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.
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
Pawlak AM
(2008)
Advanced glycation as a basis for understanding retinal aging and noninvasive risk prediction.
in Annals of the New York Academy of Sciences
Milne R
(2013)
Advanced glycation end products and diabetic retinopathy.
in Amino acids
Stitt AW
(2010)
AGEs and diabetic retinopathy.
in Investigative ophthalmology & visual science
Glenn JV
(2007)
Confocal Raman microscopy can quantify advanced glycation end product (AGE) modifications in Bruch's membrane leading to accurate, nondestructive prediction of ocular aging.
in FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Duh EJ
(2017)
Diabetic retinopathy: current understanding, mechanisms, and treatment strategies.
in JCI insight
Beattie J
(2009)
Effect of signal intensity normalization on the multivariate analysis of spectral data in complex 'real-world' datasets
in Journal of Raman Spectroscopy
Medina RJ
(2012)
Endothelial progenitors as tools to study vascular disease.
in Stem cells international
Medina RJ
(2017)
Endothelial Progenitors: A Consensus Statement on Nomenclature.
in Stem cells translational medicine
Beattie J
(2013)
Estimation of signal backgrounds on multivariate loadings improves model generation in face of complex variation in backgrounds and constituents Multivariate background correction + model performance
in Journal of Raman Spectroscopy
Medina RJ
(2011)
Eyes open to stem cells: safety trial may pave the way for cell therapy to treat retinal disease in patients.
in Stem cell research & therapy
Beattie JR
(2009)
Identifying the spatial distribution of vitamin E, pulmonary surfactant and membrane lipids in cells and tissue by confocal Raman microscopy.
in Methods in molecular biology (Clifton, N.J.)
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
Medina RJ
(2011)
Myeloid angiogenic cells act as alternative M2 macrophages and modulate angiogenesis through interleukin-8.
in Molecular medicine (Cambridge, Mass.)
Beattie J
(2011)
Optimising reproducibility in low quality signals without smoothing; an alternative paradigm for signal processing Optimising reproducibility in low quality signals without smoothing
in Journal of Raman Spectroscopy
Reid E
(2018)
Preclinical Evaluation and Optimization of a Cell Therapy Using Human Cord Blood-Derived Endothelial Colony-Forming Cells for Ischemic Retinopathies.
in Stem cells translational medicine
Beattie JR
(2012)
Profiling retinal biochemistry in the MPDZ mutant retinal dysplasia and degeneration chick: a model of human RP and LCA.
in Investigative ophthalmology & visual science
Glenn JV
(2012)
Proteomic profiling of human retinal pigment epithelium exposed to an advanced glycation-modified substrate.
in Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
Beattie JR
(2013)
Raman spectroscopy for the detection of AGEs/ALEs.
in Methods in molecular biology (Clifton, N.J.)
Pawlak A
(2008)
Raman spectroscopy of advanced glycation end products (AGEs), possible markers for progressive retinal dysfunction
in Journal of Raman Spectroscopy
Beattie JR
(2011)
Sclera as a surrogate marker for determining AGE-modifications in Bruch's membrane using a Raman spectroscopy-based index of aging.
in Investigative ophthalmology & visual science
Nagaraj RH
(2012)
The pathogenic role of Maillard reaction in the aging eye.
in Amino acids
Glenn JV
(2009)
The role of advanced glycation end products in retinal ageing and disease.
in Biochimica et biophysica acta
Chambers SEJ
(2018)
The Vasoreparative Function of Myeloid Angiogenic Cells Is Impaired in Diabetes Through the Induction of IL1ß.
in Stem cells (Dayton, Ohio)
Stitt AW
(2011)
Vascular stem cells and ischaemic retinopathies.
in Progress in retinal and eye research
| 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 |