast
Department Name: Medicine Dentistry and Biomedical Sci

Abstract

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.

Technical Summary

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.

Publications

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Beattie JR (2013) Raman spectroscopy for the detection of AGEs/ALEs. in Methods in molecular biology (Clifton, N.J.)

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Beattie JR (2010) Multiplex analysis of age-related protein and lipid modifications in human Bruch's membrane. in FASEB journal : official publication of the Federation of American Societies for Experimental Biology

 
Title Raman analysis software 
Description Unique software to analyse complex Raman spectra in biological tissue. 
Type Of Material Data analysis technique 
Provided To Others? No  
Impact Combined with the new spectroscope, this software allows rapid analysis of Raman data 
 
Description Sharing of reagents/resources 
Organisation University of California, San Diego (UCSD)
Department Department of Pathology
Country United States 
Sector Academic/University 
PI Contribution The collaboration was based on chemical synthesis expertise from the Case Western Partner (Prof Vicent Monnier)
Collaborator Contribution Sharing of AGE moieties for our research
Impact FASEB J. 2010 Dec;24(12):4816-24.
Start Year 2009
 
Description Use of human ocular specimens 
Organisation University of Florida
Department College of Medicine
Country United States 
Sector Academic/University 
PI Contribution Prof Mike Boulton provided expertise and access to clinical samples
Impact Glenn JV, Mahaffy H, Wu K, Smith G, Nagai R, Simpson DA, Boulton ME, Stitt AW. Advanced glycation end product (AGE) accumulation on Bruch's membrane: links to age-related RPE dysfunction. Invest Ophthalmol Vis Sci. 2009 Jan;50(1):441-51. Beattie JR, Pawlak AM, Boulton ME, Zhang J, Monnier VM, McGarvey JJ, Stitt AW. Multiplex analysis of age-related protein and lipid modifications in human Bruch's membrane. FASEB J. 2010 Dec;24(12):4816-24. Glenn JV, Mahaffy H, Dasari S, Oliver M, Chen M, Boulton ME, Xu H, Curry WJ, Stitt AW. Proteomic profiling of human retinal pigment epithelium exposed to an advanced glycation-modified substrate. Graefes Arch Clin Exp Ophthalmol. 2011 Nov 13. [Epub ahead of print]
Start Year 2008
 
Description Patient groups 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The talk was presented to patients and fund-raisers for ophthalmic research. They were given the opportunity learn about basic research ongoing in our laboraotry and the potential for transaltion into patient care.

Those attending were excited by the possibilities and interested to know how science is conducted
Year(s) Of Engagement Activity 2010,2011,2012,2013,2014,2016,2017