A comparative study on morphology of corneal endothelium and Descemet membrane, TGF-β1 aqueous humor level in Fuchs endothelial corneal dystrophy and pseudophakic bullous keratopathy
Yusef N. Yusef , Anastasia M. Subbot , Natalia V. Fisenko , Grigory A. Osipyan , Tatiana A. Demura
Genes & Cells ›› 2022, Vol. 17 ›› Issue (4) : 143 -152.
A comparative study on morphology of corneal endothelium and Descemet membrane, TGF-β1 aqueous humor level in Fuchs endothelial corneal dystrophy and pseudophakic bullous keratopathy
BACKGROUND: Chronic corneal edema is often associated with endothelial cell loss due to Fuchs endothelial dystrophy and pseudophakic bullous keratopathy.
AIM: to compare the changes of Descemet membrane/endothelium complexes and aqueous humor TGF-β1 level in Fuchs endothelial dystrophy and pseudophakic bullous keratopathy.
MATERIALS AND METODS: The study included 35 patients (36 eyes) with chronic corneal edema caused by irreversible dysfunction of endothelial cells: 1a group — 12 patients (12 eyes) with Fuchs endothelial dystrophy, 1b group — 10 patients (10 eyes) with pseudophakic bullous keratopathy; 2a group — 8 patients (9 eyes) with Fuchs endothelial dystrophy, 2b group — 5 patients (5 eyes) with pseudophakic bullous keratopathy. Control groups — 5 (for groups 1a, 1b) and 7 (for groups 2a, 2b) donor corneoscleral discs.
TGF-β1 level in patients of groups 1a, 1b was determined by enzyme immunoassay of intraocular fluid. Descemet membrane/endothelium çomplexes (1a, 1b groups and control group (5 of 12 preserved human corneas) were stained with hematoxylin/eosin. Descemet membrane/endothelium çomplexes (2a, 2b groups and control group (7 of 12 preserved human corneas) were stained with ZO-1, α-SMА antibodies, nuclei were counterstained (Hoechst 33342).
RESULTS: TGF-β1 level was elevated in 1a group (p <0.05). In 1a group Descemet membrane was thickened by guttae. Descemet membrane/endothelium çomplexes of 2a, 2b groups presented enlarged endothelial cells with lower levels of ZO-1 expression. There was an increase in nuclear areas in 2a, 2b groups compared to controls (p <0.05). Nuclear aspect ratio was lower in 2a, 2b groups compared to the controls (p <0.05). In 2a group endothelial cells showed high level of α-SMА expression.
CONCLUSION: Fuchs endothelial dystrophy and pseudophakic bullous keratopathy are conditions of different structural changes in Descemet membrane/endothelium çomplexes. TGF-β1 may play a pivotal role in guttae formation in Fuchs endothelial dystrophy.
corneal endothelium / Descemet membrane / Fuchs endothelial dystrophy / bullous keratopathy / TGF-β1 / ZO-1
| [1] |
Meek KM, Knupp C. Corneal structure and transparency. Prog Retin Eye Res. 2015;49:1–16. doi: 10.1016/j.preteyeres.2015.07.001 |
| [2] |
Meek K.M., Knupp C. Corneal structure and transparency // Prog Retin Eye Res. 2015. Vol. 49. P. 1–16. doi: 10.1016/j.preteyeres.2015.07.001 |
| [3] |
Joyce NC. Cell cycle status in human corneal endothelium. Exp Eye Res. 2005;81(6):629–638. doi: 10.1016/j.exer.2005.06.012 |
| [4] |
Joyce N.C. Cell cycle status in human corneal endothelium // Exp Eye Res. 2005. Vol. 81, N 6. P. 629–638. doi: 10.1016/j.exer.2005.06.012 |
| [5] |
Edelhauser HF. The balance between corneal transparency and edema: the proctor lecture. Invest Ophthalmol Vis Sci. 2006;47(5):1754–1767. doi: 10.1167/iovs.05-1139 |
| [6] |
Edelhauser H.F. The balance between corneal transparency and edema: the Proctor lecture // Invest Ophthalmol Vis Sci. 2006. Vol. 47, N 5. P. 1754–1767. doi: 10.1167/iovs.05-1139 |
| [7] |
Pricopie S, Istrate S, Voinea L, et al. Pseudophakic bullous keratopathy. Rom J Ophthalmol. 2017;61(2):90–94. doi: 10.22336/rjo.2017.17 |
| [8] |
Pricopie S., Istrate S., Voinea L., et al. Pseudophakic bullous keratopathy // Rom J Ophthalmol. 2017. Vol. 61, N 2. P. 90–94. doi: 10.22336/rjo.2017.17 |
| [9] |
Price MO, Mehta JS, Jurkunas UV, Price FW Jr. Corneal endothelial dysfunction: Evolving understanding and treatment options. Prog Retin Eye Res. 2021;82:100904. doi: 10.1016/j.preteyeres.2020.100904 |
| [10] |
Price M.O., Mehta J.S., Jurkunas U.V., Price F.W. Jr. Corneal endothelial dysfunction: evolving understanding and treatment options // Prog Retin Eye Res. 2021. Vol. 82. P. 100904. doi: 10.1016/j.preteyeres.2020.100904 |
| [11] |
Matthaei M, Hribek A, Clahsen T, et al. Fuchs endothelial corneal dystrophy: clinical, genetic, pathophysiologic, and therapeutic aspects. Annu Rev Vis Sci. 2019;5:151–175. doi: 10.1146/annurev-vision-091718-014852 |
| [12] |
Matthaei M., Hribek A., Clahsen T., et al. Fuchs endothelial corneal dystrophy: clinical, genetic, pathophysiologic, and therapeutic aspects // Annu Rev Vis Sci. 2019. Vol. 5. P. 151–175. doi: 10.1146/annurev-vision-091718-014852 |
| [13] |
Okumura N, Hashimoto K, Kitahara M, et al. Activation of TGF-β signaling induces cell death via the unfolded protein response in Fuchs endothelial corneal dystrophy. Sci Rep. 2017;7(1):6801. doi: 10.1038/s41598-017-06924-3 |
| [14] |
Okumura N., Hashimoto K., Kitahara M., et al. Activation of TGF-β signaling induces cell death via the unfolded protein response in Fuchs endothelial corneal dystrophy // Sci Rep. 2017. Vol. 7, N 1. P. 6801. doi: 10.1038/s41598-017-06924-3 |
| [15] |
Katikireddy KR, White TL, Miyajima T, et al. NQO1 downregulation potentiates menadione-induced endothelial-mesenchymal transition during rosette formation in Fuchs endothelial corneal dystrophy. Free Radic Biol Med. 2018;116:19–30. doi: 10.1016/j.freeradbiomed.2017.12.036 |
| [16] |
Katikireddy K.R., White T.L., Miyajima T., et al. NQO1 downregulation potentiates menadione-induced endothelial-mesenchymal transition during rosette formation in Fuchs endothelial corneal dystrophy // Free Radic Biol Med. 2018. Vol. 116. P. 19–30. doi: 10.1016/j.freeradbiomed.2017.12.036 |
| [17] |
Okumura N, Minamiyama R, Ho L, et al. Involvement of ZEB1 and Snail1 in excessive production of extracellular matrix in Fuchs endothelial corneal dystrophy. Lab Invest. 2015;95:1291–1304. doi: 10.1038/labinvest.2015.111 |
| [18] |
Okumura N., Minamiyama R., Ho L., et al. Involvement of ZEB1 and Snail1 in excessive production of extracellular matrix in Fuchs endothelial corneal dystrophy // Lab Invest. 2015. Vol. 95. P. 1291–1304. doi: 10.1038/labinvest.2015.111 |
| [19] |
Brockmann T, Brockmann C, Maier AB, et al. Primary Descemet’s membrane endothelial keratoplasty for Fuchs endothelial dystrophy versus bullous keratopathy: histopathology and clinical results. Curr Eye Res. 2018;43(10):1221–1227. doi: 10.1080/02713683.2018.1490773 |
| [20] |
Brockmann T., Brockmann C., Maier A.B., et al. Primary Descemet’s membrane endothelial keratoplasty for Fuchs endothelial dystrophy versus bullous keratopathy: histopathology and clinical results // Curr Eye Res. 2018. Vol. 43, N 10. P. 1221–1227. doi: 10.1080/02713683.2018.1490773 |
| [21] |
Bourne WM, Johnson DH, Campbell RJ. The ultrastructure of Descemet’s membrane. III. Fuchs’ dystrophy. Arch Ophthalmol. 1982;100(12):1952–1955. doi: 10.1001/archopht.1982.01030040932013 |
| [22] |
Bourne W.M., Johnson D.H., Campbell R.J. The ultrastructure of Descemet’s membrane. III. Fuchs’ dystrophy // Arch Ophthalmol. 1982. Vol. 100, N 12. P. 1952–1955. doi: 10.1001/archopht.1982.01030040932013 |
| [23] |
de Oliveira RC, Wilson SE. Descemet’s membrane development, structure, function and regeneration. Exp Eye Res. 2020;197:108090. doi: 10.1016/j.exer.2020.108090 |
| [24] |
de Oliveira R.C., Wilson S.E. Descemet’s membrane development, structure, function and regeneration // Exp Eye Res. 2020. Vol. 197. P. 108090. doi: 10.1016/j.exer.2020.108090 |
| [25] |
Halfter W, Moes S, Halfter K, et al. The human Descemet’s membrane and lens capsule: protein composition and biomechanical properties. Exp Eye Res. 2020;201:108326. doi: 10.1016/j.exer.2020.108326 |
| [26] |
Halfter W., Moes S., Halfter K., et al. The human Descemet’s membrane and lens capsule: protein composition and biomechanical properties // Exp Eye Res. 2020. Vol. 201. P. 108326. doi: 10.1016/j.exer.2020.108326 |
| [27] |
Murphy C, Alvarado J, Juster R. Prenatal and postnatal growth of the human Descemet’s membrane. Invest Ophthalmol Vis Sci. 1984;25(12):1402–1415. |
| [28] |
Murphy C., Alvarado J., Juster R. Prenatal and postnatal growth of the human Descemet’s membrane // Invest Ophthalmol Vis Sci. 1984. Vol. 25, N 12. P. 1402–1415. |
| [29] |
Xia D, Zhang S, Nielsen E, et al. The ultrastructures and mechanical properties of the Descement’s membrane in Fuchs endothelial corneal dystrophy. Sci Rep. 2016;6:23096. doi: 10.1038/srep23096 |
| [30] |
Xia D., Zhang S., Nielsen E., et al. The ultrastructures and mechanical properties of the Descement’s membrane in Fuchs endothelial corneal dystrophy // Sci Rep. 2016. Vol. 6. P. 23096. doi: 10.1038/srep23096 |
| [31] |
Johnson DH, Bourne WM, Campbell RJ. The ultrastructure of Descemet’s membrane. I. Changes with age in normal corneas. Arch Ophthalmol. 1982;100(12):1942–1947. doi: 10.1001/archopht.1982.01030040922011 |
| [32] |
Johnson D.H., Bourne W.M., Campbell R.J. The ultrastructure of Descemet’s membrane. I. Changes with age in normal corneas // Arch Ophthalmol. 1982. Vol. 100, N 12. P. 1942–1947. doi: 10.1001/archopht.1982.01030040922011 |
| [33] |
Iliff BW, Riazuddin SA, Gottsch JD. The genetics of Fuchs’ corneal dystrophy. Expert Rev Ophthalmol. 2012;7(4):363–375. doi: 10.1586/eop.12.39. PMID: 23585771 |
| [34] |
Iliff B.W., Riazuddin S.A., Gottsch J.D. The genetics of Fuchs’ corneal dystrophy // Expert Rev Ophthalmol. 2012. Vol. 7, N 4. P. 363–375. doi: 10.1586/eop.12.39. PMID: 23585771 |
| [35] |
Gupta R, Kumawat BL, Paliwal P, et al. Association of ZEB1 and TCF4 rs613872 changes with late onset Fuchs endothelial corneal dystrophy in patients from northern India. Mol Vis. 2015;21:1252–1260. |
| [36] |
Gupta R., Kumawat B.L., Paliwal P., et al. Association of ZEB1 and TCF4 rs613872 changes with late onset Fuchs endothelial corneal dystrophy in patients from northern India // Mol Vis. 2015. Vol. 21. P. 1252–1260. |
| [37] |
Jurkunas UV, Bitar M, Rawe I. Co-localization of increased Transforming growth factor Beta induced protein (TGFBIp) and Clusterin expression in guttae of Fuchs endothelial corneal dystrophy patients. Invest Ophthalmol Vis Sci. 2009;50(3):1129–1136. doi: 10.1167/iovs.08-2525 |
| [38] |
Jurkunas U.V., Bitar M., Rawe I. Co-localization of increased Transforming growth factor Beta induced protein (TGFBIp) and Clusterin expression in guttae of Fuchs endothelial corneal dystrophy // Invest Ophthalmol Vis Sci. 2009. Vol. 50, N 3. P. 1129–1136. doi: 10.1167/iovs.08-2525 |
| [39] |
Kuot A, Hewitt AW, Griggs K, et al. Association of TCF4 and CLU polymorphisms with Fuchs’ endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process. Eur J Hum Genet. 2012;20(6):632–638. doi: 10.1038/ejhg.2011.248 |
| [40] |
Kuot A., Hewitt A.W., Griggs K., et al. Association of TCF4 and CLU polymorphisms with Fuchs’ endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process // Eur J Hum Genet. 2012. Vol. 20, N 6. P. 632–638. doi: 10.1038/ejhg.2011.248 |
| [41] |
Weller JM, Zenkel M, Schlotzer-Schrehardt U, et al. Extracellular matrix alterations in late-onset Fuchs’ corneal dystrophy. Invest Ophthalmol Vis Sci. 2014;55(6):3700–3708. doi: 10.1167/iovs.14-14154 |
| [42] |
Weller J.M., Zenkel M., Schlotzer-Schrehardt U., et al. Extracellular matrix alterations in late-onset Fuchs’ corneal dystrophy // Invest Ophthalmol Vis Sci. 2014. Vol. 55, N 6. P. 3700–3708. doi: 10.1167/iovs.14-14154 |
| [43] |
Matthaei M, Gillessen J, Muether PS, et al. Epithelial-mesenchymal transition (EMT)-related cytokines in the aqueous humor of phakic and pseudophakic Fuchs’ Dystrophy eyes. Invest Ophthalmol Vis Sci. 2015;56(4):2749–2754. doi: 10.1167/iovs.15-16395 |
| [44] |
Matthaei M., Gillessen J., Muether P.S., et al. Epithelial-mesenchymal transition (EMT)-related cytokines in the aqueous humor of phakic and pseudophakic Fuchs’ Dystrophy eyes // Invest Ophthalmol Vis Sci. 2015. Vol. 56, N 4. P. 2749–2754. doi: 10.1167/iovs.15-16395 |
| [45] |
Ong TS, Jurkunas U. Imaging the corneal endothelium in Fuchs corneal endothelial dystrophy. Semin Ophthalmol. 2019;34(4):340–346. doi: 10.1080/08820538.2019.1632355 |
| [46] |
Ong T.S, Jurkunas U. Imaging the corneal endothelium in Fuchs corneal endothelial dystrophy // Semin Ophthalmol. 2019. Vol. 34, N 4. P. 340–346. doi: 10.1080/08820538.2019.1632355 |
Eco-Vector
/
| 〈 |
|
〉 |