Review
BibTex RIS Cite

Value of Aquaporins in the Eyes

Year 2025, Volume: 7 Issue: 2, 280 - 288, 23.06.2025
https://doi.org/10.52827/hititmedj.1532970

Abstract

Aquaporins (AQPs) are small integrated membrane proteins that enable water conduction across the plasma membranes of cells as a result of osmotic gradients. AQPs have been indicated to be involved in the molecular adjustment of many biological functions such as osmolarity, cell movement, junctional adhesion, management of surface protein expression, transepithelial water transport, energy metabolism, cellular proliferation, neuroexcitation, extracellular matrix stress regulation, cellular water adjustment. In addition to regulating aqueous humor balance, it also facilitates the removal of many residuals products of the cornea, lens, ciliary body and retina while preserving clarity in the optic compartments. Studies have ascertained the value of mammalian AQPs in both pathophysiological and physiological conditions. This suggests that pharmacological modulation of aquaporin expression and tasks may provide a novel therapy for the amelioration of various vision-related pathologies that may involve water and small solute transport. This review clarifies the physiological roles of AQPs in the eye and their involvement in pathological conditions in light of previous studies and highlights the development of selective pharmacological target strategies that may be beneficial for the treatment of related conditions, mobilization.

References

  • Bhend ME, Kempuraj D, Sinha NR, Gupta S, Mohan RR. Role of aquaporins in corneal healing post chemical injury. Experimental Eye Research 2023;228:109390.
  • Ahmed T, Ghafoor S. Aquaporins; systemic, functional and therapeutic correlations in health and disease. JPMA The Journal of the Pakistan Medical Association 2021;71:1228-1233.
  • Soyfoo MS, Chivasso C, Perret J, Delporte C. Involvement of aquaporins in the pathogenesis, diagnosis and treatment of Sjögren’s syndrome. International journal of molecular sciences 2018;19:3392.
  • Ishibashi K, Morishita Y, Tanaka Y. The evolutionary aspects of aquaporin family, Aquaporins 2017;35-50.
  • Delporte C, Bryla A, Perret J. Aquaporins in salivary glands: from basic research to clinical applications. International journal of molecular sciences 2016;17:166.
  • Sanal F. Akuaforinler. Türk Bilimsel Derlemeler Dergisi 2008;1:33-45.
  • Frigeri A, Nicchia GP, Svelto M. Aquaporins as targets for drug discovery. Current pharmaceutical design 2007;13:2421-2427.
  • Schey KL, Wang Z, Wenke JL, Qi Y. Aquaporins in the eye: expression, function, and roles in ocular disease. Biochimica et Biophysica Acta (BBA)-General Subjects 2014;1840:1513-1523.
  • Verkman AS, Anderson MO, Papadopoulos MC. Aquaporins: important but elusive drug targets. Nature reviews Drug discovery 2014;13:259-277.
  • Schey KL, Petrova RS, Gletten RB, Donaldson PJ. The role of aquaporins in ocular lens homeostasis. International journal of molecular sciences 2017;18:2693.
  • Li Z, Quan Y, Gu S, Jiang JX. Beyond the channels: adhesion functions of aquaporin 0 and connexin 50 in lens development. Frontiers in Cell and Developmental Biology 2022;10:866980.
  • Sun W, Xu, J, Gu Y, Du C. The relationship between major intrinsic protein genes and cataract. International Ophthalmology 2021;41:375-387.
  • Chepelinsky AB. Structural Function of MIP/Aquaporin 0 in the Eye Lens; Genetic Defects Lead to Congenital Inherited Cataracts. In: Beitz, E. (eds) Aquaporins. Handbook of Experimental Pharmacology; 2009. p. 265-266.
  • Németh-Cahalan KL, Kalman K, Hall JE. Molecular basis of pH and Ca2+ regulation of aquaporin water permeability. The Journal of general physiology 2004;123:573-580.
  • Mulders SM, Preston GM, Deen PM, Guggino WB, van Os CH, Agre P. Water channel properties of major intrinsic protein of lens. J Biol Chem 1995;270:9010–9016.
  • Nemeth-Cahalan KL, Hall JE. pH and calcium regulate the water permeability of aquaporin0. J Biol Chem 2000;275:6777–6782.
  • Varadaraj K, Kumari S, Shiels A, Mathias RT. Regulation of aquaporin water permeability in the lens. Invest Ophthalmol Vis Sci 2005;46:1393–1402.
  • D’Agostino C, Parisis D, Chivasso C, Hajiabbas M, Soyfoo MS, Delporte C. Aquaporin-5 Dynamic Regulation. International journal of molecular sciences 2023;24:1889.
  • Rodrigues C, Mósca AF, Martins AP et al. Rat aquaporin-5 is pH-gated induced by phosphorylation and is implicated in oxidative stress. International Journal of Molecular Sciences 2016;17:2090.
  • Yasui M, Hazama A, Kwon TH, Nielsen S, Guggino WB, Agre P. Rapid gating and anion permeability of an intracellular aquaporin Nature. 1999;402:184-187.
  • Nemeth-Cahalan KL, Kalman K, Froger A, Hall JE. Zinc modulation of water permeability reveals that aquaporin 0 functions as a cooperative tetramer. J Gen Physiol 2007;130:457–464.
  • Chandy G, Zampighi GA, Kreman M, Hall JE. Comparison of the water transporting properties of MIP and AQP1. The Journal of membrane biology 1997;159:29-39.
  • Hamann S, Zeuthen T, La Cour M, et al. Aquaporins in complex tissues: distribution of aquaporins 1-5 in human and rat eye. Am J Physiol 1998;274:1332-1345.
  • Kenney MC, Atilano SR, Zorapapel N, Holguin B, Gaster RN, Ljubimov AV. Altered expression of aquaporins in bullous keratopathy and Fuchs’ dystrophy corneas. J. Histochem. Cytochem 2004;52:1341–1350.
  • Funaki H, Yamamoto T, Koyama Y et al. Localization and expression of AQP5 in cornea, serous salivary glands, and pulmonary epithelial cells. Am. J. Physiol 1998;275:1151–1157.
  • Tran TL, Bek T, la Cour M et al. Altered aquaporin expression in glaucoma eyes. APMIS 2014;122:772–780.
  • Tran TL, Bek T, Holm L, et al. Aquaporins 6-12 in the human eye. Acta Ophthalmol 2013;91:557–563.
  • Kumari SS, Varadaraj K. Aquaporin 5 knockout mouse lens develops hyperglycemic cataract. Biochemical and biophysical research communications 2013;441:333-338.
  • Agre P, King LS, Yasui M et al. Aquaporin water channels– from atomic structure to clinical medicine. The Journal of physiology 2002;542:3-16.
  • Varadaraj K, Kumari SS. Molecular mechanism of Aquaporin 0-induced fiber cell to fiber cell adhesion in the eye lens. Biochemical and biophysical research communications 2018;506:284-289.
  • Costello MJ, McIntosh TJ, Robertson, JD. Distribution of gap junctions and square array junctions in the mammalian lens. Investigative ophthalmology & visual science 1989;30:975-989.
  • Freites JA, Németh-Cahalan KL, Hall JE, Tobias DJ. Cooperativity and allostery in aquaporin 0 regulation by Ca2+. Biochimica et Biophysica Acta (BBA)-Biomembranes 2019;1861:988-996.
  • Zhang, D, Vetrivel, L, Verkman, AS. Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production. The Journal of general physiology 2022;119:561-569.
  • Delporte C. Aquaporins and gland secretion. Aquaporins 2017;969:63-79.
  • Delporte C, Soyfoo M. Aquaporins: Unexpected actors in autoimmune diseases. Autoimmunity Reviews 2022;21(8):103131.
  • Haydinger CD, Ferreira LB, Williams KA, Smith JR. Mechanisms of macular edema. Front Med (Lausanne) 2023;10:1128811.
  • Hashemi H, Pakzad R, Yekta A et al. Global and regional prevalence of age-related cataract: a comprehensive systematic review and meta-analysis. Eye 2020;34:1357-1370.
  • Ishida H, Shibata T, Nakamura Y et al. Identification of Differential Gene Expression Pattern in Lens Epithelial Cells Derived from Cataractous and Noncataractous Lenses of Shumiya Cataract Rat. BioMed research international 2020;2:7319590.
  • Barandika O, Ezquerra-Inchausti M, Anasagasti A et al. Increased aquaporin 1 and 5 membrane expression in the lens epithelium of cataract patients. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2016;1862:2015-2021.
  • Hayashi R, Hayashi S, Fukuda K, Sakai M, Machida S. Immunolocation of aquaporin 8 in human cataractous lenticular epithelial cells. Biomedicine hub 2018;2:1-5.
  • Huang OS, Seet LF, Ho HW et al. Altered iris aquaporin expression and aqueous humor osmolality in glaucoma. Investigative Ophthalmology & Visual Science 2021;62:34-34.
  • Tran, TL, Hamann S, Heegaard S. Aquaporins in the eye. Aquaporins 2017;193-198.
  • Lai Z, Yin H, Cabrera-Pérez J et al. Aquaporin gene therapy corrects Sjögren’s syndrome phenotype in mice. Proceedings of the National Academy of Sciences 2016;113:5694-5699.
  • Papadopoulos MC, Verkman A. Aquaporin 4 and neuromyelitis optica. The Lancet Neurology 2012;11:535-544.

Akuaporinlerin Gözdeki Değeri

Year 2025, Volume: 7 Issue: 2, 280 - 288, 23.06.2025
https://doi.org/10.52827/hititmedj.1532970

Abstract

Akuaporinler (AQP’ler), ozmotik gradyanlara yanıt olarak hücrelerin plazma zarları boyunca su taşınmasını kolaylaştıran küçük, entegre zar proteinlerinin bir ailesidir. AQP’lerin; ozmolarite, hücre göçü, bağlantı adezyonu, yüzey proteini üretiminin düzenlenmesi, transepitelyal su transportu, hücresel proliferasyon, nöroeksitasyon, hücre dışı matris stres düzenlemesi, enerji metabolizması ve hücresel su düzenlemesi gibi birçok biyolojik fonksiyonun moleküler düzeyde düzenlemesinde yer aldığı belirtilmiştir. Göz yapılarının şeffaflığını korumasının yanında aköz hümör dengesinin düzenlenmesi, kornea, siliyer cisim, lens ve retina gibi dokuların metabolik ürünlerinin temizlenmesini de sağlamaktadır. Yapılan çalışmalar, memeli AQP’lerin hem fizyolojik hem de patofizyolojik ortamlardaki önemini ortaya çıkarmıştır. Bu, akuaporin ekspresyonunun ve aktivitesinin, farmakolojik modülasyonunun, su ve çözünebilen küçük maddelerin taşınmasının da dahil olabileceği çeşitli görme ile ilgili bozuklukların tedavisi için yeni araçlar sağlayabileceğini göstermektedir. Bu derleme, AQP’lerin göz organındaki fizyolojik rolünü ve patolojik durumlara katılımını yapılan çalışmalar ışığında açıklamakla birlikte ilgili durumların tedavileri için yararlı olabilecek hedefe yönelik farmakolojik stratejilerin geliştirilmesini vurgulamaktadır.

References

  • Bhend ME, Kempuraj D, Sinha NR, Gupta S, Mohan RR. Role of aquaporins in corneal healing post chemical injury. Experimental Eye Research 2023;228:109390.
  • Ahmed T, Ghafoor S. Aquaporins; systemic, functional and therapeutic correlations in health and disease. JPMA The Journal of the Pakistan Medical Association 2021;71:1228-1233.
  • Soyfoo MS, Chivasso C, Perret J, Delporte C. Involvement of aquaporins in the pathogenesis, diagnosis and treatment of Sjögren’s syndrome. International journal of molecular sciences 2018;19:3392.
  • Ishibashi K, Morishita Y, Tanaka Y. The evolutionary aspects of aquaporin family, Aquaporins 2017;35-50.
  • Delporte C, Bryla A, Perret J. Aquaporins in salivary glands: from basic research to clinical applications. International journal of molecular sciences 2016;17:166.
  • Sanal F. Akuaforinler. Türk Bilimsel Derlemeler Dergisi 2008;1:33-45.
  • Frigeri A, Nicchia GP, Svelto M. Aquaporins as targets for drug discovery. Current pharmaceutical design 2007;13:2421-2427.
  • Schey KL, Wang Z, Wenke JL, Qi Y. Aquaporins in the eye: expression, function, and roles in ocular disease. Biochimica et Biophysica Acta (BBA)-General Subjects 2014;1840:1513-1523.
  • Verkman AS, Anderson MO, Papadopoulos MC. Aquaporins: important but elusive drug targets. Nature reviews Drug discovery 2014;13:259-277.
  • Schey KL, Petrova RS, Gletten RB, Donaldson PJ. The role of aquaporins in ocular lens homeostasis. International journal of molecular sciences 2017;18:2693.
  • Li Z, Quan Y, Gu S, Jiang JX. Beyond the channels: adhesion functions of aquaporin 0 and connexin 50 in lens development. Frontiers in Cell and Developmental Biology 2022;10:866980.
  • Sun W, Xu, J, Gu Y, Du C. The relationship between major intrinsic protein genes and cataract. International Ophthalmology 2021;41:375-387.
  • Chepelinsky AB. Structural Function of MIP/Aquaporin 0 in the Eye Lens; Genetic Defects Lead to Congenital Inherited Cataracts. In: Beitz, E. (eds) Aquaporins. Handbook of Experimental Pharmacology; 2009. p. 265-266.
  • Németh-Cahalan KL, Kalman K, Hall JE. Molecular basis of pH and Ca2+ regulation of aquaporin water permeability. The Journal of general physiology 2004;123:573-580.
  • Mulders SM, Preston GM, Deen PM, Guggino WB, van Os CH, Agre P. Water channel properties of major intrinsic protein of lens. J Biol Chem 1995;270:9010–9016.
  • Nemeth-Cahalan KL, Hall JE. pH and calcium regulate the water permeability of aquaporin0. J Biol Chem 2000;275:6777–6782.
  • Varadaraj K, Kumari S, Shiels A, Mathias RT. Regulation of aquaporin water permeability in the lens. Invest Ophthalmol Vis Sci 2005;46:1393–1402.
  • D’Agostino C, Parisis D, Chivasso C, Hajiabbas M, Soyfoo MS, Delporte C. Aquaporin-5 Dynamic Regulation. International journal of molecular sciences 2023;24:1889.
  • Rodrigues C, Mósca AF, Martins AP et al. Rat aquaporin-5 is pH-gated induced by phosphorylation and is implicated in oxidative stress. International Journal of Molecular Sciences 2016;17:2090.
  • Yasui M, Hazama A, Kwon TH, Nielsen S, Guggino WB, Agre P. Rapid gating and anion permeability of an intracellular aquaporin Nature. 1999;402:184-187.
  • Nemeth-Cahalan KL, Kalman K, Froger A, Hall JE. Zinc modulation of water permeability reveals that aquaporin 0 functions as a cooperative tetramer. J Gen Physiol 2007;130:457–464.
  • Chandy G, Zampighi GA, Kreman M, Hall JE. Comparison of the water transporting properties of MIP and AQP1. The Journal of membrane biology 1997;159:29-39.
  • Hamann S, Zeuthen T, La Cour M, et al. Aquaporins in complex tissues: distribution of aquaporins 1-5 in human and rat eye. Am J Physiol 1998;274:1332-1345.
  • Kenney MC, Atilano SR, Zorapapel N, Holguin B, Gaster RN, Ljubimov AV. Altered expression of aquaporins in bullous keratopathy and Fuchs’ dystrophy corneas. J. Histochem. Cytochem 2004;52:1341–1350.
  • Funaki H, Yamamoto T, Koyama Y et al. Localization and expression of AQP5 in cornea, serous salivary glands, and pulmonary epithelial cells. Am. J. Physiol 1998;275:1151–1157.
  • Tran TL, Bek T, la Cour M et al. Altered aquaporin expression in glaucoma eyes. APMIS 2014;122:772–780.
  • Tran TL, Bek T, Holm L, et al. Aquaporins 6-12 in the human eye. Acta Ophthalmol 2013;91:557–563.
  • Kumari SS, Varadaraj K. Aquaporin 5 knockout mouse lens develops hyperglycemic cataract. Biochemical and biophysical research communications 2013;441:333-338.
  • Agre P, King LS, Yasui M et al. Aquaporin water channels– from atomic structure to clinical medicine. The Journal of physiology 2002;542:3-16.
  • Varadaraj K, Kumari SS. Molecular mechanism of Aquaporin 0-induced fiber cell to fiber cell adhesion in the eye lens. Biochemical and biophysical research communications 2018;506:284-289.
  • Costello MJ, McIntosh TJ, Robertson, JD. Distribution of gap junctions and square array junctions in the mammalian lens. Investigative ophthalmology & visual science 1989;30:975-989.
  • Freites JA, Németh-Cahalan KL, Hall JE, Tobias DJ. Cooperativity and allostery in aquaporin 0 regulation by Ca2+. Biochimica et Biophysica Acta (BBA)-Biomembranes 2019;1861:988-996.
  • Zhang, D, Vetrivel, L, Verkman, AS. Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production. The Journal of general physiology 2022;119:561-569.
  • Delporte C. Aquaporins and gland secretion. Aquaporins 2017;969:63-79.
  • Delporte C, Soyfoo M. Aquaporins: Unexpected actors in autoimmune diseases. Autoimmunity Reviews 2022;21(8):103131.
  • Haydinger CD, Ferreira LB, Williams KA, Smith JR. Mechanisms of macular edema. Front Med (Lausanne) 2023;10:1128811.
  • Hashemi H, Pakzad R, Yekta A et al. Global and regional prevalence of age-related cataract: a comprehensive systematic review and meta-analysis. Eye 2020;34:1357-1370.
  • Ishida H, Shibata T, Nakamura Y et al. Identification of Differential Gene Expression Pattern in Lens Epithelial Cells Derived from Cataractous and Noncataractous Lenses of Shumiya Cataract Rat. BioMed research international 2020;2:7319590.
  • Barandika O, Ezquerra-Inchausti M, Anasagasti A et al. Increased aquaporin 1 and 5 membrane expression in the lens epithelium of cataract patients. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2016;1862:2015-2021.
  • Hayashi R, Hayashi S, Fukuda K, Sakai M, Machida S. Immunolocation of aquaporin 8 in human cataractous lenticular epithelial cells. Biomedicine hub 2018;2:1-5.
  • Huang OS, Seet LF, Ho HW et al. Altered iris aquaporin expression and aqueous humor osmolality in glaucoma. Investigative Ophthalmology & Visual Science 2021;62:34-34.
  • Tran, TL, Hamann S, Heegaard S. Aquaporins in the eye. Aquaporins 2017;193-198.
  • Lai Z, Yin H, Cabrera-Pérez J et al. Aquaporin gene therapy corrects Sjögren’s syndrome phenotype in mice. Proceedings of the National Academy of Sciences 2016;113:5694-5699.
  • Papadopoulos MC, Verkman A. Aquaporin 4 and neuromyelitis optica. The Lancet Neurology 2012;11:535-544.
There are 44 citations in total.

Details

Primary Language Turkish
Subjects Medical Pharmacology
Journal Section Review
Authors

Elif Karabacak 0000-0003-2054-4542

Bahadır Özelbaykal 0000-0001-5898-9016

Publication Date June 23, 2025
Submission Date August 14, 2024
Acceptance Date April 3, 2025
Published in Issue Year 2025 Volume: 7 Issue: 2

Cite

AMA Karabacak E, Özelbaykal B. Akuaporinlerin Gözdeki Değeri. Hitit Medical Journal. June 2025;7(2):280-288. doi:10.52827/hititmedj.1532970