Multiomic Mass Spectrometry Imaging to Advance Future Pathological Understanding of Ocular Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Tissue Samples
2.2. Chemicals
2.3. MALDI-MSI Sample Preparation
2.3.1. Sample Washing
2.3.2. On-Tissue Digestion
2.3.3. Matrix Application
2.4. MALDI-MSI Analysis
2.5. LA-ICP-MSI Sample Preparation
LA-ICP-MSI Calibration Arrays
2.6. LA-ICP-MS Analysis
3. Results
3.1. Matrix Application
3.2. MALDI-MSI Results
3.3. LA-ICP-MSI Results
3.3.1. Qualitative LA-ICP-MSI Results
3.3.2. Quantitative LA-ICP-MSI Results
4. Discussion
4.1. MALDI Sample Preparation Optimization
4.2. MALDI-MSI
4.3. LA-ICP-MSI
4.3.1. Qualitative Imaging
4.3.2. Quantitative Imaging
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviation
Abbreviation | Definition |
AMD | Age-Related Macular Degeneration |
AREDS | Age Related Eye Disease Study |
CCS | Copper Chaperone for Superoxide Dismutase |
CHCA | A-Cyano-4-Hydroxycinnamic Acid |
CMC | Carboxymethylcellulose |
FWHM | Full Width at Half Maximum |
ICP | Inductively Coupled Plasma |
LA | Laser Ablation |
MALDI | Matrix Assistance Laser Desorption Ionisation |
MRT | Multi-Reflecting Time-Of-Flight |
MS | Mass Spectrometry |
MSI | Mass Spectrometry Imaging |
NAD | Nicotinamide Adenine Dinucleotide |
ND | Neutral Density |
Nd:YAG | Neodymium-Doped Yttrium Aluminium Garnet |
NIH | National Institutes of Health |
ppm | Parts Per Million |
PRRs | Patter Recognition Receptors |
PSMG4 | Proteasome Assembly Chaperone 4 |
SARM1 | Sterile Alpha and TIR Motif Containing 1 |
References
- Ash, J.D.; Grimm, C.; Hollyfield, J.G.; Anderson, R.E.; LaVail, M.M.; Bowes Rickman, C. Retinal Degenerative Diseases; Springer: New York, NY, USA; Cham, Switzerland, 2014. [Google Scholar]
- Quartilho, A.; Simkiss, P.; Zekite, A.; Xing, W.; Wormald, R.; Bunce, C. Leading causes of certifiable visual loss in England and Wales during the year ending 31 March 2013. Eye 2016, 30, 602–607. [Google Scholar] [PubMed]
- Wong, L.W.; Su, X.; Li, X.; Cheung, G.M.C.; Klein, R.; Cheng, C.; Wong, T.Y. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: A systematic review and meta-analysis. Lancet Glob. Health 2014, 2, e106–e116. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Papadopoulos, Z. Recent Developments in the Treatment of Wet Age-related Macular Degeneration. Curr. Med. Sci. 2020, 40, 851–857. [Google Scholar] [CrossRef] [PubMed]
- Celkova, L.; Doyle, L.S.; Campbell, M. NLRP3 Inflammasome and Pathobiology in AMD. J. Clin. Med. 2015, 4, 172–192. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martin, F.D.; Maguire, G.M.; Ying, G.; Grunwald, E.J.; Fine, L.S.; Jaffe, G.J. Ranibizumab and Bevacizumab for Neovascular Age-Related Macular Degeneration. N. Engl. J. Med. 2011, 364, 1897–1908. [Google Scholar] [PubMed] [Green Version]
- Doyle, S.; Mulfaul, K.; Fernando, N.; Chirco, K.; Connolly, E.; Ryan, T.; Ozaki, E.; Brennan, K.; Maminishkis, A.; Salomon, R. TLR2 bridges oxidative damage and complement-associated pathology and is a therapeutic target for age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 2018, 59, 3475. [Google Scholar]
- Sarah, D.L.; Campbell, M.; Ozaki, E.; Robert, S.G.; Mori, A.; Paul, K.F.; Gwyneth, F.J.; Kiang, A.-S.; Marian, H.M.; Ed, C.L.; et al. NLRP3 has a protective role in age-related macular degeneration through the induction of IL-18 by drusen components. Nat. Med. 2012, 18, 791–798. [Google Scholar]
- Kosmidou, C.; Efstathiou, E.N.; Hoang, V.M.; Notomi, S.; Konstantinou, K.E.; Hirano, M.; Takahashi, K.; Maidana, E.D.; Tsoka, P.; Young, L.; et al. Issues with the Specificity of Immunological Reagents for NLRP3: Implications for Age-related Macular Degeneration. Sci. Rep. 2018, 8, 461. [Google Scholar] [CrossRef] [Green Version]
- The Age-Related Eye Disease Study Research Group. The effect of five-year zinc supplementation on serum zinc, serum cholesterol and hematocrit in persons randomly assigned to treatment group in the age-related eye disease study: AREDS Report No. 7. J. Nutr. 2002, 132, 697–702. [Google Scholar] [CrossRef] [Green Version]
- Wong, P.C.; Rinaldi, A.N.; Ho, E. Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation. Mol. Nutr. Food Res. 2015, 59, 991–999. [Google Scholar] [CrossRef] [Green Version]
- Winiarczyk, M.; Winiarczyk, D.; Michalak, K.; Kaarniranta, K.; Adaszek, Ł.; Winiarczyk, S.; Mackiewicz, J. Dysregulated Tear Film Proteins in Macular Edema Due to the Neovascular Age-Related Macular Degeneration Are Involved in the Regulation of Protein Clearance, Inflammation, and Neovascularization. J. Clin. Med. 2021, 10, 3060. [Google Scholar] [CrossRef]
- Nordgaard, L.C.; Berg, M.K.; Kapphahn, J.R.; Reilly, C.; Feng, X.; Olsen, W.T.; Ferrington, D.A. Proteomics of the Retinal Pigment Epithelium Reveals Altered Protein Expression at Progressive Stages of Age-Related Macular Degeneration. Investig. Ophthalmol. Vis. Sci. 2006, 47, 815–822. [Google Scholar] [CrossRef]
- Yao, J.; Liu, X.; Yang, Q.; Zhuang, M.; Wang, F.; Chen, X.; Hang, H.; Zhang, W.; Liu, Q. Proteomic analysis of the aqueous humor in patients with wet age-related macular degeneration. Proteomics. Clin. Appl. 2013, 7, 550–560. [Google Scholar] [CrossRef]
- Anderson, G.M.D.; Ablonczy, Z.; Koutalos, Y.; Spraggins, J.; Crouch, K.R.; Caprioli, M.R.; Schey, K.L. High Resolution MALDI Imaging Mass Spectrometry of Retinal Tissue Lipids. J. Am. Soc. Mass Spectrom. 2014, 25, 1394–1403. [Google Scholar] [CrossRef] [Green Version]
- Wills, K.N.; Sadagopa Ramanujam, M.V.; Kalariya, N.; Lewis, R.J.; van Kuijk, F.J.G.M. Copper and zinc distribution in the human retina: Relationship to cadmium accumulation, age, and gender. Exp. Eye Res. 2008, 87, 80–88. [Google Scholar] [CrossRef]
- Erie, C.J.; Good, A.J.; Butz, J.A.; Pulido, J.S. Reduced Zinc and Copper in the Retinal Pigment Epithelium and Choroid in Age-related Macular Degeneration. Am. J. Ophthalmol. 2009, 147, 276–282.e1. [Google Scholar] [CrossRef]
- Erie, C.J.; Butz, A.J.; Good, A.J.; Erie, A.E.; Burritt, F.M.; Cameron, J.D. Heavy Metal Concentrations in Human Eyes. Am. J. Ophthalmol. 2005, 139, 888–893. [Google Scholar] [CrossRef]
- Sang, P.J.; Ju, L.H.; Se, W.J.; Se, K.W.; Kyu, H.P. Five heavy metallic elements and age-related macular degeneration: Korean National Health and Nutrition Examination Survey, 2008–2011. Ophthalmology 2015, 122, 129–137. [Google Scholar]
- Mayer, M.; Frederik, J.G.M. Whole blood selenium in exudativeage-related maculopathy. Acta. Ophthalmol. Scand. 1998, 76, 62–67. [Google Scholar] [CrossRef]
- Heesterbeek, J.T.; Rouhi-Parkouhi, M.; Church, J.S.; Lechanteur, T.Y.; Lorés-Motta, L.; Kouvatsos, N.; Clark, J.S.; Bishop, N.P.; Hoyng, B.C.; den Hollander, I.A.; et al. Association of plasma trace element levels with neovascular age-related macular degeneration. Exp. Eye Res. 2020, 201, 108324. [Google Scholar] [CrossRef]
- Aranaz, M.; Costas Rodriguez, M.; Lobo, L.; González-Iglesias, H.; Vanhaecke, F.; Pereiro, R. Pilot study of homeostatic alterations of mineral elements in serum of patients with age-related macular degeneration via elemental and isotopic analysis using ICP-mass spectrometry. J. Pharm. Biomed. Anal. 2020, 177, 112857. [Google Scholar] [CrossRef] [PubMed]
- Biesemeier, A.; Yoeruek, E.; Eibl, O.; Schraermeyer, U. Iron accumulation in Bruch’s membrane and melanosomes of donor eyes with age-related macular degeneration. Exp. Eye Res. 2015, 137, 39–49. [Google Scholar] [CrossRef] [PubMed]
- Jünemann, M.G.A.; Stopa, P.; Michalke, B.; Chaudhri, A.; Reulbach, U.; Huchzermeyer, C.; Schlötzer-Schrehardt, U.; Kruse, E.F.; Zrenner, E.; Rejdak, R. Levels of Aqueous Humor Trace Elements in Patients with Non-Exsudative Age-related Macular Degeneration: A Case-control Study. PLoS ONE 2013, 8, e56734. [Google Scholar] [CrossRef]
- Aberami, S.; Nikhalashree, S.; Bharathselvi, M.; Biswas, J.; Sulochana, N.K.; Coral, K. Elemental concentrations in Choroid-RPE and retina of human eyes with age-related macular degeneration. Exp. Eye Res. 2019, 186, 107718. [Google Scholar] [CrossRef] [PubMed]
- Erie, C.J.; Good, A.J.; Butz, J.A. Excess Lead in the Neural Retina in Age-Related Macular Degeneration. Am. J. Ophthalmol. 2009, 148, 890–894. [Google Scholar] [CrossRef] [PubMed]
- Rodríguez-Menéndez, S.; Fernández, B.; García, M.; Álvarez, L.; Luisa Fernández, M.; Sanz-Medel, A.; Coca-Prados, M.; Pereiro, R.; González-Iglesias, H. Quantitative study of zinc and metallothioneins in the human retina and RPE cells by mass spectrometry-based methodologies. Talanta 2018, 178, 222–230. [Google Scholar] [CrossRef] [PubMed]
- Gibbons, L.; Ozaki, E.; Greene, C.; Trappe, A.; Carty, M.; Coppinger, A.J.; Bowie, G.A.; Campbell, M.; Doyle, S.L. SARM1 Promotes Photoreceptor Degeneration in an Oxidative Stress Model of Retinal Degeneration. Front. Neurosci. 2022, 16, 852114. [Google Scholar] [CrossRef] [PubMed]
- Capelo-Martínez, J. Emerging Sample Treatments in Proteomics; Springer International Publishing AG: Cham, Switzerland, 2019. [Google Scholar]
- Norris, L.J.; Caprioli, R.M. Analysis of Tissue Specimens by Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry in Biological and Clinical Research. Chem. Rev. 2013, 113, 2309–2342. [Google Scholar] [CrossRef] [Green Version]
- Chughtai, K.; Heeren, R.M.A. Mass Spectrometric Imaging for Biomedical Tissue Analysis. Chem. Rev. 2010, 110, 3237–3277. [Google Scholar] [CrossRef] [Green Version]
- Sasaki, Y.; Kakita, H.; Kubota, S.; Sene, A.; Lee, J.T.; Ban, N.; Dong, Z.; Lin, B.J.; Boye, L.S.; DiAntonio, A.; et al. SARM1 depletion rescues NMNAT1-dependent photoreceptor cell death and retinal degeneration. eLife 2020, 9, e62027. [Google Scholar] [CrossRef]
- Ozaki, E.; Gibbons, L.; Neto, G.N.; Kenna, P.; Carty, M.; Humphries, M.; Humphries, P.; Campbell, M.; Monaghan, M.; Bowie, A.; et al. SARM1 deficiency promotes rod and cone photoreceptor cell survival in a model of retinal degeneration. Life Sci. Alliance 2020, 3, e201900618. [Google Scholar] [CrossRef] [PubMed]
- Aydin, E.; Cumurcu, T.; Ozugurlu, F.; Ozyurt, H.; Sahinoglu, S.; Mendil, D.; Hasdemir, E. Levels of iron, zinc, and copper in aqueous humor, lens, and serum in nondiabetic and diabetic patients: Their relation to cataract. Biol. Trace Elem. Res. 2005, 108, 33–41. [Google Scholar] [CrossRef] [PubMed]
- Limbeck, A.; Galler, P.; Bonta, M.; Bauer, G.; Nischkauer, W.; Vanhaecke, F. Recent advances in quantitative LA-ICP-MS analysis: Challenges and solutions in the life sciences and environmental chemistry. Anal. Bioanal. Chem. 2015, 407, 6593–6617. [Google Scholar] [CrossRef] [PubMed]
- Šala, M.; Šelih, S.V.; van Elteren, J.T. Gelatin gels as multi-element calibration standards in LA-ICP-MS bioimaging: Fabrication of homogeneous standards and microhomogeneity testing. Analyst 2017, 142, 3356–3359. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Doble, A.P.; de Vega, G.R.; Bishop, P.D.; Hare, J.D.; Clases, D. Laser Ablation–Inductively Coupled Plasma–Mass Spectrometry Imaging in Biology. Chem. Rev. 2021, 121, 11769–11822. [Google Scholar] [CrossRef]
- Volland, S.; Esteve-Rudd, J.; Hoo, J.; Yee, C.; Williams, D.S. A comparison of some organizational characteristics of the mouse central retina and the human macula. PLoS ONE 2015, 10, e0125631. [Google Scholar] [CrossRef] [Green Version]
- Elizabeth Rakoczy, P.; Yu, T.J.M.; Nusinowitz, S.; Chang, B.; Heckenlively, J.R. Mouse models of age-related macular degeneration. Exp. Eye Res. 2006, 82, 741–752. [Google Scholar] [CrossRef]
ID | ppm | mexp | mcalc | Position | No. of Missed Cleavages |
---|---|---|---|---|---|
Histone H32 | 2.51 | 1032.5975 | 1032.5949 | 42–50 | 0 |
Lens crystallin | 3.02 | 1255.5487 | 1255.5429 | 835–845 | 0 |
SARM1 | 1.12 | 1606.8428 | 1606.8410 | 202–216 | 0 |
Leptin | 1.44 | 1729.9963 | 1729.9938 | 27–41 | 2 |
Element | CMC | Gelatin (5%) | Gelatin (10%) |
---|---|---|---|
63Cu | 0.9574 | 0.9776 | 0.9939 |
66Zn | 0.9438 | 0.9696 | 0.9637 |
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Millar, J.; Ozaki, E.; Campbell, S.; Duckett, C.; Doyle, S.; Cole, L.M. Multiomic Mass Spectrometry Imaging to Advance Future Pathological Understanding of Ocular Disease. Metabolites 2022, 12, 1239. https://doi.org/10.3390/metabo12121239
Millar J, Ozaki E, Campbell S, Duckett C, Doyle S, Cole LM. Multiomic Mass Spectrometry Imaging to Advance Future Pathological Understanding of Ocular Disease. Metabolites. 2022; 12(12):1239. https://doi.org/10.3390/metabo12121239
Chicago/Turabian StyleMillar, Joshua, Ema Ozaki, Susan Campbell, Catherine Duckett, Sarah Doyle, and Laura M. Cole. 2022. "Multiomic Mass Spectrometry Imaging to Advance Future Pathological Understanding of Ocular Disease" Metabolites 12, no. 12: 1239. https://doi.org/10.3390/metabo12121239