SDPR expression in human trabecular meshwork and its potential role in racial disparities of glaucoma.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
04 May 2024
Historique:
received: 18 10 2023
accepted: 30 04 2024
medline: 5 5 2024
pubmed: 5 5 2024
entrez: 4 5 2024
Statut: epublish

Résumé

In order to identify how differential gene expression in the trabecular meshwork (TM) contributes to racial disparities of caveolar protein expression, TM dysfunction and development of primary open angle glaucoma (POAG), RNA sequencing was performed to compare TM tissue obtained from White and Black POAG surgical (trabeculectomy) specimens. Healthy donor TM tissue from White and Black donors was analyzed by PCR, qPCR, immunohistochemistry staining, and Western blot to evaluate SDPR (serum deprivation protein response; Cavin 2) and CAV1/CAV2 (Caveolin 1/Caveolin 2). Standard transmission electron microscopy (TEM) and immunogold labeled studies were performed. RNA sequencing demonstrated reduced SDPR expression in TM from Black vs White POAG patients' surgical specimens, with no significant expression differences in other caveolae-associated genes, confirmed by qPCR analysis. No racial differences in SDPR gene expression were noted in healthy donor tissue by PCR analysis, but there was greater expression as compared to specimens from patients with glaucoma. Analysis of SDPR protein expression confirmed specific expression in the TM regions, but not in adjacent tissues. TEM studies of TM specimens from healthy donors did not demonstrate any racial differences in caveolar morphology, but a significant reduction of caveolae with normal morphology and immuno-gold staining of SDPR were noted in glaucomatous TM as compared to TM from healthy donors. Linkage of SDPR expression levels in TM, POAG development, and caveolar ultrastructural morphology may provide the basis for a novel pathway of exploration of the pathologic mechanisms of glaucoma. Differential gene expression of SDPR in TM from Black vs White subjects with glaucoma may further our understanding of the important public health implications of the racial disparities of this blinding disease.

Identifiants

pubmed: 38704467
doi: 10.1038/s41598-024-61071-w
pii: 10.1038/s41598-024-61071-w
doi:

Substances chimiques

Caveolin 1 0
Caveolin 2 0
CAV1 protein, human 0
CAV2 protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

10258

Subventions

Organisme : NEI NIH HHS
ID : R21EY030618
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY02687
Pays : United States

Informations de copyright

© 2024. The Author(s).

Références

Tielsch, J. M. et al. Racial variations in the prevalence of primary open-angle glaucoma. The Baltimore Eye Survey. JAMA 266, 369–374 (1991).
doi: 10.1001/jama.1991.03470030069026 pubmed: 2056646
Kosoko-Lasaki, O., Gong, G., Haynatzki, G. & Wilson, M. R. Race, ethnicity and prevalence of primary open-angle glaucoma. J. Natl. Med. Assoc. 98, 1626–1629 (2006).
pubmed: 17052053 pmcid: 2569759
Wilson, R., Richardson, T. M., Hertzmark, E. & Grant, W. M. Race as a risk factor for progressive glaucomatous damage. Ann. Ophthalmol. 17, 653–659 (1985).
pubmed: 4073724
Friedman, D. S. et al. Prevalence of open-angle glaucoma among adults in the United States. Arch Ophthalmol.-Chic 122, 532–538 (2004).
doi: 10.1001/archopht.122.4.532
Thorleifsson, G. et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat. Genet. 42, 906–909 (2010).
doi: 10.1038/ng.661 pubmed: 20835238 pmcid: 3222888
Wiggs, J. L. et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma in Caucasians from the USA. Hum. Mol. Genet. 20, 4707–4713 (2011).
doi: 10.1093/hmg/ddr382 pubmed: 21873608 pmcid: 3209825
Kuehn, M. H. et al. Chromosome 7q31 POAG locus: ocular expression of caveolins and lack of association with POAG in a US cohort. Mol. Vision 17, 430–435 (2011).
Marian, A. J. Molecular genetic studies of complex phenotypes. Transl. Res. 159, 64–79 (2012).
doi: 10.1016/j.trsl.2011.08.001 pubmed: 22243791
Pronin, S., Brown, L., Megaw, R. & Tatham, A.J. Measurement of intraocular pressure by patients with glaucoma. JAMA Ophthalmol. 135, 1030–1036 (2017).
Chan, T. C. W., Bala, C., Siu, A., Wan, F. & White, A. Risk factors for rapid glaucoma disease progression. Am. J. Ophthalmol. 180, 151–157 (2017).
doi: 10.1016/j.ajo.2017.06.003 pubmed: 28624324
Stamer, W. D. & Acott, T. S. Current understanding of conventional outflow dysfunction in glaucoma. Curr. Opin. Ophthalmol. 23, 135–143 (2012).
doi: 10.1097/ICU.0b013e32834ff23e pubmed: 22262082 pmcid: 3770936
Palade, G. E. An electron microscope study of the mitochondrial structure. J. Histochem. Cytochem. 1, 188–211 (1953).
doi: 10.1177/1.4.188 pubmed: 13069686
Yamada, E. The fine structure of the gall bladder epithelium of the mouse. J. Biophys. Biochem. Cytol. 1, 445–458 (1955).
doi: 10.1083/jcb.1.5.445 pubmed: 13263332 pmcid: 2229656
Busija, A. R., Patel, H. H. & Insel, P. A. Caveolins and cavins in the trafficking, maturation, and degradation of caveolae: Implications for cell physiology. Am. J. Physiol. -Cell Ph. 312, C459–C477 (2017).
doi: 10.1152/ajpcell.00355.2016
Gu, X., Reagan, A. M., McClellan, M. E. & Elliott, M. H. Caveolins and caveolae in ocular physiology and pathophysiology. Prog. Retin Eye Res. 56, 84–106 (2017).
doi: 10.1016/j.preteyeres.2016.09.005 pubmed: 27664379
Tamm, E. R. The trabecular meshwork outflow pathways: Structural and functional aspects. Exp. Eye Res. 88, 648–655 (2009).
doi: 10.1016/j.exer.2009.02.007 pubmed: 19239914
Herrnberger, L., Ebner, K., Junglas, B. & Tamm, E. R. The role of plasmalemma vesicle-associated protein (PLVAP) in endothelial cells of Schlemm’s canal and ocular capillaries. Exp. Eye Res. 105, 27–33 (2012).
doi: 10.1016/j.exer.2012.09.011 pubmed: 23063469
Yu, J. et al. Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels. J. Clin. Invest. 116, 1284–1291 (2006).
doi: 10.1172/JCI27100 pubmed: 16670769 pmcid: 1451207
Patel, H. H., Murray, F. & Insel, P. A. Caveolae as organizers of pharmacologically relevant signal transduction molecules. Annu. Rev. Pharmacol. 48, 359–391 (2008).
doi: 10.1146/annurev.pharmtox.48.121506.124841
Sowa, G. Caveolae, caveolins, cavins, and endothelial cell function: New insights. Front. Physiol. 2, 120 (2012).
doi: 10.3389/fphys.2011.00120 pubmed: 22232608 pmcid: 3252561
Hansen, C. G., Bright, N. A., Howard, G. & Nichols, B. J. SDPR induces membrane curvature and functions in the formation of caveolae. Nat. Cell Biol. 11, 807–814 (2009).
doi: 10.1038/ncb1887 pubmed: 19525939 pmcid: 2712677
Elliott, M. H. et al. Caveolin-1 modulates intraocular pressure: Implications for caveolae mechanoprotection in glaucoma. Sci. Rep. 6, 37127 (2016).
doi: 10.1038/srep37127 pubmed: 27841369 pmcid: 5107904
De Ieso, M. L. et al. Physiologic Consequences of caveolin-1 ablation in conventional outflow endothelia. Invest. Ophthalmol. Vis. Sci. 61, 32 (2020).
doi: 10.1167/iovs.61.11.32 pubmed: 32940661 pmcid: 7500130
Yazar, S. & Mackey, D. A. Counting on caveolin for clues in glaucoma. Clin. Exp. Ophthalmol. 42, 511–512 (2014).
doi: 10.1111/ceo.12394 pubmed: 25146306
Gratton, J. P., Bernatchez, P. & Sessa, W. C. Caveolae and caveolins in the cardiovascular system. Circ. Res. 94, 1408–1417 (2004).
doi: 10.1161/01.RES.0000129178.56294.17 pubmed: 15192036
Cohen, A. W., Hnasko, R., Schubert, W. & Lisanti, M. P. Role of caveolae and caveolins in health and disease. Physiol. Rev. 84, 1341–1379 (2004).
doi: 10.1152/physrev.00046.2003 pubmed: 15383654
Hodapp E, P.R.I., Anderson DR. Book: Clinical Decisions in Glaucoma. (The CV Mosby Co, 1993).
Nabi, I. R. Cavin fever: Regulating caveolae. Nat. Cell Biol. 11, 789–791 (2009).
doi: 10.1038/ncb0709-789 pubmed: 19568263
Quest, A. F., Gutierrez-Pajares, J. L. & Torres, V. A. Caveolin-1: An ambiguous partner in cell signalling and cancer. J. Cell Mol. Med. 12, 1130–1150 (2008).
doi: 10.1111/j.1582-4934.2008.00331.x pubmed: 18400052 pmcid: 3865655
Koussounadis, A., Langdon, S.P., Um, I.H., Harrison, D.J. & Smith, V.A. Relationship between differentially expressed mRNA and mRNA-protein correlations in a xenograft model system. Sci. Rep.-Uk 5, 10775 (2015).
Liu, Y., Beyer, A. & Aebersold, R. On the dependency of cellular protein levels on mRNA abundance. Cell 165, 535–550 (2016).
doi: 10.1016/j.cell.2016.03.014 pubmed: 27104977
Stamer, W. D. et al. Biomechanics of Schlemm’s canal endothelium and intraocular pressure reduction. Prog. Retin. Eye Res. 44, 86–98 (2015).
doi: 10.1016/j.preteyeres.2014.08.002 pubmed: 25223880
Overby, D. R. et al. Altered mechanobiology of Schlemm’s canal endothelial cells in glaucoma. Proc. Natl. Acad. Sci. USA 111, 13876–13881 (2014).
doi: 10.1073/pnas.1410602111 pubmed: 25201985 pmcid: 4183270
Inomata, H., Bill, A. & Smelser, G. K. Aqueous humor pathways through the trabecular meshwork and into Schlemm’s canal in the cynomolgus monkey (Macaca irus). An electron microscopic study. Am. J. Ophthalmol. 73, 760–789 (1972).
doi: 10.1016/0002-9394(72)90394-7 pubmed: 4623937
Sabanay, I., Gabelt, B. T., Tian, B., Kaufman, P. L. & Geiger, B. H-7 effects on the structure and fluid conductance of monkey trabecular meshwork. Arch Ophthalmol. 118, 955–962 (2000).
pubmed: 10900110
Cookson, W., Liang, L., Abecasis, G., Moffatt, M. & Lathrop, M. Mapping complex disease traits with global gene expression. Nat. Rev. Genet. 10, 184–194 (2009).
doi: 10.1038/nrg2537 pubmed: 19223927 pmcid: 4550035
Huber, W. G., Becker, S. R. & Archer, B. P. Bioavailability of residues—Current status. J. Environ. Pathol. Tox. 3, 45–63 (1980).
Petrini, C. Ethical and legal considerations regarding the ownership and commercial use of human biological materials and their derivatives. J. Blood Med. 3, 87–96 (2012).
doi: 10.2147/JBM.S36134 pubmed: 22977316 pmcid: 3440234
Mersha, T. B. & Abebe, T. Self-reported race/ethnicity in the age of genomic research: Its potential impact on understanding health disparities. Hum. Genom. 9, 1 (2015).
doi: 10.1186/s40246-014-0023-x
Keller, K. E. et al. Consensus recommendations for trabecular meshwork cell isolation, characterization and culture. Exp. Eye Res. 171, 164–173 (2018).
doi: 10.1016/j.exer.2018.03.001 pubmed: 29526795 pmcid: 6042513
Stamer, W. D. & Clark, A. F. The many faces of the trabecular meshwork cell. Exp. Eye Res. 158, 112–123 (2017).
doi: 10.1016/j.exer.2016.07.009 pubmed: 27443500
Ma, N. et al. Expression profiling of ascorbic acid-related transporters in human and mouse eyes (vol 57, pg 3440, 2016). Invest. Ophth. Vis. Sci. 57, 3927–3927 (2016).

Auteurs

Ying-Bo Shui (YB)

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Ying Liu (Y)

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Andrew J W Huang (AJW)

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, 63110, USA.

Carla J Siegfried (CJ)

Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO, 63110, USA. siegfried@wustl.edu.

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