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1 대한안과학회지 2016 년제 57 권제 4 호 J Korean Ophthalmol Soc 2016;57(4): ISSN (Print) ISSN (Online) Original Article 녹내장환자의방수내사이토카인농도분석 Elevated Matrix Metalloproteinase in Aqueous Humor in Patients with Open-Angle Glaucoma 김효원 지동현 최진아 Hyo Won Kim, MD, Dong Hyun Jee, MD, Jin A Choi, MD, PhD 가톨릭대학교의과대학성빈센트병원안과및시과학교실 Department of Ophthalmology and Visual Science, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea Purpose: To compare the aqueous concentrations of cytokines in glaucomatous eyes with those of normal controls and to characterize the clinical factors associated with aqueous cytokine concentration. Methods: In this cross-sectional study, aqueous humor samples were collected from 54 eyes of 54 patients (34 medically treated primary open angle glaucoma and 20 normal controls) during cataract surgery from January 2014 to January Glaucoma patients were divided into two groups: patients using prostaglandin analogue for more than 6 months (prostaglandin F 2α analogue [PGA] user) and patients with no experience of PGA use (PGA non-user). The levels of cytokines (matrix metalloproteinase [MMP]1, MMP9, MMP3, vascular endothelial growth factor, interleukin [IL]-1, IL-8, tumor necrosis factor [TNF]-α) in the aqueous of glaucoma and control subjects were quantified using a multiplex cytokine analysis. Results: Aqueous humor collected from the glaucoma patients exhibited significantly increased concentrations of MMP1 (p = 0.002) and MMP9 (p = 0.026). Among glaucoma patients, PGA users showed significantly higher level of MMP 9 compared with PGA non-users (p = 0.003). In the univariate and multivariate linear regression analyses, PGA use (β = 0.351, p = 0.027) and vertical cup-to disc ratio (β = , p = 0.013) were the significant risk factors associated with the level of MMP9. Conclusions: Primary open-angle glaucoma showed increased aqueous levels of MMP1 and MMP9. Especially, PGA use for longer than 6 months was associated with increased level of MMP9. J Korean Ophthalmol Soc 2016;57(4): Keywords: Aqueous humor, Cytokines, Glaucoma, Matrix metalloproteinase, Prostaglandin Received: Revised: Accepted: Address reprint requests to Jin A Choi, MD, PhD Department of Ophthalmology, The Catholic University of Korea St. Vincent's Hospital #93 Jungbu-daero, Paldal-gu, Suwon 16247, Korea Tel: , Fax: jinah616@hanmail.net * This research was supported by the Catholic Medical Center Research Foundation made in the program year of 2014 ( B ), 2015 ( B ) and the St. Vincent s Hospital, research institute of medical science (SVHR ). 녹내장은진행되는녹내장성시신경병증및이에상응하는시야결손으로정의되며안압상승이현재까지알려진가장중요한위험인자이다. 후방에서생성된방수 (aqueous humor) 는섬유주세포 (trabecular meshwork endothelial cell), 그리고쉴렘관을통하는섬유주쉴렘관경로를통하여대부분이배출되는데, 이러한배출로의저항이증가되었을때안압이상승된다. 1 개방각녹내장에서안압상승의원인인자로는변형된스테로이드대사, 아드레날린성조절장애, 비정상적면역학적과정, 산화로인한손상등의가능성이제기되고있지만, 방수배출로의저항증가에관계되는정확한원인에대해서는아직뚜렷이밝혀진것이없다. 1 c2016 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 601

2 - 대한안과학회지 2016 년제 57 권제 4 호 - 방수는적절한안압을유지하는기능외에안구내조직의생리적기능과대사적항상성을유지하는중요한기능을하며, 섬유주세포, 각막내피세포, 홍채, 수정체등과직접접촉하고있다. 따라서방수의특징을통하여간접적으로녹내장에있어섬유주세포등안압에관계되는전방조직의특징을밝히고자하는연구들이있어왔다. 2-5 녹내장안의방수에서염증성사이토카인이상승되어있음이보고된바있다. 4 또한섬유주세포에서생리적으로 extracellular matrix를분해시켜결과적으로 extracellular matrix의순환 (turnover) 에관여하는효소인 matrix metalloproteinase (MMP) 의농도가녹내장안에서증가되어있음이보고된바있다. 2,3,6 그러나실제녹내장환자의방수는녹내장자체뿐아니라, 환자의나이, 성별, 녹내장의정도, 그리고녹내장환자에서대부분평생유지해야하는안압하강제등에의해서도영향을받을가능성이많다. 그러나녹내장방수에서특징적으로발현되는사이토카인과녹내장환자의임상적특징의관계에대해서는많은보고가이루어지지않았다. 따라서본연구에서는녹내장안과정상안의방수를분석하여사이토카인의발현농도차이를알아보았다. 다음으로녹내장안에서어떠한임상적특징이방수사이토카인농도를결정하는지분석해보고자하였다. 대상과방법 본연구는비교분석적, 단면적연구로시행되었으며, 가톨릭대학교성빈센트병원의학윤리심의위원회 (IRB) 의승인을받았고 ( 승인번호 : VC14SISI0001) 헬싱키선언을따라시행되었다. 각환자에게연구시작전연구절차및과정에대한자세한설명과문서화된동의서를받은후연구를진행하였다. 2014년 1월부터 2015년 1월까지가톨릭대학교성빈센트병원안과에내원하여백내장수술을받은환자중방수수집에동의한개방각녹내장 ( 원발개방각녹내장및정상안압녹내장 ) 환자와정상안을대상으로하였다. 모든대상환자에게과거력을청취하였고, 최대교정시력검사, Goldmann 압평안압계를이용한안압검사, 굴절검사, 세극등현미경검사, 전방각검사, 안구길이, Pentacam R (Oculus, Wetzlar, Germany), 비접촉경면현미경을이용한각막내피세포검사가시행되었다. 이중녹내장환자들에게는안저촬영검사, Humphrey Visual Field Analyzer (Swedish Interactive Threshold Algorithm 24-2, Carl Zeiss Meditec, Dublin, CA, USA) 를이용한표준자동시야검사및 Stratus OCT (Carl Zeiss Meditec, Dublin, CA, USA) 를이용하여시신경단층촬영이시행되었다. 녹내장은시신경검사상, 수직시신경유두비의비대칭, 테얇아짐 (rim thinning), 패 임 (notching), 함몰 (excavation), 망막신경섬유층손상 (retinal nerve fiber layer defect) 등의녹내장성시신경변화를보이며시야검사에서이에상응하는녹내장성시야결손을보이는경우로정의하였다. 정상안은안압이 21 mmhg 이하이면서, 안저검사상정상시신경모습 ( 시신경유두테가정상이고, 시신경유두출혈, 시신경테얇아짐등이없음 ) 과망막신경섬유층결손이없는경우로정의하였다. 연구참여자는세극등현미경을이용한검사상정상적인전안부소견을보이고, 개방각을가진경우를대상으로하였으며, 검사결과에영향을미칠수있는백내장이외의안내질환 ( 망막정맥폐쇄, 망막동맥폐쇄, 당뇨망막병증, 연령관련황반변성등 ) 이나, 당뇨등의전신질환을가진경우를제외하였고, 이전의안내수술이나레이저치료를시행한경우, 안구내염증이있는경우, 면역저하제사용자등은대상에서제외하였다. 녹내장안은수술전사용하던약제의종류, 기간, 개수를기록하였고, 약제의종류에따라 prostaglandin F 2α analogue (PGA, Travoprost: Travatan, Alcon, Fort Worth, TX, USA; Latanoprost: Xalatan, Pfizer, New York, NY, USA; Bimatoprost: Lumigan, Allergan Inc., Irvine, CA, USA; Tafloprost: Taflotan, Santen Inc., Osaka, Japan) 를 6개월이상사용한군 (PGA 사용군 ) 과 PGA를사용하지않은군 (PGA 비사용군 ) 으로나누어분석하였다. 6개월이하로 PGA를사용했던환자는대상에서제외하였다. 4 모든연구참여자에게고식적인수정체유화술및인공수정체삽입술을시행하였다. 수술시행전에전방천자를통하여 100 μl의방수를수집하였다. 방수샘플은분석을위하여채취 2시간이내에 80 o C에서냉동보관되었다. Luminex multiplex bead immunoassay (Human Cytokine LINCOplex kit; LINCO Research, St. Charles, MO, USA) 를이용하여희석되지않은방수검체에존재하는 MMP1, MMP9, MMP3, Vascular endothelial growth factor (VEGF), interleukin (IL)-1, IL-8, Tumor necrosis factor (TNF)-α의농도를측정하였다. 시료의분석은제조회사의검사방침을준수하여이전연구에서보고된바와같은방법으로시행하였다. 7 녹내장안및정상대조군간, 그리고녹내장안중 PGA 사용군과 PGA 비사용군간의임상적특징및방수내사이토카인의농도에대한비교분석을시행하였다. 비교분석은연속변수에대해서는 independent t-test로, 범주형변수에대해서는 Pearson χ 2 을통하여검정하였다. 연속변수에대한결과는평균및표준편차로나타내었다. 다음으로방수내 MMP9의농도에미치는인자에대하여단변량선형회귀분석 (univariate linear regression analysis) 을시행하였 602

3 - 김효원외 : 녹내장방수의특징 - Table 1. Clinical characteristics of glaucoma patients and normal controls Glaucoma (n = 34) Normal Control (n = 20) p-value Age (years) 70.1 ± ± Sex (% of female) 27/50 23/ Laterality (% of right) 25/50 21/ Spherical equivalent (diopter) -1.4 ± ± Axial length (mm) 23.4 ± ± Vertical cup-to disc ratio 0.7 ± ± 0.1 <0.001 Preoperative IOP (mm Hg) 13.9 ± ± Postoperative 1 day IOP (mm Hg) 14.0 ± ± Postoperative 1 week IOP (mm Hg) 11.8 ± ± Values are presented as mean ± SD unless otherwise indicated. IOP = intraocular pressure. Figure 1. Comparisons of the aqueous concentrations of matrix metalloproteinase 1, 3, and 9 between glaucoma patients and normal controls. All the comparisons were performed by independent t-test. MMP = matrix metalloproteinase. 다. 단변량분석에서 p<0.2인인자를다변량분석에포함시켰으며, 후진제거법 (backward elimination process) 을이용하여최종다변량선형회귀분석을시행하였다. 통계학적분석은 SPSS statistical software 18.0 (SPSS Inc., Chicago, IL, USA) 을사용하였고, p-value가 0.05 미만인경우를통계학적으로유의한것으로정의하였다. 결과 개방각녹내장환자 34명의 34안, 정상안 20명의 20안이포함되었다. 녹내장안중 PGA 사용군은 21명 21안, PGA 비사용군은 13명 13안이었다. 녹내장안과정상대조군의평균나이는각 70.1 ± 11.7세, 64.4 ± 16.8세로두군간에통계적으로유의한차이가없었다 (p=0.026, Table 1). 그외두군간에성별, 우안의비율, 구면수치대응치, 안구길이역시두군간의유의한차이는없었다 (p=0.196, 0.246, 0.673, 0.216, Table 1). 수직시신경함몰비는녹내장안 0.7 ± 0.1, 정상대조군 0.4 ± 0.1로녹내장군에서유의하게컸다 (p<0.001). 방수의사이토카인분석결과, MMP1은녹내장군에서 6.4 ± 7.0 pg/ml, 대조군에서 1.8 ± 2.9 pg/ml (glaucoma vs. control, p=0.002), MMP3는녹내장군에서 ± pg/ml, 대조군에서 ± pg/ml (p=0.090), 그리고 MMP9은녹내장군에서 69.4 ± 67.4 pg/ml, 대조군에서 34.8 ± 41.2 pg/ml로 (p=0.026), 녹내장군에서 MMP1과 MMP9이대조군에비하여유의하게증가되어있는양상을보였다 (Fig. 1). 그외 VEGF는녹내장안에서 58.3 ± 40.6 pg/ml, 대조군에서 45.5 ± 33.5 pg/ml (p=0.285), IL-8은녹내장안에서 6.12 ± 2.9 pg/ml, 대조군에서 ± pg/ml (p=0.168), TNF-α는녹내장안에서 0.08 ± 0.22 pg/ml, 대조군에서 0.03 ± 0.09 pg/ml (p=0.347) 로두군간에유의한차이가없었으며, IL-1은두군모두에서검출되지않았다. 녹내장안을 PGA 사용군과 PGA 비사용군으로나누어분석했을때, PGA 사용군에서총녹내장약제수가유의하게많았으나 (p=0.029), 사용하는총녹내장약제중 PGA를제외한타약제를사용하는환자비율 (%) 은두군사이에유의한차이가없었다 (Table 2). 두군사이에방수사이토카인농도를분석하였을때 PGA 사용군에서 MMP9의농도가 ± pg/ml로 PGA 비사용군 ± pg/ml에비하여유의하게증가되어있는양상을보였다 (p=0.003, Table 2). 그외 MMP1, MMP3, IL-8, TNF-alpha 등의다른사이토카인은유의한차이를보이지않았다 (Table 2). 녹내장안에서방수의 MMP9 농도와관련된인 603

4 - 대한안과학회지 2016 년제 57 권제 4 호 - Table 2. Comparison of clinical characteristics and aqueous cytokine concentrations between glaucoma patients using prostaglandin analogues for longer than 6 months and patients with no experience of prostaglandin analogues PGA user (n = 21) PGA non-user (n = 13) p-value Clinical characteristics Age (years) 67.7 ± ± Average RNFL thickness (μm) 77.0 ± ± Axial length (mm) 23.3 ± ± Vertical cup-to disc ratio 0.73 ± ± Preoperative IOP (mm Hg) 13.8 ± ± Postoperative 1 day IOP (mm Hg) 12.5 ± ± Postoperative 1 week IOP (mm Hg) 12.5 ± ± Number of anti-glaucoma eyedrops (number) 1.5 ± ± Use of beta-blocker (%) Use of carbonid anhydrase inhibitor (%) Use of α-selective adrenergic drugs (%) Use of miotic agents (%) Duration of anti-glaucoma eyedrops (months) 18.2 ± ± Duration of PGA (months) 18.3 ± ± Aqueous cytokine concentration MMP1 (pg/ml) 6.7 ± ± MMP9 (pg/ml) 90.7 ± ± VEGF (pg/ml) 67.0 ± ± MMP3 (pg/ml) ± ± IL-1 (pg/ml) 0.0 ± ± 0.0 N/A IL-8 (pg/ml) 13.2 ± ± TNF-alpha (pg/ml) 0.0 ± ± Values are presented as mean ± SD unless otherwise indicated. PGA = prostaglandina analogues; RNFL = retinal nerve fiber layer; IOP = intraocular pressure; MMP = matrix metalloproteinase; VEGF = vascular endothelial growth factor; IL = interleukin; TNF = tumor necrosis factor; N/A = not applicable. Table 3. Clinical factors affecting aqueous concentration of MMP9 in glaucoma patients Parameters Univariate Multivariate B SE β p-value B SE β p-value Age Sex PGA user Axial length Preoperative IOP Average RNFL thickness Duration of PGA Number of anti-glaucoma eyedrops Vertical cup-to disc ratio MMP = matrix metalloproteinase; B = unstandardized coefficient; SE = spherical equivalent; β = standardized beta; PGA = prostaglandin analogue; IOP = intraocular pressure; RNFL = retinal nerve fiber layer. 자를선형회귀분석을통하여알아보았을때단변량및다변량분석모두에서 PGA 사용 (β=0.351, p=0.027), 낮은수직시신경함몰비 (β=-0.401, p=0.013) 가 MMP9 상승에영향을미치는독립적인인자였다 (Table 3). 고찰 정상적으로 Matrix metalloproteinase는섬유주세포에서분비되며, 섬유주세포사이에존재하는 extracellular matrix의 분해를촉진함으로써, extracellular matrix의순환 (turnover) 에핵심적인역할을하는효소이다. 8 녹내장환자의방수에서정상인과다른 MMP 농도를나타냄이이전연구에서보고된바있다. 2,6,9 Weinstein et al 3 은개의안구조직을조사한연구에서정상안에비해녹내장안의방수및전방각조직에서 MMP2와 MMP9의농도가증가해있다고하였다. 그러나 Pradhan et al 5 은실제환자의방수에서 MMP2와 MMP9을분석하였을때, 유의한차이가없었고, 사용하는프로스타글란딘제제 (prostaglandin F 2α analogue) 의종류에 604

5 - 김효원외 : 녹내장방수의특징 - 따라서도유의한차이가없다고하였다. 본연구에서는녹내장안의방수에 MMP1과 MMP9이증가되어있음을확인할수있었다 (Fig. 1). 본연구에서는녹내장안에서증가된 matrix metalloproteinase 가녹내장의병인에관계하는지, 아니면녹내장의치료에의한이차적인결과인지를확인하기위하여녹내장의임상적특징이 MMP의농도를결정하는지알아보고자하였다. 그결과 MMP9의경우프로스타글란딘제제를 6개월이상사용하였을때독립적으로 MMP9의상승과관련이있음을알수있었다 (β=0.351, p=0.027, Table 3). 여기서한가지흥미로운점은수직시신경함몰비의경우오히려작을수록, 즉녹내장의정도가덜심할수록 MMP9이상승되는방향으로나타났다는점이다 (β=-0.401, p=0.013). 이러한점에서미루어보았을때, MMP9은녹내장의직접적인병인또는질환의정도 (severity) 에관계한다기보다프로스타글란딘제제사용에의한이차적인결과일가능성이높다고보인다. 프로스타글란딘제제는특히포도막공막유출로 (uveoscleral outflow) 에영향을줌으로써안압을하강시키는가장강력한단일안압하강제중의하나이다. 10 프로스타글란딘제제는안방수의배출로뿐만아니라안구전반에걸쳐영향을미친다고보고되었다. 11 이전연구에서프로스타글란딘제제는섬모체근육세포 (ciliary smooth muscle cell) 12 및공막 13,14 에이르기까지전반적으로 MMP의농도를상승시킨다고하였고, 이로인하여조직의투과성이증가되어, 프로스타글란딘제제에의한안압하강의기전에일부관여한다고하였다. 13 이뿐아니라인간섬유주세포배양후, latanoprost로처리하였을때, 세포에서 MMP1, MMP3, MMP17 의발현이증가되었다. 15 또한최근에는프로스타글란딘제제를사용하는녹내장환자에서눈물의사이토카인농도를분석하였을때 MMP1, MMP9의증가와함께, 길항작용을하는 tissue inhibitor of metalloproteinase (TIMP)-1이감소되어있음이밝혀졌다. 16 방수의사이토카인은녹내장외의다른질환들의병인과도밀접한관계를가진다. Jia et al 17 은안축장의길이에따라서 MMP2, TIMP-1, 2, 3가증가한다고보고하였다. 또한당뇨망막병증에서 MMP2, MMP9이증가되어있고, 18,19 당뇨의신생혈관막에서 MMP9의증가가보고된바있다. 20,21 이로미루어볼때, 생리적인 MMP의조절메커니즘과는별도로, 프로스타글란딘제제의장기사용으로인하여 2차적으로 MMP1, 9의농도가증가하게되며, 이로인하여 MMP가안구에미칠수있는영향에대한고려도필요할것으로보인다. 프로스타글란딘은염증성반응의매개물질중하나로서 이론적으로프로스타글란딘제제의사용이안구의염증을유도할가능성이제시되어왔다. 22 MMP9 역시다양한염증반응을조절하는 pro-inflammatory mediator로알려져있다. 23 Chua et al 4 은정상안과녹내장안의방수를비교하여 interferon-gamma, IL-10 등의염증성사이토카인이개방각녹내장에서증가되어있다고보고하였다. 그러나본연구에서는 IL-1, IL-8, TNF-α 및 VEGF 등의염증성사이토카인들은녹내장군과정상군에서유의한차이가발견되지않았으며, 프로스타글란딘제제사용여부에따라서도유의한차이가발견되지않았다 (Table 2). 그러나본연구는백내장수술전에채취한방수에서분석한것으로, 다양한염증성사이토카인에대한분석은이루어지지못하였다. 당뇨나수술등과같이전방내염증이증가될것이예상되는스트레스상황에서 MMP9이전방내염증반응에미치는영향에대해서는추가연구가필요할것으로보인다. 24,25 본연구는전향적연구로직접사람의방수를대상으로분석했다는장점이있다. 본연구에서는다변량분석을통하여프로스타글란딘제제사용외에방수내 MMP 농도에영향을줄수있는다른인자를보정하여분석하였으나, 대상안수의부족으로인하여프로스타글란딘단일제제만을사용한환자에대한분석이별도로시행되지못했다는점이연구의제한점으로사료된다. 결론적으로, 녹내장환자의방수를분석하였을때, MMP1, MMP9이상승되어있었고, 특히 6개월이상의프로스타글란딘제제의사용은 MMP9의상승과관련된위험인자임을알수있었다. REFERENCES 1) Tamm ER. The trabecular meshwork outflow pathways: structural and functional aspects. Exp Eye Res 2009;88: ) Markiewicz L, Pytel D, Mucha B, et al. Altered expression levels of MMP1, MMP9, MMP12, TIMP1, and IL-1β as a risk factor for the elevated IOP and optic nerve head damage in the primary open-angle glaucoma patients. Biomed Res Int 2015;2015: ) Weinstein WL, Dietrich UM, Sapienza JS, et al. Identification of ocular matrix metalloproteinases present within the aqueous humor and iridocorneal drainage angle tissue of normal and glaucomatous canine eyes. Vet Ophthalmol 2007;10 Suppl 1: ) Chua J, Vania M, Cheung CM, et al. Expression profile of inflammatory cytokines in aqueous from glaucomatous eyes. Mol Vis 2012;18: ) Pradhan ZS, Dalvi RA, Lai T, et al. Prostaglandin agonist effect on matrix metalloproteinase aqueous levels in glaucoma patients. Can J Ophthalmol 2015;50: ) Chintala SK, Wang N, Diskin S, et al. Matrix metalloproteinase gelatinase B (MMP-9) is associated with leaking glaucoma filtering blebs. Exp Eye Res 2005;81: ) dupont NC, Wang K, Wadhwa PD, et al. Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: de- 605

6 - 대한안과학회지 2016 년제 57 권제 4 호 - terminations of a panel of nine cytokines in clinical sample culture supernatants. J Reprod Immunol 2005;66: ) Alexander JP, Samples JR, Van Buskirk EM, Acott TS. Expression of matrix metalloproteinases and inhibitor by human trabecular meshwork. Invest Ophthalmol Vis Sci 1991;32: ) De Groef L, Van Hove I, Dekeyster E, et al. MMPs in the neuroretina and optic nerve: modulators of glaucoma pathogenesis and repair? Invest Ophthalmol Vis Sci 2014;55: ) Nakakura S, Tabuchi H, Baba Y, et al. Comparison of the latanoprost 0.005%/timolol 0.5% + brinzolamide 1% versus dorzolamide 1%/timolol 0.5% + latanoprost 0.005%: a 12-week, randomized open-label trial. Clin Ophthalmol 2012;6: ) Toris CB, Gabelt BT, Kaufman PL. Update on the mechanism of action of topical prostaglandins for intraocular pressure reduction. Surv Ophthalmol 2008;53 Suppl1:S ) Weinreb RN, Kashiwagi K, Kashiwagi F, et al. Prostaglandins increase matrix metalloproteinase release from human ciliary smooth muscle cells. Invest Ophthalmol Vis Sci 1997;38: ) Weinreb RN, Lindsey JD, Marchenko G, et al. Prostaglandin FP agonists alter metalloproteinase gene expression in sclera. Invest Ophthalmol Vis Sci 2004;45: ) Kim JW, Lindsey JD, Wang N, Weinreb RN. Increased human scleral permeability with prostaglandin exposure. Invest Ophthalmol Vis Sci 2001;42: ) Oh DJ, Martin JL, Williams AJ, et al. Effect of latanoprost on the expression of matrix metalloproteinases and their tissue inhibitors in human trabecular meshwork cells. Invest Ophthalmol Vis Sci 2006;47: ) Lopilly Park HY, Kim JH, Lee KM, Park CK. Effect of prostaglandin analogues on tear proteomics and expression of cytokines and matrix metalloproteinases in the conjunctiva and cornea. Exp Eye Res 2012;94: ) Jia Y, Hu DN, Zhu D, et al. MMP-2, MMP-3, TIMP-1, TIMP-2, and TIMP-3 protein levels in human aqueous humor: relationship with axial length. Invest Ophthalmol Vis Sci 2014;55: ) Mohammad G, Kowluru RA. Novel role of mitochondrial matrix metalloproteinase-2 in the development of diabetic retinopathy. Invest Ophthalmol Vis Sci 2011;52: ) Mohammad G, Kowluru RA. Matrix metalloproteinase-2 in the development of diabetic retinopathy and mitochondrial dysfunction. Lab Invest 2010;90: ) Hoffmann S, He S, Ehren M, et al. MMP-2 and MMP-9 secretion by rpe is stimulated by angiogenic molecules found in choroidal neovascular membranes. Retina 2006;26: ) Das A, McGuire PG, Eriqat C, et al. Human diabetic neovascular membranes contain high levels of urokinase and metalloproteinase enzymes. Invest Ophthalmol Vis Sci 1999;40: ) Hu J, Van den Steen PE, Sang QX, Opdenakker G. Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat Rev Drug Discov 2007;6: ) Kawasaki Y, Xu ZZ, Wang X, et al. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat Med 2008;14: ) Song YJ, Jung JH, Kim DG. Analysis of aqueous humor cytokines in diabetic retinopathy. J Korean Ophthalmol Soc 2014;55: ) Sin BH, Kim JY, Park JY, Park SP. Analysis of intraocular cytokines according to progression of diabetic retinopathy and macular edema in diabetic patients. J Korean Ophthalmol Soc 2013;54: = 국문초록 = 녹내장환자의방수내사이토카인농도분석 목적 : 녹내장안과정상안의방수에서사이토카인의농도차이를알아보고, 녹내장안에서어떠한임상적특징이방수내사이토카인농도를결정하는지분석해보고자하였다. 대상과방법 : 2014 년 1 월부터 2015 년 1 월까지백내장수술을받은환자중개방각녹내장 ( 원발개방각녹내장및정상안압녹내장 ) 환자와정상안을대상으로하였다. 녹내장안은점안프로스타글란딘제제 (prostaglandin F 2α analogue, PGA) 를 6 개월이상사용한군 (PGA 사용군 ) 과 PGA 를사용하지않은군 (PGA 비사용군 ) 으로나누어분석하였다. 결과 : 녹내장환자 34 명의 34 안, 정상인 20 명의 20 안이포함되었고녹내장안중 PGA 사용군은 21 안, PGA 비사용군은 13 안이었다. 방수의사이토카인분석결과, 녹내장안에서 MMP1 과 MMP9 이정상대조군에비해유의하게증가된양상을보였다 (p=0.002 and 0.026, MMP1 and MMP9). 녹내장안중에서는 PGA 사용군에서 MMP9 이 ± pg/ml 로 PGA 비사용군 ± pg/ml 에비하여유의하게증가되어있었다 (p=0.003). 단변량및다변량분석모두에서 PGA 사용여부 (β=0.351, p=0.027) 및낮은수직시신경함몰비 (β=-0.401, p=0.013) 가 MMP9 상승에유의한영향을미쳤다. 결론 : 녹내장환자의방수를분석하였을때, MMP1 과 MMP9 이상승되어있었고, 특히 6 개월이상프로스타글란딘제제의사용은 MMP9 의상승에영향을미치는인자임을알수있었다. < 대한안과학회지 2016;57(4): > 606

012임수진

012임수진 Received : 2012. 11. 27 Reviewed : 2012. 12. 10 Accepted : 2012. 12. 12 A Clinical Study on Effect of Electro-acupuncture Treatment for Low Back Pain and Radicular Pain in Patients Diagnosed with Lumbar