The influence of path length and matrix components on ageing characteristics of transport between the choroid and the outer retina
Abstract
PURPOSE: To determine the relative influence of path length and matrix components on the movement of small solutes and water between the choroid and the outer retina. METHODS: Human and bovine Bruch's membrane-choroid (BC) tissue samples were mounted in modified Ussing chambers, and the diffusion of taurine and hydraulic conductivity (Lp) was determined. In humans, diffusion of taurine was determined as a function of age of the donor. The relative contribution of Bruch's membrane in the BC complex to transport processes was measured after its removal by laser ablation. Similarly, the effect of choroidal path length was determined. In humans, tracking the trend of age-related thinning provided samples of various path lengths. In young bovine animals (< or =2 years old), choroidal thickness was adjusted by laser ablation. RESULTS: Diffusion of taurine across human BC decreased linearly from 162.7 to 105.9 nanomoles/h per 3 mm between 10 and 90 years of age (P < 0.05). Ablation of Bruch's membrane increased diffusion of taurine from 129 to 287.9 nanomoles/h per 4 mm in human (donor age 55, 74, and 82 years; P < 0.005) but caused no statistically significant change in bovine BC. Diffusion of taurine across bovine BC was greater in samples with partially ablated choroid (218 nanomoles/h per 4 mm) than in normal control samples (128.75 nanomoles/h per 4 mm). Lp was not measurable in bovine samples after complete ablation of Bruch's membrane, but did not change significantly as the choroid thinned. CONCLUSIONS: The data suggest that both path length and matrix components contribute to the decline of diffusion of small solutes across BC with age. The importance of matrix components was also demonstrated in restricting the movement of water while choroidal thickness played little if any role.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The movement of water across BrM, as measured with Ussing chambers, decreases with age.
“The movement of water across BrM, as measured with Ussing chambers [60,61,62,63], decreases with age.”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [63]
Cites
Age-Related Macular Degeneration and Blindness due to Neovascular Maculopathy
Ferris, F. L., Fine, S., & Hyman, L. (1984) · Archives of Ophthalmology · doi:10.1001/archopht.1984.01040031330019 · Cited by 1,097 · see citing works
Morphometric analysis of Bruch's membrane, the choriocapillaris, and the choroid in aging.
Ramrattan, R. S., van der Schaft, T. L., Mooy, C. M., de Bruijn, W. C., Mulder, P. G. H., & de Jong, P. T. (1994) · PubMed · Cited by 744 · see citing works
Aging changes in Bruch's membrane. A histochemical and morphologic study.
Pauleikhoff, D., Harper, C. A., Marshall, J., & Bird, A. C. (1990) · PubMed · Cited by 401 · see citing works
Turnell, D. C., & Cooper, J. D. (1982) · Clinical Chemistry · doi:10.1093/clinchem/28.3.527 · Cited by 363 · see citing works
Age-related variation in the hydraulic conductivity of Bruch's membrane.
Moore, D., Hussain, A., & Marshall, J. (1995) · PubMed · Cited by 288 · see citing works
Sarks, S. H., Arnold, J. J., Killingsworth, M. C., & Sarks, J. P. (1999) · British Journal of Ophthalmology · doi:10.1136/bjo.83.3.358 · Cited by 269 · see citing works
Increase in the advanced glycation end product pentosidine in Bruch's membrane with age.
Handa, J. T., Verzijl, N., Matsunaga, H., Aotaki-Keen, A. E., Lutty, G. A., Koppele, J. M. T., Miyata, T., & Hjelmeland, L. M. (1999) · PubMed · Cited by 237 · see citing works
Oxygen distribution in the macaque retina.
Ahmed, J., Braun, R. D., Dunn, R., & Linsenmeier, R. A. (1993) · PubMed · Cited by 220 · see citing works
The interpretation of optical coherence tomography images of the retina.
Chauhan, D. S., & Marshall, J. A. (1999) · PubMed · Cited by 202 · see citing works
Retinal pigment epithelial detachments in the elderly.
Bird, A. C., & Marshall, J. (1986) · PubMed · Cited by 191 · see citing works
The retinal pigment epithelium : function and disease
Marmor, M. F., & Wolfensberger, T. J. (1998) · Cited by 185 · see citing works
Hydrodynamics of ageing Bruch’s membrane: Implications for macular disease
STARITA, C., HUSSAIN, A. A., PAGLIARINI, S., & MARSHALL, J. (1996) · Experimental Eye Research · doi:10.1006/exer.1996.0066 · Cited by 170 · see citing works
The effect of age on the macromolecular permeability of human Bruch's membrane.
Moore, D., & Clover, G. M. (2001) · PubMed · Cited by 142 · see citing works
Preparation of Bruch's membrane and analysis of the age-related changes in the structural collagens.
KARWATOWSKI, W. S. S., Jeffries, T. E., Duance, V. C., Albon, J., Bailey, A. J., & Easty, D. L. (1995) · British Journal of Ophthalmology · doi:10.1136/bjo.79.10.944 · Cited by 141 · see citing works
Localization of the site of major resistance to fluid transport in Bruch's membrane.
Starita, C., Hussain, A. A., Patmore, A., & Marshall, J. (1997) · PubMed · Cited by 113 · see citing works
Bruch's membrane change with age.
Bird, A. C. (1992) · British Journal of Ophthalmology · doi:10.1136/bjo.76.3.166 · Cited by 112 · see citing works
Is Basal Laminar Deposit Unique for Age-Related Macular Degeneration?
van der Schaft, T. L. (1991) · Archives of Ophthalmology · doi:10.1001/archopht.1991.01080030122052 · Cited by 108 · see citing works
Bruch’s membrane age-related changes vary by region
Newsome, D. A., Huh, W., & Green, W. R. (1987) · Current Eye Research · doi:10.3109/02713688709025231 · Cited by 105 · see citing works
Hussain, A. A., Rowe, L., & Marshall, J. (2002) · Journal of the Optical Society of America A · doi:10.1364/josaa.19.000166 · Cited by 77 · see citing works
ITO, Y. N., Mori, K., YOUNG-DUVALL, J., & Yoneya, S. (2001) · Retina · doi:10.1097/00006982-200106000-00007 · Cited by 60 · see citing works
Lyda, W., Eriksen, N., & Krishna, N. (1957) · American Journal of Ophthalmology · doi:10.1016/0002-9394(57)93133-1 · Cited by 28 · see citing works
Microablation of Choroidal Tissue from Bruch's Membrane using a 193nm Excimer Laser
Schütt, F., & Holz, F. G. (2002) · Experimental Eye Research · doi:10.1006/exer.2001.1102 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Review: taurine: a "very essential" amino acid.
Ripps, H., & Shen, W. (2012) · Europe PMC (PubMed Central) · Cited by 583 · see citing works
The dynamic nature of Bruch's membrane
Booij, J. C., Baas, D. C., Beisekeeva, J., Gorgels, T. G. M. F., & Bergen, A. A. B. (2010) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.08.003 · Cited by 581 · see citing works
Transplantation of the RPE in AMD
Binder, S., Stanzel, B. V., Krebs, I., & Glittenberg, C. G. (2007) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2007.02.002 · Cited by 292 · see citing works
Sarks, S., Cherepanoff, S., Killingsworth, M., & Sarks, J. (2007) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.06-0443 · Cited by 244 · see citing works
RPE transplantation and its role in retinal disease
da Cruz, L., Chen, F. K., Ahmado, A., Greenwood, J., & Coffey, P. J. (2007) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2007.07.001 · Cited by 238 · see citing works
Fields, M. A., Priore, L. V. D., Adelman, R. A., & Rizzolo, L. J. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.100803 · Cited by 172 · see citing works
Transport Barriers in Transscleral Drug Delivery for Retinal Diseases
Kim, S. H., Lutz, R. J., Wang, N. S., & Robinson, M. R. (2007) · Ophthalmic Research · doi:10.1159/000108117 · Cited by 173 · see citing works
Age-related macular degeneration and changes in the extracellular matrix
Romaniuk, W. (2014) · Medical Science Monitor · doi:10.12659/msm.889887 · Cited by 116 · see citing works
Thin collagen film scaffolds for retinal epithelial cell culture
Lu, J. T., Lee, C., Bent, S. F., Fishman, H. A., & Sabelman, E. E. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.11.023 · Cited by 114 · see citing works
Fleckenstein, M., Schmitz-Valckenberg, S., Martens, C., Kosanetzky, S., Brinkmann, C. K., Hageman, G. S., & Holz, F. G. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-7021 · Cited by 106 · see citing works
Cheruvu, N. P. S., & Kompella, U. B. (2006) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0404 · Cited by 107 · see citing works
Proline mediates metabolic communication between retinal pigment epithelial cells and the retina
Yam, M., Engel, A. L., Wang, Y., Zhu, S., Hauer, A., Zhang, R., Lohner, D., Huang, J., Dinterman, M., Zhao, C., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.007983 · Cited by 89 · see citing works
Koss, M., Falabella, P., Stefanini, F. R., Pfister, M., Thomas, B. B., Kashani, A. H., Brant, R., Zhu, D., Clegg, D., Hinton, D. R., et al. (2016) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-016-3386-y · Cited by 89 · see citing works
Lee, C., Vroom, J. A., Fishman, H. A., & Bent, S. F. (2005) · Biomaterials · doi:10.1016/j.biomaterials.2005.09.008 · Cited by 79 · see citing works
Moussa, K., Lee, J. Y., Stinnett, S. S., & Jaffe, G. J. (2013) · Retina · doi:10.1097/iae.0b013e31828d6052 · Cited by 71 · see citing works
Evaluation of Choroidal Thickness Using Optical Coherent Tomography: A Review
Xie, R., Qiu, B., Chhablani, J. K., & Zhang, X. (2021) · Frontiers in Medicine · doi:10.3389/fmed.2021.783519 · Cited by 69 · see citing works
Depot formulations to sustain periocular drug delivery to the posterior eye segment
Agban, Y., Thakur, S. S., Mugisho, O. O., & Rupenthal, I. D. (2019) · Drug Discovery Today · doi:10.1016/j.drudis.2019.03.023 · Cited by 57 · see citing works
Treumer, F., Klettner, A., Baltz, J., Hussain, A. A., Miura, Y., Brinkmann, R., Roider, J., & Hillenkamp, J. (2012) · Experimental Eye Research · doi:10.1016/j.exer.2012.02.011 · Cited by 54 · see citing works
Self-citationPosterior Drug Delivery Via Periocular route: Challenges and Opportunities
Waite, D. T., Wang, Y., Jones, D. S., Stitt, A. W., & Singh, T. R. R. (2017) · Therapeutic Delivery · doi:10.4155/tde-2017-0097 · Cited by 54 · see citing works
Richert, E., Koinzer, S., Tode, J., Schlott, K., Brinkmann, R., Hillenkamp, J., Klettner, A., & Roider, J. B. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-23163 · Cited by 47 · see citing works
Self-citationThe Diverse Roles of TIMP-3: Insights into Degenerative Diseases of the Senescent Retina and Brain
Dewing, J. M., Carare, R. O., Lotery, A. J., & Ratnayaka, J. A. (2019) · Cells · doi:10.3390/cells9010039 · Cited by 46 · see citing works
Hammadi, S., Tzoumas, N., Ferrara, M., Meschede, I. P., Lo, K., Harris, C., Lako, M., & Steel, D. H. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12082870 · Cited by 44 · see citing works
Sustained transscleral drug delivery
Barocas, V. H., & Balachandran, R. K. (2007) · Expert Opinion on Drug Delivery · doi:10.1517/17425247.5.1.1 · Cited by 42 · see citing works
Passage of low-density lipoproteins through Bruch’s membrane and choroid
Cankova, Z., Huang, J.-D., Kruth, H. S., & Johnson, M. (2011) · Experimental Eye Research · doi:10.1016/j.exer.2011.10.016 · Cited by 43 · see citing works
Cholesterol-poly(ethylene) glycol nanocarriers for the transscleral delivery of sirolimus
Elsaid, N., Somavarapu, S., & Jackson, T. L. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.02.001 · Cited by 39 · see citing works
Hillenkamp, J., Hussain, A. A., Jackson, T. L., Cunningham, J. R., & Marshall, J. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-0919 · Cited by 34 · see citing works
Self-citationQuerques, G., Guigui, B., Leveziel, N., Querques, L., COSCAS, G. J., Soubrane, G., & Souied, E. H. (2011) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-011-1702-0 · Cited by 31 · see citing works
Paik, D. C., Saito, L. Y., Sugirtharaj, D. D., & Holmes, J. W. (2006) · Connective Tissue Research · doi:10.1080/03008200600721569 · Cited by 27 · see citing works
RETINAL VASCULAR ABNORMALITIES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Jackson, T. L., Danis, R. P., Goldbaum, M., Slakter, J. S., Shusterman, E. M., O’Shaughnessy, D., & Moshfeghi, D. M. (2013) · Retina · doi:10.1097/iae.0b013e3182a487be · Cited by 19 · see citing works
Aging of the Retinal Pigment Epithelium
Boulton, M. E. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-374-5_19 · Cited by 19 · see citing works
Compartmental Analysis of Taurine Transport to the Outer Retina in the Bovine Eye
Hillenkamp, J., Hussain, A. A., Jackson, T. L., Constable, P. A., Cunningham, J. R., & Marshall, J. (2004) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-0624 · Cited by 19 · see citing works
Self-citationRickabaugh, E., Weatherston, D., Harris, T. I., Jones, J. A., & Vargis, E. (2023) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.3c00411 · Cited by 11 · see citing works
Age Changes in Bruch's Membrane and Related Structures
Guymer, R. H., & Bird, A. C. (2006) · Elsevier eBooks · doi:10.1016/b978-0-323-02598-0.50065-3 · Cited by 10 · see citing works
Effects of Hypercholesterolaemia in the Retina
Trivio, A., De, R., Rojas, B., Gallego, B., Ramrez, A. I., Salazar, J. J., & Ramrez, J. M. (2012) · InTech eBooks · doi:10.5772/48359 · Cited by 10 · see citing works
Richert, E., Papenkort, J., Klettner, A., Tode, J., Koinzer, S., Brinkmann, R., Fink, C., Roeder, T., Lucius, R., & Roider, J. B. (2020) · Lasers in Surgery and Medicine · doi:10.1002/lsm.23288 · Cited by 8 · see citing works
Chronologic versus Biologic Aging of the Human Choroid
May, C. A. (2013) · The Scientific World JOURNAL · doi:10.1155/2013/378206 · Cited by 8 · see citing works
Romaniuk, D. (2014) · Medical Science Monitor · doi:10.12659/msm.890031 · Cited by 7 · see citing works
Extracellular Matrix: The Unexplored Aspects of Retinal Pathologies and Regeneration
Serjanov, D., & Hyde, D. R. (2023) · Advances in experimental medicine and biology · doi:10.1007/978-3-031-27681-1_45 · Cited by 5 · see citing works
Lim, P. C., & Layton, C. J. (2015) · Clinical and Experimental Ophthalmology · doi:10.1111/ceo.12671 · Cited by 4 · see citing works
Mainster, M. A., & Boulton, M. E. (2008) · Elsevier eBooks · doi:10.1016/b978-1-4160-0016-7.50177-6 · Cited by 3 · see citing works
Fibrogliosis in neovascular age-related macular degeneration: A new mechanistic perspective
Merle, D. A., Beretta, F., Sacconi, R., & Querques, G. (2025) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2025.09.019 · Cited by 2 · see citing works
Sundstrom, J. M., Weber, S. R., Zhou, M., & Hogan, R. N. (2022) · Springer eBooks · doi:10.1007/978-3-030-42634-7_305 · Cited by 2 · see citing works
Drug Delivery to the Posterior Eye Using Etched Microneedles
Mahadevan, G. (2011) · MacSphere (McMaster University) · doi:10.71548/15650
Age-related macular degeneration: histopathological and serum autoantibody studies
Cherepanoff, S. (2007) · The Sydney eScholarship Repository (The University of Sydney)
Function and pathology of the human retinal pigment epithelium
Booij, J. C. (2010) · UvA-DARE (University of Amsterdam)
Hogan, R. N. (2008) · Elsevier eBooks · doi:10.1016/b978-1-4160-0016-7.50340-4
Sundstrom, J. M., Weber, S. R., Zhou, M., & Hogan, R. N. (2021) · Springer eBooks · doi:10.1007/978-3-319-90495-5_305-1
Skalicky, S. E. (2015) · Springer eBooks · doi:10.1007/978-981-287-846-5_11
- Authors
- Hillenkamp, J.
- Affiliations
- St Thomas' Hospital (GB)
- Corresponding author
- Hillenkamp, J.
- ORCID
- Hillenkamp, J.
- Venue
- Investigative Ophthalmology & Visual Science
- Published
- 2004-05-01
- Volume
- 45
- Issue
- 5
- Pages
- 1493-1498
- ISSN
- 0146-0404 (ISSN-L)
- OpenAlex
- W2089111199
- Cited by
- 49
- References
- 22
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 4.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- choroid, outer retina, Bruch's membrane, choroidal thickness, age-related decline, hydraulic conductivity, age-related macular degeneration, solute transport
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Animals, Biological Transport, Body Water, Cattle, Cell Membrane Permeability, Child, Choroid, Chromatography, High Pressure Liquid, Diffusion, Humans, Middle Aged, Retina, Taurine, Bruch Membrane, Laser Coagulation, Tomography, Optical Coherence
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
