Top

International Ophthalmology

Published in:

01-12-2024 | Original Paper

High-throughput screening of transient receptor potential (TRP) channels in pterygium

Authors: Yusuf Tuylu, Seydi Okumus, Rauf Gul, Ibrahim Erbagci

Published in: International Ophthalmology | Issue 1/2024

Abstract

Purpose

Pterygium is a hyaline degenerative disease of the conjunctiva characterized by the progression of fibrovascular connective tissue from the bulbar conjunctiva to the cornea. The mechanism of pterygium formation is still not fully understood. Transient receptor potential (TRP) channels are a group of ion channels with distinct characteristics. Recent indications suggest TRP channels may play a significant regulatory role in pterygium development, but previous studies have mainly focused on in silico analysis. Accordingly, in the present study, we aimed to decipher the expression signatures and role of TRP channels in pterygium development.

Methods

The study encompassed a cohort of 45 patients matched for age and gender distribution, comprising 30 individuals with primary pterygium (PP) and 15 individuals with recurrent pterygium (RP). The control group consisted of unaffected conjunctival tissue obtained from the same set of patients. High-throughput screening of differentially expressed TRP channels in pterygium tissues was achieved with the help of Fluidigm 96.96 Dynamic Array Expression Chip and reactions were held in BioMark™ HD System Real-Time PCR platform.

Results

Statistically significant increases were found in the expression of 21 genes, mainly TRPA1 (p = 0.021), TRPC2 (p = 0.001), and TRPM8 (p = 0.003), in patients with PP, and in TRPC5 (p = 0.05), TRPM2 (p = 0.029), TRPM4 (p = 0.03), TRPM6 (p = 0.045), TRPM8 (p = 0.038), TRPV1 (p = 0.01) and TRPV4 (p = 0.025) genes in RP tissues.

Conclusion

Collectively, TRP channel proteins appear to play pivotal roles in both the development and progression of pterygium, making them promising candidates for future therapeutic interventions in patients afflicted by this condition.

Shahraki T, Arabi A, Feizi S (2021) Pterygium: an update on pathophysiology, clinical features, and management. Ther Adv Ophthalmol 13:25158414211020150PubMedPubMedCentral

Shiroma H, Higa A, Sawaguchi S, Iwase A, Tomidokoro A, Amano S, Araie M (2009) Prevalence and risk factors of pterygium in a southwestern island of Japan: the Kumejima Study. Am J Ophthalmol 148:766-771.e761. https://doi.org/10.1016/j.ajo.2009.06.006CrossRefPubMed

McCarty CA, Fu CL, Taylor HR (2000) Epidemiology of pterygium in Victoria, Australia. Br J Ophthalmol 84:289–292. https://doi.org/10.1136/bjo.84.3.289CrossRefPubMedPubMedCentral

Wang IJ, Hu FR, Chen PJ, Lin CT (2000) Mechanism of abnormal elastin gene expression in the pinguecular part of pterygia. Am J Pathol 157:1269–1276. https://doi.org/10.1016/s0002-9440(10)64642-1CrossRefPubMedPubMedCentral

Hu Q, Qiao Y, Nie X, Cheng X, Ma Y (2014) Bevacizumab in the treatment of pterygium: a meta-analysis. Cornea 33:154–160. https://doi.org/10.1097/ico.0000000000000037CrossRefPubMed

Tsai YY, Chiang CC, Yeh KT, Lee H, Cheng YW (2010) Effect of TIMP-1 and MMP in pterygium invasion. Invest Ophthalmol Vis Sci 51:3462–3467. https://doi.org/10.1167/iovs.09-4921CrossRefPubMed

Liang K, Jiang Z, Ding BQ, Cheng P, Huang DK, Tao LM (2011) Expression of cell proliferation and apoptosis biomarkers in pterygia and normal conjunctiva. Mol Vis 17:1687–1693PubMedPubMedCentral

Ang LP, Chua JL, Tan DT (2007) Current concepts and techniques in pterygium treatment. Curr Opin Ophthalmol 18:308–313. https://doi.org/10.1097/ICU.0b013e3281a7ecbbCrossRefPubMed

Clapham DE (2003) TRP channels as cellular sensors. Nature 426:517–524. https://doi.org/10.1038/nature02196CrossRefPubMedADS

10.

Devi S, Kedlaya R, Maddodi N, Bhat KM, Weber CS, Valdivia H, Setaluri V (2009) Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light. Am J Physiol Cell Physiol 297:C679-687. https://doi.org/10.1152/ajpcell.00092.2009CrossRefPubMedPubMedCentral

11.

Masumoto K, Tsukimoto M, Kojima S (2013) Role of TRPM2 and TRPV1 cation channels in cellular responses to radiation-induced DNA damage. Biochem Biophys Acta 1830:3382–3390. https://doi.org/10.1016/j.bbagen.2013.02.020CrossRefPubMed

12.

Tsai YY, Cheng YW, Lee H, Tsai FJ, Tseng SH, Lin CL, Chang KC (2005) Oxidative DNA damage in pterygium. Mol Vis 11:71–75PubMed

13.

Shen A, Ye Y, Wang X, Chen C, Zhang H, Hu J (2005) Raman scattering properties of human pterygium tissue. J Biomed Opt 10:024036. https://doi.org/10.1117/1.1888345CrossRefPubMed

14.

Chen SJ, Zhang W, Tong Q, Conrad K, Hirschler-Laszkiewicz I, Bayerl M, Kim JK, Cheung JY, Miller BA (2013) Role of TRPM2 in cell proliferation and susceptibility to oxidative stress. Am J Physiol Cell Physiol 304:C548-560. https://doi.org/10.1152/ajpcell.00069.2012CrossRefPubMedPubMedCentral

15.

Nazıroğlu M, Dikici DM, Dursun S (2012) Role of oxidative stress and Ca²⁺ signaling on molecular pathways of neuropathic pain in diabetes: focus on TRP channels. Neurochem Res 37:2065–2075. https://doi.org/10.1007/s11064-012-0850-xCrossRefPubMed

16.

Gao H, Chen X, Du X, Guan B, Liu Y, Zhang H (2011) EGF enhances the migration of cancer cells by up-regulation of TRPM7. Cell Calcium 50:559–568. https://doi.org/10.1016/j.ceca.2011.09.003CrossRefPubMed

17.

Maini R, Collison DJ, Maidment JM, Davies PD, Wormstone IM (2002) Pterygial derived fibroblasts express functionally active histamine and epidermal growth factor receptors. Exp Eye Res 74:237–244. https://doi.org/10.1006/exer.2001.1116CrossRefPubMed

18.

Cai Y, Zhou T, Chen J, Cai X, Fu Y (2023) Uncovering the role of transient receptor potential channels in pterygium: a machine learning approach. Inflamm Res 72:589–602. https://doi.org/10.1007/s00011-023-01693-4CrossRefPubMed

19.

Kaneko Y, Szallasi A (2014) Transient receptor potential (TRP) channels: a clinical perspective. Br J Pharmacol 171:2474–2507. https://doi.org/10.1111/bph.12414CrossRefPubMedPubMedCentral

20.

Touyz RM (2008) Transient receptor potential melastatin 6 and 7 channels, magnesium transport, and vascular biology: implications in hypertension. Am J Physiol Heart Circ Physiol 294:H1103-1118. https://doi.org/10.1152/ajpheart.00903.2007CrossRefPubMed

21.

Alptekin M, Eroglu S, Tutar E, Sencan S, Geyik MA, Ulasli M, Demiryurek AT, Camci C (2015) Gene expressions of TRP channels in glioblastoma multiforme and relation with survival. Tumour Biol J Int Soc Oncodev Biol Med 36:9209–9213. https://doi.org/10.1007/s13277-015-3577-xCrossRef

22.

Liu T, Fang Z, Wang G, Shi M, Wang X, Jiang K, Yang Z, Cao R, Tao H, Wang X, Zhou J (2016) Anti-tumor activity of the TRPM8 inhibitor BCTC in prostate cancer DU145 cells. Oncol Lett 11:182–188. https://doi.org/10.3892/ol.2015.3854CrossRefPubMed

23.

Nilius B, Flockerzi V (2014) Mammalian transient receptor potential (TRP) cation channels. Preface Handb Exp Pharmacol 223:v–viPubMed

24.

Dehkordi O, Rose JE, Fatemi M, Allard JS, Balan KV, Young JK, Fatima S, Millis RM, Jayam-Trouth A (2012) Neuronal expression of bitter taste receptors and downstream signaling molecules in the rat brainstem. Brain Res 1475:1–10. https://doi.org/10.1016/j.brainres.2012.07.038CrossRefPubMed

25.

Okumus S, Demiryürek S, Gürler B, Coskun E, Bozgeyik I, Oztuzcu S, Kaydu E, Celik O, Erbagcı I, Demiryürek AT (2013) Association transient receptor potential melastatin channel gene polymorphism with primary open angle glaucoma. Mol Vis 19:1852–1858PubMedPubMedCentral

26.

Lam DS, Wong AK, Fan DS, Chew S, Kwok PS, Tso MO (1998) Intraoperative mitomycin C to prevent recurrence of pterygium after excision: a 30-month follow-up study. Ophthalmology 105:901–904; discussion 904–905. https://doi.org/10.1016/s0161-6420(98)95034-5

27.

Dorovkov MV, Ryazanov AG (2004) Phosphorylation of annexin I by TRPM7 channel-kinase. J Biol Chem 279:50643–50646. https://doi.org/10.1074/jbc.C400441200CrossRefPubMed

28.

Thebault S, Flourakis M, Vanoverberghe K, Vandermoere F, Roudbaraki M, Lehen’kyi V, Slomianny C, Beck B, Mariot P, Bonnal JL, Mauroy B, Shuba Y, Capiod T, Skryma R, Prevarskaya N (2006) Differential role of transient receptor potential channels in Ca2+ entry and proliferation of prostate cancer epithelial cells. Can Res 66:2038–2047. https://doi.org/10.1158/0008-5472.Can-05-0376CrossRef

29.

Faouzi M, Penner R (2014) TRPM2. Handb Exp Pharmacol 222:403–426. https://doi.org/10.1007/978-3-642-54215-2_16CrossRefPubMed

30.

Perraud AL, Knowles HM, Schmitz C (2004) Novel aspects of signaling and ion-homeostasis regulation in immunocytes. The TRPM ion channels and their potential role in modulating the immune response. Mol Immunol 41:657–673. https://doi.org/10.1016/j.molimm.2004.04.013CrossRefPubMed

31.

Oancea E, Vriens J, Brauchi S, Jun J, Splawski I, Clapham DE (2009) TRPM1 forms ion channels associated with melanin content in melanocytes. Sci Signal 2:ra21. https://doi.org/10.1126/scisignal.2000146CrossRefPubMedPubMedCentral

32.

van Genderen MM, Bijveld MM, Claassen YB, Florijn RJ, Pearring JN, Meire FM, McCall MA, Riemslag FC, Gregg RG, Bergen AA, Kamermans M (2009) Mutations in TRPM1 are a common cause of complete congenital stationary night blindness. Am J Hum Genet 85:730–736. https://doi.org/10.1016/j.ajhg.2009.10.012CrossRefPubMedPubMedCentral

33.

İlhan HD, Ünal B, Ayaz Y, Erin N (2022) Changes in TRPV1 expression as well as substance P and vasoactive intestinal peptide levels are associated with recurrence of pterygium. Int J Mol Sci 23:15692CrossRefPubMedPubMedCentral

Title: High-throughput screening of transient receptor potential (TRP) channels in pterygium
Authors: Yusuf Tuylu
Seydi Okumus
Rauf Gul
Ibrahim Erbagci
Publication date: 01-12-2024
Publisher: Springer Netherlands
Published in: International Ophthalmology / Issue 1/2024
Print ISSN: 0165-5701
Electronic ISSN: 1573-2630
DOI: https://doi.org/10.1007/s10792-024-02938-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

High-throughput screening of transient receptor potential (TRP) channels in pterygium

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2024

Anterior chamber flare and choroidal vascular index as inflammatory markers after uncomplicated phacoemulsification surgery

Cataract surgery with new monofocal intraocular lens enhanced for intermediate vision and standard monofocal intraocular lens for retinal disorder

Comparison of preoperative prophylaxis with povidone–iodine (5%) and moxifloxacin (0.5%) versus povidone–iodine (5%) alone: a prospective study from India

Ocular injuries associated with motor vehicle accidents: long term effects on quality of life

Accuracy of intraocular lens formulas in combined phacovitrectomy

Subthreshold micropulse diode laser treatment in diabetic macular edema: biological impact, therapeutic effects, and safety