The mucin 5 AC level in medical faculty students with Computer Vision Syndrome ( CVS )

Introduction: Prolonged computer use will lead to a group of symptoms such as dryness of eyes, tired, headache and others called Computer Vision Syndrome (CVS). The decrease of Mucin 5 AC (MUC5AC) level could be one of the signs of dry eye disease on persons with CVS. Objective: The purpose of this study is to describe the Mucin 5AC level in medical faculty students of Udayana University, Bali, Indonesia


INTRODUCTION
Tear layers consist of three layers, which are lipid layer at the outer part, aqueous layer at the middle part and mucin layer at the inner part of the tears.Mucin plays an important role in maintaining ocular surface health.The mucin layer is produced by conjunctival goblet cells, corneal conjunctival epithelial, and lacrimal gland.Disturbance in the mucin production and mucin stability will lead to the Dry Eye Disease (DED) and affects the quality of life. 1 Mucin is a large negativity glycoprotein.Mucin forms the deepest and closest layer to the surface of the cornea and directly interacts with conjunctival glycocalyx, giving a hydrophilic layer to the aquous layer.The hydrophilic characteristic of mucin helps to distribute aquous on the ocular surface.Mucin layer also interacts with the lipid layer to reduce the ocular tear surface tension make the layer more stable.In addition the mucin layer can also takes the surface cells of the oculating peels, foreign objects and bacteria through loose mucin tissue that covers the bulbi conjunctival.The mucin layer also lubricates the eyelids when the layer passes through the eyeball.Conjunctival goblet cells responsible for mucin production are located on the apical surface of the conjunctiva, including interspersed with several layers of stratified epithelium. 5Meanwhile, stratified epithelial cells produce trans membrane mucins such as MUC1 and MUC4. 5 Among all mucin gel, MUC 2, MUC5AC and MUC 19 can be detected in human conjunctival tissue and MUC 5 AC is the most gelatinous mucin found in the eye. 6,7,8eficiency of secretions and expression of mucin genes in the conjunctival cell was found in disorders of the ocular surface associated with DED.Many studies of the deficiency and disorders of glycosylation Mucin (MUC5AC and MUC 2) that have been reported were found in Sjogren Syndrome and Non Sjogren Syndrome types of DED. 9 The study by Argüeso et al., 2002 showed that there was a significant decrease in MUC5AC transcription in DED patients' conjunctival due to Sgrögren Syndrome than in normal individuals, while decreased in the expression of MUC1 and MUC4 was not found. 5he study by Berry et al., 2008 also showed a decrease in MUC5AC levels in DED.MUC16 and MUC5AC are also associated with corneal staining shows if there is ocular surface damage. 10he widely use of computer in young age will affect ocular surface condition including mucin tear's level.Studies of MUC5AC levels in tears

METHODS
This study is an observational cross-sectional analytic study at Medical Faculty Udayana University carried out 34 samples with the permission of ethical clearance from the Health Research Ethics Commission, Faculty of Medicine, Udayana University.The study was conducted in October 2018.Samples were medical student of Medical Faculty Udayana University which collected by purposive sampling after fulfilling the inclusion and exclusion criteria.The inclusion criteria were those Schirmer test result ≥ 15 mm, willing to take part for tears examination, and sign the informed consent.Exclusion criteria were respondents with routine contact lens used, pregnancy or breast feeding, respondents who have treated by LASIK procedure, infected eye, and respondents with history of fluorescein allergy.
All samples were given questionnaire, underwent interviewed, ophthalmology examination, and tears biochemistry examination.The samples were devided into CVS and Non CVS group based on the qustionnaire scores that resembles CVS symptoms.Thirty four subject selected by consecutive sampling were examined with Schirmer I test, Tear Break Up time (TBUT) test, and Mucin 5AC test by ELISA procedure.
Tear samples collection were using Schirmer's strip (Tear Flow Diagnostic Test Strip; Rancho Cucamonga, CA) that placed at the temporal canthus of each eye for 5 minutes without anesthetic.The strips were then removed from the eyes, and the amount of wetting in millimeters was recorded by observing the edge of moisture on the printed millimeter marks.Strips were placed on centrifuge tube and run for 5 minutes of 12.000 RPM centrifuge to get the tears and stored in -20°C until all samples collected.ELISA procedure were performed at Biochemistry Laboratory of Udayana University.Data analysis used crosstabulation table and chi-square test.Significance was stated at p <0.05.

RESULTS
The study sample consisted of 34 respondents of Medical Faculty students, Udayana University in period class of 2015-2016.There were 21 CVS samples and 13 Non-CVS samples based on symptoms that recordec from the questionnaire.All the samples examined by Schirmer I test, TBUT, and MUC5AC levels test.
Table 1 shows that the subjects were dominated by female (24 subjects or 70.6%) and 10 subjects (29.4%) were male.The mean age of subjects was 20.09 ± 0.71 years old.Schirmer test examined in both eyes (left and right) and presented in the  The Mucin 5AC concentration level and chi-square test result presented in table 2. The statistic test result showed, this is significant correlation between Mucin 5AC level with CVS.The odd ratio result is 6.8 with 1.42 -32.37 confidence interval, identified as subjects with low mucin levels have a risk 6.8 times greater to experience CVS (OR = 6.8; 95% CI = 1.42-32.37;p = 0.012) than subjects with normal mucin 5AC level.The table 2 is listed below:

DISCUSSION
This study found that the research subjects were dominated by female (70.6%) and 10 subjects (29.4%) were male.The proportion of male and female subjects in the medical students of class period 2015-2016 is equivalence.In this study the percentage of samples with CVS was more female (76.2%) than men.Study by Tornqvist et al among professional computer users showed that women had higher risk of acquiring eye symptoms than men. 10 These symptoms could be caused by indoors activities using gadgets in women students may be longer than men students, tendendy to stay in cool environment with air conditioner in the room, the use of eye make up that can be have influence on the tears so the possibility of CVS is higher in women students than in men students.
Mean age of the subjects who participated in this study was 20.09 ± 0.71 years old who were in productive age and many activities in that age group that used computers or video display terminals (VDT).Similar resuts were found in other Asian population such as in India 11 and in Japan. 12BUT values are usually low in cases of evaporative dry eyes.Research by Goto et al. (2008) reported TBUT values of 3.4 ± 2.4 seconds in evaporative dry eye cases. 13In this study the mean standard deviation of the right eye TBUT value was 11.32 + 4.47 second, while the left eye was 11.29 + 4.34 second. Meanwhile, research conducted by Zhao H et al (2001) reported no association between mucin level 5AC and age or sex in healthy communities. 15he study by Argueso et al. found that the amount of mucin 5AC in tears that could be detected by ELISA varied between 1-5 to 1-9 ng/ per mg of protein in normal subjects. 5Zhao et al. 15 found that levels MUC 5AC in humans ranges from undetectable to 200 ng / mL.MUC 5AC levels in tears measured by ELISA around 6.8 ng/ mg in normal eye. 15In this study the mean value with a standard deviation of mucin 5AC levels was 183.95 ± 71.99 ng/ml.The mucin levels in the study sample were still within normal limits but tended to decrease in samples experiencing CVS.Deficiency of the secretions and expression of mucin 5AC genes in the conjunctival epithelium usually found in ocular surface disorder associated with dry eye as a symptom of CVS. 16,17A total of 17 samples of this study experienced CVS and had decreased mucin levels and were categorized as low mucin while 4 were normal mucin categories.
This study was conducted in relatively younger age that still have normal Schirmer and TBUT test.The small samples and CVS that assessed by the symptoms only and not resembels the DED were the limitation of this study.But this study can show a prediction that Mucin 5 AC level tend to decrease in young people who frequently use computer more than 4 hours eventough no clinical signs and symptoms of DED were reported.

CONCLUSION
There is significant association between low level of mucin 5AC and the risk of CVS in the medical students with prolonged computer use.Students with low level of mucin 5AC is 6.8 times tend to experience CVS than students with normal mucin 5AC level.Further mucin 5AC study with larger sample size and older age is needed to prove the role mucin 5AC as one of CVS risk factor.

2,3,4
at young age have never been reported in Bali and in Indonesia.This makes the researchers investigate the level of MUC5AC at a young age, especially in medical students who frequently use computer and experience symptoms of CVS. especially

table 1 .
The mean value of Schirmer I test result on right eye was 33.47 ± 4.29 mm, while Schirmer I test result on left eye was 33.00 ± 4.25 mm.Tear break up time test also performed in both eyes.

Tabel 2 Low level of Mucin 5AC as The Risk Factor for CVS
*significance (p < 0.05)

Table 1 Characteristics of Research subject Variable Result
TBUT: tear break up time; OD: oculi dextra; OS: oculi sinistra; DS : deviation standard ORIGINAL ARTICLE