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Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 11/2018

01-11-2018 | Refractive Surgery

Conjunctival MUC5AC+ goblet cell index: relationship with corneal nerves and dry eye

Authors: Cecilia Chao, Blanka Golebiowski, Fiona Stapleton, Xiangtian Zhou, Shihao Chen, Michele C. Madigan

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 11/2018

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Abstract

Purpose

To evaluate the relative proportion of conjunctival MUC5AC+ and MUC5AC− goblet cells in a post-LASIK population and their association with dry eye indicators and corneal nerve morphology using a MUC5AC+ Goblet Cell Index.

Methods

Twenty subjects who had undergone LASIK > 12 months previously and 20 age-matched controls were recruited. Dry eye symptoms, tear breakup time, osmolarity, meniscus area and corneal nerve morphology were examined. Conjunctival impression cytology samples were collected from inferior-temporal bulbar conjunctiva using Millicell® inserts. Total goblet cell density was determined from positive cytokeratin-7 (CK7) immunolabelling; MUC5AC+ goblet cell density was determined from both CK7+- and MUC5AC+-immunolabelled cells. The ratio of MUC5AC+ to total density was defined as the “MUC5AC+ Goblet Cell Index”. Differences in variables between groups and the associations between goblet cell variables and clinical assessments were examined.

Results

No significant differences in the total and MUC5AC+ goblet cell density and tear film parameters were found between groups, although greater ocular discomfort was reported in the post-LASIK group (P = 0.02). A higher MUC5AC+ Index was associated with worse/greater dry eye symptoms (ρ = 0.55, P = 0.01) and higher nerve tortuosity (ρ = 0.57, P = 0.01) in the post-LASIK group; lower nerve density and thickness was found in controls (ρ > −0.45, P < 0.05), but not associated with tear film parameters.

Conclusions

The MUC5AC+ Goblet Cell Index provides an indicator of mucin secretion for assessing the goblet cell function in dry eye. In the post-LASIK participants, we found an increased MUC5AC+ Index associated with worse dry eye symptoms and adverse changes in corneal nerve morphology.
Literature
1.
go back to reference Gipson IK (2016) Goblet cells of the conjunctiva: a review of recent findings. Prog Retin Eye Res 54:49–63CrossRef Gipson IK (2016) Goblet cells of the conjunctiva: a review of recent findings. Prog Retin Eye Res 54:49–63CrossRef
2.
go back to reference Gipson IK, Hori Y, Argueso P (2004) Character of ocular surface mucins and their alteration in dry eye disease. Ocul Surf 2:131–148CrossRef Gipson IK, Hori Y, Argueso P (2004) Character of ocular surface mucins and their alteration in dry eye disease. Ocul Surf 2:131–148CrossRef
3.
go back to reference Fleiszig SM, Zaidi TS, Ramphal R et al (1994) Modulation of pseudomonas aeruginosa adherence to the corneal surface by mucus. Infect Immunity 62:1799–1804 Fleiszig SM, Zaidi TS, Ramphal R et al (1994) Modulation of pseudomonas aeruginosa adherence to the corneal surface by mucus. Infect Immunity 62:1799–1804
4.
go back to reference Bron AJ, de Paiva CS, Chauhan SK et al (2017) TFOS DEWS II pathophysiology report. Ocul Surf 15:438–510CrossRef Bron AJ, de Paiva CS, Chauhan SK et al (2017) TFOS DEWS II pathophysiology report. Ocul Surf 15:438–510CrossRef
5.
go back to reference Lopin E, Deveney T, Asbell PA (2009) Impression cytology: recent advances and applications in dry eye disease. Ocul Surf 7:93–110CrossRef Lopin E, Deveney T, Asbell PA (2009) Impression cytology: recent advances and applications in dry eye disease. Ocul Surf 7:93–110CrossRef
6.
go back to reference Nelson JD, Havener VR, Cameron JD (1983) Cellulose acetate impressions of the ocular surface. Dry eye states Arch ophthalmol 101:1869–1872PubMed Nelson JD, Havener VR, Cameron JD (1983) Cellulose acetate impressions of the ocular surface. Dry eye states Arch ophthalmol 101:1869–1872PubMed
7.
go back to reference Kinoshita S, Kiorpes TC, Friend J et al (1983) Goblet cell density in ocular surface disease: a better indicator than tear mucin. Arch Ophthalmol 101:1284–1287CrossRef Kinoshita S, Kiorpes TC, Friend J et al (1983) Goblet cell density in ocular surface disease: a better indicator than tear mucin. Arch Ophthalmol 101:1284–1287CrossRef
8.
go back to reference Doughty MJ (2012) Goblet cells of the normal human bulbar conjunctiva and their assessment by impression cytology sampling. Ocul Surf 10:149–169CrossRef Doughty MJ (2012) Goblet cells of the normal human bulbar conjunctiva and their assessment by impression cytology sampling. Ocul Surf 10:149–169CrossRef
9.
go back to reference Albietz JM, Lenton LM, McLennan SG (2002) Effect of laser in situ keratomileusis for hyperopia on tear film and ocular surface. J Refract Surg 18:113–123PubMed Albietz JM, Lenton LM, McLennan SG (2002) Effect of laser in situ keratomileusis for hyperopia on tear film and ocular surface. J Refract Surg 18:113–123PubMed
10.
go back to reference Dogru M, Asano-Kato N, Tanaka M et al (2005) Ocular surface and muc5ac alterations in atopic patients with corneal shield ulcers. Curr Eye Res 30:897–908CrossRef Dogru M, Asano-Kato N, Tanaka M et al (2005) Ocular surface and muc5ac alterations in atopic patients with corneal shield ulcers. Curr Eye Res 30:897–908CrossRef
11.
go back to reference Ramamoorthy P, Nichols JJ (2008) Mucins in contact lens wear and dry eye conditions. Optom Vis Sci 85:631–642CrossRef Ramamoorthy P, Nichols JJ (2008) Mucins in contact lens wear and dry eye conditions. Optom Vis Sci 85:631–642CrossRef
12.
go back to reference Rodriguez AE, Rodriguez-Prats JL, Hamdi IM et al (2007) Comparison of goblet cell density after femtosecond laser and mechanical microkeratome in lasik. Invest Ophthalmol Vis Sci 48:2570–2575CrossRef Rodriguez AE, Rodriguez-Prats JL, Hamdi IM et al (2007) Comparison of goblet cell density after femtosecond laser and mechanical microkeratome in lasik. Invest Ophthalmol Vis Sci 48:2570–2575CrossRef
13.
go back to reference Ralph RA (1975) Conjunctival goblet cell density in normal subjects and in dry eye syndromes. Investig Ophthalmol 14:299–302 Ralph RA (1975) Conjunctival goblet cell density in normal subjects and in dry eye syndromes. Investig Ophthalmol 14:299–302
14.
go back to reference Argueso P, Balaram M, Spurr-Michaud S et al (2002) Decreased levels of the goblet cell mucin MUC5AC in tears of patients with sjogren syndrome. Invest Ophthalmol Vis Sci 43:1004–1011PubMed Argueso P, Balaram M, Spurr-Michaud S et al (2002) Decreased levels of the goblet cell mucin MUC5AC in tears of patients with sjogren syndrome. Invest Ophthalmol Vis Sci 43:1004–1011PubMed
15.
go back to reference Rodriguez-Prats JL, Hamdi IM, Rodriguez AE et al (2007) Effect of suction ring application during LASIK on goblet cell density. J Refract Surg 23:559–562PubMed Rodriguez-Prats JL, Hamdi IM, Rodriguez AE et al (2007) Effect of suction ring application during LASIK on goblet cell density. J Refract Surg 23:559–562PubMed
16.
go back to reference Shin SY, Lee YJ (2006) Conjunctival changes induced by LASIK suction ring in a rabbit model. Ophthalmic Res 38:343–349CrossRef Shin SY, Lee YJ (2006) Conjunctival changes induced by LASIK suction ring in a rabbit model. Ophthalmic Res 38:343–349CrossRef
17.
go back to reference Egbert PR, Lauber S, Maurice DM (1977) A simple conjunctival biopsy. Am J Ophthalmol 84:798–801CrossRef Egbert PR, Lauber S, Maurice DM (1977) A simple conjunctival biopsy. Am J Ophthalmol 84:798–801CrossRef
19.
go back to reference Moore JE, Vasey GT, Dartt DA et al (2011) Effect of tear hyperosmolarity and signs of clinical ocular surface pathology upon conjunctival goblet cell function in the human ocular surface. Invest Ophthalmol Vis Sci 52:6174–6180CrossRef Moore JE, Vasey GT, Dartt DA et al (2011) Effect of tear hyperosmolarity and signs of clinical ocular surface pathology upon conjunctival goblet cell function in the human ocular surface. Invest Ophthalmol Vis Sci 52:6174–6180CrossRef
20.
go back to reference Krenzer KL, Freddo TF (1997) Cytokeratin expression in normal human bulbar conjunctiva obtained by impression cytology. Invest Ophthalmol Vis Sci 38:142–152PubMed Krenzer KL, Freddo TF (1997) Cytokeratin expression in normal human bulbar conjunctiva obtained by impression cytology. Invest Ophthalmol Vis Sci 38:142–152PubMed
21.
go back to reference Ryan DS, Bower KS, Sia RK et al (2016) Goblet cell response after photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg 42:1181–1189CrossRef Ryan DS, Bower KS, Sia RK et al (2016) Goblet cell response after photorefractive keratectomy and laser in situ keratomileusis. J Cataract Refract Surg 42:1181–1189CrossRef
22.
go back to reference Jumblatt MM, McKenzie RW, Jumblatt JE (1999) MUC5AC mucin is a component of the human precorneal tear film. Invest Ophthalmol Vis Sci 40:43–49PubMed Jumblatt MM, McKenzie RW, Jumblatt JE (1999) MUC5AC mucin is a component of the human precorneal tear film. Invest Ophthalmol Vis Sci 40:43–49PubMed
23.
go back to reference He H, Ding H, Liao A et al (2010) Effects of mycophenolate mofetil on proliferation and mucin-5AC expression in human conjunctival goblet cells in vitro. Mol Vis 16:1913–1919PubMedPubMedCentral He H, Ding H, Liao A et al (2010) Effects of mycophenolate mofetil on proliferation and mucin-5AC expression in human conjunctival goblet cells in vitro. Mol Vis 16:1913–1919PubMedPubMedCentral
24.
go back to reference Eidet JR, Utheim OA, Raeder S et al (2012) Effects of serum-free storage on morphology, phenotype, and viability of ex vivo cultured human conjunctival epithelium. Exp Eye Res 94:109–116CrossRef Eidet JR, Utheim OA, Raeder S et al (2012) Effects of serum-free storage on morphology, phenotype, and viability of ex vivo cultured human conjunctival epithelium. Exp Eye Res 94:109–116CrossRef
25.
go back to reference Colorado LH, Pritchard N, Cronin BG et al (2016) Characterization of goblet cells in a pterygium biopsy using laser scanning confocal microscopy and immunohistochemistry. Cornea 35:1127–1131CrossRef Colorado LH, Pritchard N, Cronin BG et al (2016) Characterization of goblet cells in a pterygium biopsy using laser scanning confocal microscopy and immunohistochemistry. Cornea 35:1127–1131CrossRef
26.
go back to reference Chao C, Golebiowski B, Zhao X et al (2016) Long-term effects of LASIK on corneal innervation and tear neuropeptides and the associations with dry eye. J Refract Surg 32:518–524CrossRef Chao C, Golebiowski B, Zhao X et al (2016) Long-term effects of LASIK on corneal innervation and tear neuropeptides and the associations with dry eye. J Refract Surg 32:518–524CrossRef
27.
go back to reference Chao C, Golebiowski B, Cui Y et al (2014) Development of a Chinese version of the ocular comfort index. Invest Ophthalmol Vis Sci 55:3562–3571CrossRef Chao C, Golebiowski B, Cui Y et al (2014) Development of a Chinese version of the ocular comfort index. Invest Ophthalmol Vis Sci 55:3562–3571CrossRef
28.
go back to reference Chen F, Shen M, Chen W et al (2010) Tear meniscus volume in dry eye after punctal occlusion. Invest Ophthalmol Vis Sci 51:1965–1969CrossRef Chen F, Shen M, Chen W et al (2010) Tear meniscus volume in dry eye after punctal occlusion. Invest Ophthalmol Vis Sci 51:1965–1969CrossRef
29.
go back to reference Jalbert I, Madigan MC, Shao M et al (2012) Assessing the human lid margin epithelium using impression cytology. Acta Ophthalmol 90:e547–e552CrossRef Jalbert I, Madigan MC, Shao M et al (2012) Assessing the human lid margin epithelium using impression cytology. Acta Ophthalmol 90:e547–e552CrossRef
30.
go back to reference Chao C, Stapleton F, Zhou X et al (2015) Structural and functional changes in corneal innervation after laser in situ keratomileusis and their relationship with dry eye signs and symptoms. Graefe's Arch Clin Exp Ophthalmol 253:2029–2039CrossRef Chao C, Stapleton F, Zhou X et al (2015) Structural and functional changes in corneal innervation after laser in situ keratomileusis and their relationship with dry eye signs and symptoms. Graefe's Arch Clin Exp Ophthalmol 253:2029–2039CrossRef
31.
go back to reference Contreras-Ruiz L, Ghosh-Mitra A, Shatos MA et al (2013) Modulation of conjunctival goblet cell function by inflammatory cytokines. Med Inf 2013:636812 Contreras-Ruiz L, Ghosh-Mitra A, Shatos MA et al (2013) Modulation of conjunctival goblet cell function by inflammatory cytokines. Med Inf 2013:636812
32.
go back to reference He M, Storr-Paulsen T, Wang AL et al (2016) Artificial polymeric scaffolds as extracellular matrix substitutes for autologous conjunctival goblet cell expansion. Invest Ophthalmol Vis Sci 57:6134–6146CrossRef He M, Storr-Paulsen T, Wang AL et al (2016) Artificial polymeric scaffolds as extracellular matrix substitutes for autologous conjunctival goblet cell expansion. Invest Ophthalmol Vis Sci 57:6134–6146CrossRef
33.
go back to reference Moore CP, Wilsman NJ, Nordheim EV et al (1987) Density and distribution of canine conjunctival goblet cells. Invest Ophthalmol Vis Sci 28:1925–1932PubMed Moore CP, Wilsman NJ, Nordheim EV et al (1987) Density and distribution of canine conjunctival goblet cells. Invest Ophthalmol Vis Sci 28:1925–1932PubMed
34.
go back to reference Kato K, Miyake K, Kondo N et al (2017) Conjunctival goblet cell density following cataract surgery with diclofenac versus diclofenac and rebamipide: a randomized trial. Am J Ophthalmol 181:26–36CrossRef Kato K, Miyake K, Kondo N et al (2017) Conjunctival goblet cell density following cataract surgery with diclofenac versus diclofenac and rebamipide: a randomized trial. Am J Ophthalmol 181:26–36CrossRef
35.
go back to reference Albietz JM, McLennan SG, Lenton LM (2003) Ocular surface management of photorefractive keratectomy and laser in situ keratomileusis. J Refract Surg 19:636–644PubMed Albietz JM, McLennan SG, Lenton LM (2003) Ocular surface management of photorefractive keratectomy and laser in situ keratomileusis. J Refract Surg 19:636–644PubMed
36.
go back to reference Konomi K, Chen LL, Tarko RS et al (2008) Preoperative characteristics and a potential mechanism of chronic dry eye after lasik. Invest Ophthalmol Vis Sci 49:168–174CrossRef Konomi K, Chen LL, Tarko RS et al (2008) Preoperative characteristics and a potential mechanism of chronic dry eye after lasik. Invest Ophthalmol Vis Sci 49:168–174CrossRef
37.
go back to reference Kessler TL, Mercer HJ, Zieske JD et al (1995) Stimulation of goblet cell mucous secretion by activation of nerves in rat conjunctiva. Curr Eye Res 14:985–992CrossRef Kessler TL, Mercer HJ, Zieske JD et al (1995) Stimulation of goblet cell mucous secretion by activation of nerves in rat conjunctiva. Curr Eye Res 14:985–992CrossRef
38.
go back to reference Chao C, Golebiowski B, Stapleton F (2014) The role of corneal innervation in LASIK-induced neuropathic dry eye. Ocul Surf 12:32–45CrossRef Chao C, Golebiowski B, Stapleton F (2014) The role of corneal innervation in LASIK-induced neuropathic dry eye. Ocul Surf 12:32–45CrossRef
39.
go back to reference Diebold Y, Rios JD, Hodges RR et al (2001) Presence of nerves and their receptors in mouse and human conjunctival goblet cells. Invest Ophthalmol Vis Sci 42:2270–2282PubMed Diebold Y, Rios JD, Hodges RR et al (2001) Presence of nerves and their receptors in mouse and human conjunctival goblet cells. Invest Ophthalmol Vis Sci 42:2270–2282PubMed
40.
go back to reference Kato K, Takashima Y, Matsunaga K et al (2016) Effect of topical rebamipide on conjunctival goblet cell recovery after vitrectomy. Sci Rep 6:19516CrossRef Kato K, Takashima Y, Matsunaga K et al (2016) Effect of topical rebamipide on conjunctival goblet cell recovery after vitrectomy. Sci Rep 6:19516CrossRef
41.
go back to reference Peral A, Pintor J (2008) Ocular mucin visualization by confocal laser scanning microscopy. Cornea 27:395–401CrossRef Peral A, Pintor J (2008) Ocular mucin visualization by confocal laser scanning microscopy. Cornea 27:395–401CrossRef
42.
go back to reference Doughty MJ (2016) Giemsa-based cytological assessment of area, shape and nucleus:cytoplasm ratio of goblet cells of rabbit bulbar conjunctiva. Biotech Histochem 91:501–509CrossRef Doughty MJ (2016) Giemsa-based cytological assessment of area, shape and nucleus:cytoplasm ratio of goblet cells of rabbit bulbar conjunctiva. Biotech Histochem 91:501–509CrossRef
Metadata
Title
Conjunctival MUC5AC+ goblet cell index: relationship with corneal nerves and dry eye
Authors
Cecilia Chao
Blanka Golebiowski
Fiona Stapleton
Xiangtian Zhou
Shihao Chen
Michele C. Madigan
Publication date
01-11-2018
Publisher
Springer Berlin Heidelberg
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 11/2018
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-018-4065-y

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