LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp)

Ebbe Toftgaard Poulsen, Nadia Sukusu Nielsen, Morten M. Jensen, Esben Nielsen, Jesper Hjortdal, Eungkweon Kim, Jan J. Enghild

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

More than 60 mutations in transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after LASIK surgery, which may be important for the disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of LASIK surgery when compared to healthy individuals.

Original languageEnglish
Pages (from-to)539-543
Number of pages5
JournalProteomics
Volume16
Issue number3
DOIs
Publication statusPublished - 2016 Feb 1

Fingerprint

Laser In Situ Keratomileusis
Surgery
Lasers
Processing
Proteins
Extracellular Matrix Proteins
Mutation
Histidine
Amino Acid Substitution
Arginine
betaIG-H3 protein
Corneal dystrophy Avellino type
Labels
Immunoblotting
Cornea
Substitution reactions
Molecular weight
Disease Progression
Tissue
Molecular Weight

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Poulsen, Ebbe Toftgaard ; Nielsen, Nadia Sukusu ; Jensen, Morten M. ; Nielsen, Esben ; Hjortdal, Jesper ; Kim, Eungkweon ; Enghild, Jan J. / LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp). In: Proteomics. 2016 ; Vol. 16, No. 3. pp. 539-543.
@article{bf2ea788159d4e4bbdbad9a2b9a3e29a,
title = "LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp)",
abstract = "More than 60 mutations in transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after LASIK surgery, which may be important for the disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of LASIK surgery when compared to healthy individuals.",
author = "Poulsen, {Ebbe Toftgaard} and Nielsen, {Nadia Sukusu} and Jensen, {Morten M.} and Esben Nielsen and Jesper Hjortdal and Eungkweon Kim and Enghild, {Jan J.}",
year = "2016",
month = "2",
day = "1",
doi = "10.1002/pmic.201500287",
language = "English",
volume = "16",
pages = "539--543",
journal = "Proteomics",
issn = "1615-9853",
publisher = "Wiley-VCH Verlag",
number = "3",

}

LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp). / Poulsen, Ebbe Toftgaard; Nielsen, Nadia Sukusu; Jensen, Morten M.; Nielsen, Esben; Hjortdal, Jesper; Kim, Eungkweon; Enghild, Jan J.

In: Proteomics, Vol. 16, No. 3, 01.02.2016, p. 539-543.

Research output: Contribution to journalArticle

TY - JOUR

T1 - LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induced protein (TGFBIp)

AU - Poulsen, Ebbe Toftgaard

AU - Nielsen, Nadia Sukusu

AU - Jensen, Morten M.

AU - Nielsen, Esben

AU - Hjortdal, Jesper

AU - Kim, Eungkweon

AU - Enghild, Jan J.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - More than 60 mutations in transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after LASIK surgery, which may be important for the disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of LASIK surgery when compared to healthy individuals.

AB - More than 60 mutations in transforming growth factor beta-induced protein (TGFBIp) have been reported in humans causing a variety of phenotypic protein aggregates in the cornea, commonly termed corneal dystrophies. One mutation, generating an arginine to histidine amino acid substitution at position 124 in mature TGFBIp leads to granular corneal dystrophy type 2 (GCD2). Homozygous GCD2 cases develop massive protein accumulation early in life whereas heterozygous GCD2 cases become affected much later and generally with a much less severe outcome. However, if heterozygous GCD2 patients undergo laser-assisted in situ keratomileusis (LASIK) surgery protein accumulation is accelerated and they develop massive protein accumulations a few years after surgery. Here, we present the protein profile of aggregate-containing corneal tissue from GCD2 patients with a history of LASIK surgery using LC-MS/MS. Label-free quantification of corneal extracellular matrix proteins showed accumulation of TGFBIp. This was supported by 2DE and immunoblotting against TGFBIp that revealed the accumulation of full-length TGFBIp. In addition, a high molecular weight TGFBIp complex was more apparent in GCD2 patients after LASIK surgery, which may be important for the disease progression. Lastly, 2DE also revealed differential processing between GCD2 patients with a history of LASIK surgery when compared to healthy individuals.

UR - http://www.scopus.com/inward/record.url?scp=84958093615&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958093615&partnerID=8YFLogxK

U2 - 10.1002/pmic.201500287

DO - 10.1002/pmic.201500287

M3 - Article

C2 - 26864644

AN - SCOPUS:84958093615

VL - 16

SP - 539

EP - 543

JO - Proteomics

JF - Proteomics

SN - 1615-9853

IS - 3

ER -