Skip to main content
Log in

Corneal Endothelial Cell Volume Regulation Disorders in Keratoconus

  • Published:
Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

The study of the permeability to water and urea of plasma membranes of endothelial cells of the normal cornea and cornea with a pronounced form of keratoconus was carried out. Human corneal endothelial cells were obtained from surgical material. Determination of osmotic water permeability (Pf) of normal and keratoconus endothelial cells did not reveal significant differences in the value of this parameter in both groups, where cells had a similar osmotic water permeability (control Pf = 0.53 ± 0.045 cm/s; keratoconus Pf = 0.63 ± 0.041 cm/s) (n = 25; p ≥ 0.05). The urea permeability coefficients (Pu) in both groups also had no statistically significant differences (control Pu = 0.049 ± 0.003 cm/s; keratoconus Pu = 0.056 ± 0.003 cm/s) (n = 25; p ≥ 0.05). Analysis of cell volume dynamics based on exponential approximation showed that corneal endothelial cells with keratoconus reduced their volume in a hypertonic medium to a greater extent compared to cells of a healthy cornea. An increase in cell volume as a result of isotonic urea inflow in a hypertonic medium also occurred to significantly higher values compared to normal cells. The conclusion was made about significant changes in the mechanism of regulation of the volume of corneal endothelial cells in keratoconus.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.
Fig. 4.
Fig. 5.

REFERENCES

  1. Santodomingo-Rubido J., Carracedo G., Suzaki A., Villa-Collar C., Vincen S.J., Wolffsohn J.S. 2022. Keratoconus: An updated review. Cont. Lens Anterior Eye. 45 (3), 101559.

    Article  PubMed  Google Scholar 

  2. Scroggs M.W., Proia A.D. 1992. Histopathological variation in keratoconus. Cornea 11 (6), 553–559.

    Article  CAS  PubMed  Google Scholar 

  3. Bitirgen G., Ozkagnici A., Bozkurt B., Malik R.A. 2015. In vivo corneal confocal microscopic analysis in patients with keratoconus. Int. J. Ophthalmol. 8, 534–539.

    PubMed  PubMed Central  Google Scholar 

  4. Khaled M.L., Helwa I., Drewry M., Seremwe M., Estes A., Liu Y. 2017. Molecular and histopathological changes associated with keratoconus. Biomed. Res. Int. 2017, 7803029.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Rabinowitz Y.S. 1998. Keratoconus. Surv. Ophthalmol. 42, 297–319.

    Article  CAS  PubMed  Google Scholar 

  6. Ghosh S., Mutalib H.A., Kaur S., Ghoshal R., Retnasabapathy S. 2017. Corneal cell morphology in keratoconus: A confocal microscopic observation. Malays J. Med. Sci. 24 (2), 44–54.

    PubMed  PubMed Central  Google Scholar 

  7. Weed K.H., MacEwen C.J., Cox A., McGhee C.N.J. 2007. Quantitative analysis of corneal microstructure in keratoconus utilising in vivo confocal microscopy. Eye. 21 (5), 614–623.

    Article  CAS  PubMed  Google Scholar 

  8. Efron N., Hollingsworth J.G. 2008. New perspectives on keratoconus as revealed by corneal confocal microscopy. Clin. Exp. Optom. 91 (1), 34–55.

    Article  PubMed  Google Scholar 

  9. El-Agha M.S.H., Sayed Y.M.E., Harhara R.M., Essam H.M. 2014. Correlation of corneal endothelial changes with different stages of keratoconus. Cornea. 33 (7), 707–711.

    Article  PubMed  Google Scholar 

  10. Marianne O.P., Jodhbir S.M., Ula V.J., Francis W.P. 2021 Corneal endothelial dysfunction: Evolving understanding and treatment options. Progr. Retinal Eye Res. 82, 100904.

    Article  Google Scholar 

  11. Fernandes B.F., Logan P., Zajdenweber M.E., Santos L.N., Cheema D.P., Burnier M.N. 2008. Histopathological study of 49 cases of keratoconus. Pathology. 40 (6), 623–626.

    Article  PubMed  Google Scholar 

  12. Mocan M.C., Yilmaz P.T., Irkec M., Orhan M. 2008. In vivo confocal microscopy for the evaluation of corneal microstructure in keratoconus. Curr. Eye Res. 33 (11), 933–939.

    Article  PubMed  Google Scholar 

  13. Loukovitis E., Kozeis N., Gatzioufas Z., Kozei A., Tsotridou E., Stoila M., Koronis S., Sfakianakis K., Tranos P., Balidis M., Zachariadis Z., Mikropoulos D.G., Anogeianakis G., Katsanos A., Konstas A.G. 2019. The proteins of keratoconus: A literature review exploring their contribution to the pathophysiology of the disease. Adv. Ther. 36 (9), 2205–2222.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yam G.H.F., Fuest M., Zhou L., Liu Y.C., Deng L., Chan A.S. Ong H.S., Khor W.B., Ang M., Mehta J.S. 2019. Differential epithelial and stromal protein profiles in cone and non-cone regions of keratoconus corneas. Sci. Rep. 9 (1), 2965

    Article  PubMed  PubMed Central  Google Scholar 

  15. Srivastava O.P. Chandrasekaran D., Pfister R.R. 2006. Molecular changes in selected epithelial proteins in human keratoconus corneas compared to normal corneas. Mol. Vis. 12, 1615–1625.

    CAS  PubMed  Google Scholar 

  16. Fan Gaskin J.C., Patel D.V., McGhee C.N.J. 2014. Acute corneal hydrops in keratoconus – new perspectives. Am. J. Ophthalmol. 157 (5), 921–928.

    Article  PubMed  Google Scholar 

  17. Yahia Chérif H., Gueudry J., Afriat M., Delcampe A., Attal P., Gross H., Muraine M. 2015. Efficacy and safety of pre-Descemet’s membrane sutures for the management of acute corneal hydrops in keratoconus. Br. J. Ophthalmol. 99 (6), 773–777.

    Article  PubMed  Google Scholar 

  18. Mathew J.H., Goosey J.D., Söderberg P.G., Bergmanson J.P.G. 2015. Lamellar changes in the keratoconic cornea. Acta Ophthalmol. 93 (8), 767–773.

    Article  CAS  PubMed  Google Scholar 

  19. Bonanno J.A. 2012. Molecular mechanisms underlying the corneal endothelial pump. Exp. Eye Res. 95 (1), 2–7.

    Article  CAS  PubMed  Google Scholar 

  20. Lang F., Busch G.L., Ritter M., Volkl H., Waldegger S., Gulbins E., Haussinger D. 1998. Functional significance of cell volume regulatory mechanisms. Physiol. Rev. 78, 247–306.

    Article  CAS  PubMed  Google Scholar 

  21. O’Neill W.C. 1999. Physiological significance of volume-regulatory transporters. Am. J. Physiol. Cell Physiol. 276, C995–C1011.

    Article  Google Scholar 

  22. Strange K. 2004. Cellular volume homeostasis. Adv. Physiol. Educ. 28 (1–4), 155–159.

    Article  PubMed  Google Scholar 

  23. Gulotta M., Qiu L., Desamero R., Rösgen J., Bolen D.W., Callender R. 2007. Effects of cell volume regulating osmolytes on glycerol 3-phosphate binding to triosephosphate isomerase. Biochemistry. 46 (35), 10055–10062.

    Article  CAS  PubMed  Google Scholar 

  24. Alvarez B.V., Piché M., Aizouki C., Rahman F., Derry J.M.J., Brunette I., Casey J.R. 2021. Altered gene expression in slc4a11–/– mouse cornea highlights SLC4A11 roles. Sci. Rep. 11 (1), 20885.https://doi.org/10.1038/s41598-021-98921-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Nakayama Y., Naruse M., Karakashian A., Peng T., Sands J.M., Bagnasco S.M. 2001. Cloning of the rat Slc14a2 gene and genomic organization of the UT-A urea transporter. Biochim. Biophys. Acta. 1518 (1–2), 19–26.

  26. Bagnasco S.M., Peng T., Janech M.G., Karakashian A., Sands J.M. 2001. Cloning and characterization of the human urea transporter UT-A1 and mapping of the human Slc14a2 gene. Am. J. Physiol. Renal Physiol. 281 (3), F400-6.

    Article  CAS  PubMed  Google Scholar 

  27. Solenov E., Watanabe H., Manley G.T., Verkman A.S. 2004. Sevenfold-reduced osmotic water permeability in primary astrocyte cultures from AQP-4-deficient mice, measured by a fluorescence quenching method. Am. J. Physiol. Cell Physiol. 286 (2), 426–432.

    Article  Google Scholar 

  28. Baturina G.S., Katkova L.E., Kolosova N.G., Solenov E.I. 2017. Changes in water transport by corneal endothelial cells in rats during aging. Uspekhi Gerontologii (Advances in Gerontology) (Rus). 30 (5), 659–664.

    CAS  PubMed  Google Scholar 

  29. Zarogiannis S.G., Ilyaskin A.V., Baturina G.S., Katkova L.E., Medvedev D.A., Karpov D.I., Ershov A.P., Solenov E.I. 2013. Regulatory volume decrease of rat kidney principal cells after successive hypo-osmotic shocks. Math. Biosci. 244 (2), 176–187.

    Article  PubMed  Google Scholar 

  30. Solenov E.I., Baturina G.S., Ilyaskin A.V., Katkova L.Y., Ivanova L.N. 2011. Cell volume regulation of rat kidney collecting duct epithelial cells in hypotonic medium. Dokl. Biol. Sci. 436, 13–55.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

The work was carried out with the support of budget project no. FWNR-2022-0019.

Author information

Authors and Affiliations

Authors

Contributions

The idea of the study and planning of the experiments (E.I. Solenov and I.A. Iskakov), collection of data (G.S. Baturina, L.E. Katkova, I.M. Kuzeina, and E.I. Solenov), data processing and manuscript writing (G.S. Baturina, L.E. Katkova, I.M. Kuzeina, and E.I. Solenov), discussion and editing of the manuscript (G.S. Baturina, L.E. Katkova, E.I. Solenov, I.G. Palchikova, and I.A. Iskakov).

Corresponding author

Correspondence to E. I. Solenov.

Ethics declarations

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The study was conducted in accordance with the principles of the Helsinki Declaration of the World Medical Association “Ethical Principles of Conducting Scientific medical research with human participation”, Federal Law of the Russian Federation No. 323 FZ dated November 21, 2011 “On the Basics of Protecting the Health of Citizens in the Russian Federation”, as well as the requirements of Federal Law No. 152-FZ dated July 27, 2006 (ed. July 21, 2014) “On personal data” (with amendments and additions, effective from September 1, 2015). The sampling of the material was carried out by employees of the Novosibirsk branch of the S.N. Fedorov NMRC “MNTK “Eye microsurgery” Ministry of Health of Russia. Permission was received from the Bioethical Committee of the Novosibirsk branch of the S.N. Fedorov NMRC “MNTK “Eye microsurgery” to conduct the study. All patients gave written informed consent to the study of biological material and the use of the data obtained for scientific purposes.

CONFLICT OF INTEREST

The authors of this work declare that they have no conflicts of interest.

Additional information

Translated by E. Puchkov

Publisher’s Note.

Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kuseina, I.M., Katkova, L.E., Baturina, G.S. et al. Corneal Endothelial Cell Volume Regulation Disorders in Keratoconus. Biochem. Moscow Suppl. Ser. A 18, 44–50 (2024). https://doi.org/10.1134/S1990747824700065

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1990747824700065

Keywords:

Navigation