Characterization of Calcium Phosphate Spherical Particles in the Subretinal Pigment Epithelium–Basal Lamina Space in Aged Human Eyes
Purpose: Micrometer-sized spherules formed of hydroxyapatite or whitlockite were identified within extracellular deposits that accumulate in the space between the basal lamina (BL) of retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch’s membrane (sub-RPE–BL space). This invest...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-09-01
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| Series: | Ophthalmology Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666914521000518 |
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| author | Matthew G. Pilgrim, PhD Salma Marouf, MD Sarah Fearn, PhD Lajos Csincsik, PhD Elod Kortvely, PhD Jonathan C. Knowles, PhD Goldis Malek, PhD Richard B. Thompson, PhD Imre Lengyel, PhD |
| author_facet | Matthew G. Pilgrim, PhD Salma Marouf, MD Sarah Fearn, PhD Lajos Csincsik, PhD Elod Kortvely, PhD Jonathan C. Knowles, PhD Goldis Malek, PhD Richard B. Thompson, PhD Imre Lengyel, PhD |
| author_sort | Matthew G. Pilgrim, PhD |
| collection | DOAJ |
| description | Purpose: Micrometer-sized spherules formed of hydroxyapatite or whitlockite were identified within extracellular deposits that accumulate in the space between the basal lamina (BL) of retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch’s membrane (sub-RPE–BL space). This investigation aimed to characterize the morphologic features, structure, and distribution of these spherules in aged human eyes with and without clinical indications of age-related macular degeneration (AMD). Design: Experimental study. Participants: Five human eyes with varying degrees of sub-RPE–BL deposits were obtained from the University College London Institute of Ophthalmology and Moorfield’s Eye Hospital Tissue Repository or the Advancing Sight Network. Two eyes were reported as having clinical indications of AMD (age, 76–87 years), whereas 3 were considered healthy (age, 69–91 years). Methods: Cadaveric eyes with sub-RPE–BL deposits were embedded in paraffin wax and sectioned to a thickness of 4-10 μm. Spherules were identified and characterized using high-resolution scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy, and time-of-flight secondary ion mass spectroscopy. Main Outcome Measures: High-resolution scanning electron micrographs of spherules, the size-frequency distribution of spherules including average diameter, and the distribution of particles across the central-peripheral axis. Elemental maps and time-of-flight secondary ion mass spectra also were obtained. Results: The precipitation of spherules is ubiquitous across the central, mid-peripheral, and far-peripheral axis in aged human eyes. No significant difference was found in the frequency of spherules along this axis. However, statistical analysis indicated that spherules exhibited significantly different sizes in these regions. In-depth analysis revealed that spherules in the sub-RPE–BL space of eyes with clinical signs of AMD were significantly larger (median diameter, 1.64 μm) than those in healthy aged eyes (median diameter, 1.16 μm). Finally, spherules showed great variation in surface topography and internal structure. Conclusions: The precipitation of spherules in the sub-RPE–BL space is ubiquitous across the central–peripheral axis in aged human eyes. However, a marked difference exists in the size and frequency of spherules in eyes with clinical signs of AMD compared to those without, suggesting that the size and frequency of spherules may be associated with AMD. |
| first_indexed | 2024-12-17T22:55:59Z |
| format | Article |
| id | doaj.art-5d4a1161f14a4c1b8163b18581ad20aa |
| institution | Directory Open Access Journal |
| issn | 2666-9145 |
| language | English |
| last_indexed | 2024-12-17T22:55:59Z |
| publishDate | 2021-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ophthalmology Science |
| spelling | doaj.art-5d4a1161f14a4c1b8163b18581ad20aa2022-12-21T21:29:33ZengElsevierOphthalmology Science2666-91452021-09-0113100053Characterization of Calcium Phosphate Spherical Particles in the Subretinal Pigment Epithelium–Basal Lamina Space in Aged Human EyesMatthew G. Pilgrim, PhD0Salma Marouf, MD1Sarah Fearn, PhD2Lajos Csincsik, PhD3Elod Kortvely, PhD4Jonathan C. Knowles, PhD5Goldis Malek, PhD6Richard B. Thompson, PhD7Imre Lengyel, PhD8University College London Institute of Ophthalmology, London, United Kingdom; Division of Biomaterials and Tissue Engineering, University College London Eastman Dental Institute, Royal Free Hospital, London, United Kingdom; Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Belfast, United KingdomBarts and The London School of Medicine and Dentistry, London, United KingdomDepartment of Materials, Imperial College London, London, United KingdomCentre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Belfast, United KingdomRoche Pharma Research and Early Development, Immunology, Infectious Diseases and Ophthalmology (I20) Discovery and Translational Area, Roche Innovation Centre Basel, F. Hoffmann-La Roche, Ltd., Basel, SwitzerlandDivision of Biomaterials and Tissue Engineering, University College London Eastman Dental Institute, Royal Free Hospital, London, United KingdomDepartment of Ophthalmology, Albert Eye Research Institute, and Department of Pathology, Duke University School of Medicine, Durham, North CarolinaDepartment of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MarylandCentre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Science, Queen’s University Belfast, Belfast, United Kingdom; Correspondence: Imre Lengyel, PhD, Wellcome-Wolfson Institute for Experimental Medicine, Queen’s University Belfast, 97 Lisburn Road, Belfast, Northern Ireland, BT9 7BL, United Kingdom.Purpose: Micrometer-sized spherules formed of hydroxyapatite or whitlockite were identified within extracellular deposits that accumulate in the space between the basal lamina (BL) of retinal pigment epithelium (RPE) and the inner collagenous layer of Bruch’s membrane (sub-RPE–BL space). This investigation aimed to characterize the morphologic features, structure, and distribution of these spherules in aged human eyes with and without clinical indications of age-related macular degeneration (AMD). Design: Experimental study. Participants: Five human eyes with varying degrees of sub-RPE–BL deposits were obtained from the University College London Institute of Ophthalmology and Moorfield’s Eye Hospital Tissue Repository or the Advancing Sight Network. Two eyes were reported as having clinical indications of AMD (age, 76–87 years), whereas 3 were considered healthy (age, 69–91 years). Methods: Cadaveric eyes with sub-RPE–BL deposits were embedded in paraffin wax and sectioned to a thickness of 4-10 μm. Spherules were identified and characterized using high-resolution scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy, and time-of-flight secondary ion mass spectroscopy. Main Outcome Measures: High-resolution scanning electron micrographs of spherules, the size-frequency distribution of spherules including average diameter, and the distribution of particles across the central-peripheral axis. Elemental maps and time-of-flight secondary ion mass spectra also were obtained. Results: The precipitation of spherules is ubiquitous across the central, mid-peripheral, and far-peripheral axis in aged human eyes. No significant difference was found in the frequency of spherules along this axis. However, statistical analysis indicated that spherules exhibited significantly different sizes in these regions. In-depth analysis revealed that spherules in the sub-RPE–BL space of eyes with clinical signs of AMD were significantly larger (median diameter, 1.64 μm) than those in healthy aged eyes (median diameter, 1.16 μm). Finally, spherules showed great variation in surface topography and internal structure. Conclusions: The precipitation of spherules in the sub-RPE–BL space is ubiquitous across the central–peripheral axis in aged human eyes. However, a marked difference exists in the size and frequency of spherules in eyes with clinical signs of AMD compared to those without, suggesting that the size and frequency of spherules may be associated with AMD.http://www.sciencedirect.com/science/article/pii/S2666914521000518ChoroidDrusenEctopic calcificationRetinaSpherical particleSub–retinal pigment epithelium |
| spellingShingle | Matthew G. Pilgrim, PhD Salma Marouf, MD Sarah Fearn, PhD Lajos Csincsik, PhD Elod Kortvely, PhD Jonathan C. Knowles, PhD Goldis Malek, PhD Richard B. Thompson, PhD Imre Lengyel, PhD Characterization of Calcium Phosphate Spherical Particles in the Subretinal Pigment Epithelium–Basal Lamina Space in Aged Human Eyes Ophthalmology Science Choroid Drusen Ectopic calcification Retina Spherical particle Sub–retinal pigment epithelium |
| title | Characterization of Calcium Phosphate Spherical Particles in the Subretinal Pigment Epithelium–Basal Lamina Space in Aged Human Eyes |
| title_full | Characterization of Calcium Phosphate Spherical Particles in the Subretinal Pigment Epithelium–Basal Lamina Space in Aged Human Eyes |
| title_fullStr | Characterization of Calcium Phosphate Spherical Particles in the Subretinal Pigment Epithelium–Basal Lamina Space in Aged Human Eyes |
| title_full_unstemmed | Characterization of Calcium Phosphate Spherical Particles in the Subretinal Pigment Epithelium–Basal Lamina Space in Aged Human Eyes |
| title_short | Characterization of Calcium Phosphate Spherical Particles in the Subretinal Pigment Epithelium–Basal Lamina Space in Aged Human Eyes |
| title_sort | characterization of calcium phosphate spherical particles in the subretinal pigment epithelium basal lamina space in aged human eyes |
| topic | Choroid Drusen Ectopic calcification Retina Spherical particle Sub–retinal pigment epithelium |
| url | http://www.sciencedirect.com/science/article/pii/S2666914521000518 |
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