A New Ophthalmic Pharmaceutical Formulation, Topical Sulglycotide, Enhances the Ocular Mucin Secretion in Desiccation Stress-Mediated Dry Eye Disease

被引:15
作者
Lee, Hyesook [1 ]
Jeon, Sangwon [2 ]
Kim, Chae Eun [1 ]
Park, Young-Joon [2 ]
Yang, Jaewook [1 ,3 ]
机构
[1] Inje Univ, Busan Paik Hosp, T2B Infrastruct Ctr Ocular Dis, Busan, South Korea
[2] Ajou Univ, Coll Pharm, 206 World Cup Ro, Suwon 16499, South Korea
[3] Inje Univ, Coll Med, Dept Ophthalmol, 75 Bokji Ro, Busan 47392, South Korea
关键词
dry eye disease; sulglycotide (SOS); mucin; conjunctival goblet cell; inflammation; TEAR-FILM; BARRIER DISRUPTION; CORNEAL; GLYCOPROTEIN; EXPRESSION; RESISTANCE; SURFACE; INS365;
D O I
10.1167/iovs.18-24935
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE. The aim of this study was the investigation of the effect of sulglycotide (SOS), a polysulfated glycopeptide derived from porcine duodenal mucin, for the treatment of dry eye disease. METHODS. NOD.B10.H2(b) mice were exposed to an air draft for 10 days, and, simultaneously, scopolamine hydrobromide was injected subcutaneously. The mice were randomly divided into nine groups as follows: four kinds of SOS formulations and three kinds of commercial medicine. After 10 days of treatment, we estimated the effect of treatment on tear production, epithelium stabilization, mucin secretion, and inflammation. RESULTS. The desiccation stress significantly decreased tear production and corneal epithelium stabilization, as well as markedly decreased the numbers of goblet cells and mucin-stained cells in conjunctiva. However, the topical 4% SOS eye drops markedly increased tear production and corneal stabilization, which recovered to baseline levels. In addition, topical 4% SOS significantly induced an increase in the numbers of goblet cells and the expression of membrane-associated mucins including MUC1, MUC4, and MUC16, as well as the gel-forming mucin, MUC5AC. Furthermore, SOS formulations provided anti-inflammatory improvement in a dose-dependent manner. CONCLUSIONS. In summary, we suggest that a new ophthalmic pharmaceutical formulation, topical sulglycotide, enhances the ocular mucin secretion in dry eye disease and can be used as a new ophthalmic pharmaceutical material to treat dry eye disease.
引用
收藏
页码:1076 / 1087
页数:12
相关论文
共 45 条
[1]  
Argüeso P, 2002, INVEST OPHTH VIS SCI, V43, P1004
[2]  
BERTELLINI G, 1971, ARZNEI-FORSCHUNG, V21, P244
[3]   Pharmacokinetic evaluation of diquafosol tetrasodium for the treatment of Sjogren's syndrome [J].
Bremond-Gignac, Dominique ;
Gicquel, Jean-Jacques ;
Chiambaretta, Frederic .
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY, 2014, 10 (06) :905-913
[4]   TFOS DEWS II pathophysiology report [J].
Bron, Anthony J. ;
de Paiva, Cintia S. ;
Chauhan, Sunil K. ;
Bonini, Stefano ;
Gabison, Eric E. ;
Jain, Sandeep ;
Knop, Erich ;
Markoulli, Maria ;
Ogawa, Yoko ;
Perez, Victor ;
Uchino, Yuichi ;
Yokoi, Norihiko ;
Zoukhri, Driss ;
Sullivan, David A. .
OCULAR SURFACE, 2017, 15 (03) :438-510
[5]   STUDIES ON POSSIBLE ABSORPTION OF A SULFATED GLYCOPEPTIDE (GLPS) IN RELATION TO ITS MODE OF ACTION [J].
CHASSEAUD, LF ;
SAGGERS, VH ;
SWORD, IP ;
FRY, BJ ;
HATHWAY, DE .
BIOCHEMICAL PHARMACOLOGY, 1972, 21 (23) :3121-+
[6]   TFOS DEWS II Definition and Classification Report [J].
Craig, Jennifer P. ;
Nichols, Kelly K. ;
Akpek, Esen K. ;
Caffery, Barbara ;
Dua, Harminder S. ;
Joo, Choun-Ki ;
Liu, Zuguo ;
Nelson, J. Daniel ;
Nichols, Jason J. ;
Tsubota, Kazuo ;
Stapleton, Fiona .
OCULAR SURFACE, 2017, 15 (03) :276-283
[7]  
Danjo Y, 1998, INVEST OPHTH VIS SCI, V39, P2602
[8]   Apical corneal barrier disruption in experimental murine dry eye is abrogated by methylprednisolone and doxycycline [J].
De Paiva, Cintia S. ;
Corrales, Rosa M. ;
Villarreal, Arturo L. ;
Farley, William ;
Li, De-Quan ;
Stern, Michael E. ;
Pflugfelder, Stephen C. .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (07) :2847-2856
[9]   The Effect of Hormone Replacement Therapy on Dry Eye Syndrome Evaluated with Schirmer Test and Break-Up Time [J].
Feng, Yanhong ;
Feng, Gang ;
Peng, Shuli ;
Li, Hui .
JOURNAL OF OPHTHALMOLOGY, 2015, 2015
[10]   INS365 suppresses, epithelial integrity loss of corneal by secretion of mucin-like glycoprotein in a rabbit short-term dry eye model [J].
Fujihara, T ;
Murakami, T ;
Nagano, T ;
Nakamura, M ;
Nakata, K .
JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS, 2002, 18 (04) :363-370