Telaah Telaah Ilmiah
Ekspresi VEGF Pada Retinopati Diabetik
Oleh
Dodi Maulana, S.Ked
Pembimbing
dr. Ramzi Amin, Sp.M (K)
DEPARTEMEN ILM !E"E#ATAN MATA R"P DR$ MO#AMMAD #OE"IN PALEM%ANG FA!LTA" !EDO!TERAN NIVER"ITA" "RI&I'A(A )*+,
#ALAMAN PENGE"A#AN 1
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'-d-l Telaah Ilmiah
Ekspresi VEG !ada Re"inopa"i Dia#e"ik
Oleh.
Dodi Maulana, S.Ked $%$&%'&*$+
Ree Reera ra"" ini ini diadia-uk ukan an un"u un"uk k memen emenuh uhii sala salah h sa"u sa"u "ua "uass dala dalam m men menik iku" u"ii Kepa Kepani ni"e "era raan an Klin Klinik ik Seni Senior or di /ai /aian an Ilmu Ilmu Kese Keseha ha"a "an n Ma"a Ma"a RS0! RS0! Dr. Dr. Mohamm Mohammad ad 1oesin 1oesin !alem# !alem#an an akul" akul"as as Kedok" Kedok"eran eran 0ni2er 0ni2ersi"a si"ass Sri3iSri3i-a4a a4a periode 5$ 6anuari $* s.d & e#ruari $*
!alem#an,
e#ruari $*
dr. Ramzi Amin, Sp.M (K)
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!ATA PENGANTAR !u-i dan s4ukur penulis ha"urkan kepada Tuhan 7ME karena a"as rahma" dan #erka"894a Telaah Ilmiah 4an #er-udul :Ekspresi VEG !ada Re"inopa"i Dia#e" Dia#e"ik; ik; ini dapa" dapa" diselesa diselesaika ikan n "epa" "epa" 3ak"u. 3ak"u. Telaah elaah Ilmiah Ilmiah ini di#ua" di#ua" un"uk un"uk memenu memenuhi hi salah salah sa"u sa"u s4ara" s4ara" u-ian u-ian kepani" kepani"era eraan an klinik klinik senior senior di /aian /aian Ilmu Ilmu Keseha"an Ma"a RS0! Dr. Mohammad 1oesin !alem#anakul"as Kedok"eran 0ni2ersi"as Sri3i-a4a. !enuli !enuliss -ua -ua inin inin men4am men4ampai paikan kan "erima "erima kasih kasih kepadadr kepadadr.. Ramzi Ramzi Amin, Amin, Sp.M (K) a"as #im#inann4a sehina penulisan ini men-adi le#ih #aik. !enu !enuli liss men4 men4ada adari ri masih masih #an4 #an4ak ak keku kekuran rana an n dan dan keke kekeli lirua ruan n dalam dalam penulisan "elaah Ilmiah ini.
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DAFTAR I"I #ALAMAN 'DL $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$ii #ALAMAN PENGE"A#AN $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ii $$$$$$$$$ii !ATA !ATA PENGANTAR PENGANTAR $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$iii $$$$$$$$$$$$$$$$$$$$$$$$iii DAFTAR DAFTAR I"I $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$i/ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$i/ DAFTAR DAFTAR GAM%AR$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ GAM%AR$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ / DAFTAR DAFTAR TA%EL$$$$$$$$$$$$$$$$$$ TA%EL$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ /i %A% I PENDA#LAN$$$$$$$$$$$$$$$$$$$$$$$$$$$ PENDA#LAN$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$+ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$+ %A% II TIN'AAN P"TA!A P"TA!A $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$) )
. Dia#e"es Meli"us.......................................... Meli"us................................................................. ................................................. .......................... . Re"inopa"i Dia#e"ik............................................ Dia#e"ik.................................................................................... ........................................ .. .5 !eranan !eranan VEG pada Re"inopa"i Re"inopa"i Dia#e"ik....... Dia#e"ik............ .......... .......... .......... ......... ......... .......... .......... ..........= .....= .% VEG Se#aai Tare" Tare" Terapi..................... Terapi............................................. .................................................+ .........................+ %A% III !E"IMPLAN$$$$$$$$$$$$$$$$$$$$$$$$$ !E"IMPLAN$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$+0 $$$$$$$$$$$$$$+0 DAFTAR DAFTAR P"TA!A$$$$$$$$$$$$$$$$$$$ P"TA!A$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$ $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$+1 $$$$$$$$$$$$$$$$$$$$$$$$$$$+1
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%A% I PENDA#LAN
Re"inopa"i Re"inopa"i dia#e"ik merupakan merupakan salah sa"u pen4e#a# #erkurann4 #erkurann4aa "a-am peneliha"an pada penderi"a dia#e"es meli"us (DM). DM adalah sua"u kelompok pen4aki" me"a#olik denan karak"eris"ik hiperlikemia 4an "er-adi karena kelainan sekresi insulin ("ipe ), ker-a insulin ("ipe ), a"au kedua8duan4a. !asien dia#e" dia#e"es es memili memiliki ki risiko risiko & kali kali le#ih le#ih mudah mudah menal menalami ami ke#u"aa ke#u"aan n di#and di#andin in nondia#e"es. Se"iap "ahun "er-adi peninka"an insidensi DM di seluruh dunia. Re"inopa"i dia#e"ik adalah salah sa"u komplikasi mikroaniopa"i kronik dari dia#e"es, dia#e"es, di"andai di"andai denan denan adan4a adan4a kerusakan kerusakan dan sum#a"an pada pem#uluh pem#uluh darah kapiler re"ina. Re"inopa"i dia#e"ik meninka" se-alan denan laman4a dia#e"es. !ada !ada re"i re"ino nopa pa"i "i dia# dia#e" e"ik ik
VEG VEG (vascu (vascular lar endoth endotheli elial al grow growth th factor factor
memi memili liki ki pera perana nan n 4an 4an #esa #esarr "erh "erhad adap ap perk perkem em#a #an nan an prol prolie iera ra"i "i dia# dia#e"i e"ik k re"inop re"inopa"i a"i dan dia#e"i dia#e"ik k makula makularr edema. edema. VEG VEG merupa merupakan kan #aian #aian dari dari growth fartors fartors 4an #erunsi un"uk memi>u 2askuloenesis dan anioenesis. VEG disekresikan "eru"ama dari epi"el pimen re"ina sel, peri>4"es, as"rosi", sel M?ller, sel lial, dan sel endo"el. Sekresi VEG "eru"ama dipi>u oleh keadaan hipoksia a"au iskemia -arinan pada re"ina re"i na 4an diaki#a"kan oleh komplikasi mikro2askular pada penderi"a DM. !eno# !eno#a"a a"an n re"inop re"inopa"i a"i dia#e" dia#e"ik ik melipu melipu"i "i penen penendali dalian an lukos lukosaa darah, darah, "ekana "ekanan n darah, darah, s"eroid s"eroid in"ra2 in"ra2i"r i"reus, eus, ser"a ser"a o"oko o"okoau aulasi lasi laser. laser. /aru8# /aru8#aru aru ini #erkem#an penunaan an"i VEG (vascular (vascular endothelial endothelial growth growth factor) pada "erapi re"inopa"i dia#e"ik se"elah an"i VEG dipu#likasi mem#eri hasil 4an #aik pada ARMD (age-related macular degeneration). !eno#a"an menunakan an"i VEG VEG dinilai dinilai le#ih le#ih aman aman dan melilik melilikii sediki sediki"" kompli komplikas kasii di#and di#andin in denan denan peno#a"an laser.
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%A% II TIN'AAN P"TA!A
)$+$ )$+$ Diabet Diabetes es melitmelit-ss 2DM3 2DM3
Dia#e"es Meli"us merupakan sua"u kelompok pen4aki" me"a#olik denan karak"eris"ik karak"eris"ik hiperlikemia hiperlikemia 4an "er-adi karena kelainan kelainan sekresi insulin, ker-a insulin, insulin, a"au kedua8duan4 kedua8duan4a. a. 1iperlikem 1iperlikemia ia kronik kronik pada dia#e"es dia#e"es #erhu#un #erhu#unan an denan kerusakan -anka pan-an, disunsi a"au keaalan #e#erapa oran "u#uh, "eru"ama ma"a, in-al, sara, -an"un dan pem#uluh darah. Se>ara epidemioloi epidemioloi "er-adi peninka peninka"an "an -umlah kasus dia#e"es dia#e"es di seluruh dunia. dunia. !en4aki" !en4aki" ini serinkali serinkali "idak "erde"eksi, "erde"eksi, dan dika"akan dika"akan onse" a"au mulai "er-adin4a dia#e"es adalah * "ahun se#elum dianosis di"eakkan. DM 4an "idak dikelola denan #aik, dia#e"es meli"us akan men4e#a#kan "er"er-ad adin in4 4a
#er# #er#a aai ai
komp kompli lika kasi si
kron kronik ik,,
#aik #aik
mikr mikroa oan nio iopa pa"i "i
maupu aupun n
makroan makroanio iopa" pa"i. i. !eru#a !eru#ahan han@dis @disun unsi si dasar dasar pada pada DM "eru"am "eru"amaa "er-adi "er-adi pada pada endo endo"el "el pem# pem#ul uluh uh darah darah,, sel o"o" o"o" polo poloss pem# pem#ul uluh uh dara darah h maup maupun un pada pada sel mesanial in-al. !a"oloi dimulai dari keadaan hiperlisolia, 4ai"u sua"u keadaan dima dimana na
sel sel
ke#a ke#ann-ir iran an
masu masukn kn4 4a
luk lukos osaa
aki# aki#a" a"
hipe hiper rli like kemi miaa
kron kronik ik..
1iperliso 1iperlisolia lia akan menu#ah homeos"asis homeos"asis #iokimia3i #iokimia3i sel melalui #e#erapa -alur #iokimia3i seper"i -alur aldosa reduk"ase, s"res s"re s oksida"i si"oplasmik, si "oplasmik, -alur pro"ein kina kinase se dan dan "er#e "er#en" n"uk ukn4 n4aa spesi spesies es lik likos osila ilasi si lanlan-u" u" in"ra in"rasel sel.. Sala Salah h sa"u sa"u komplikasi mikroaniopa"i dari DM 4ai"u re"inopa"i dia#e"ik. 5
)$)$
Retinopati diabetik 2RD3
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Re"inopa"i Re"inopa"i dia#e"ik dia#e"ik adalah sua"u mikroanio mikroaniopa"i pa"i proresi proresi 4an di"andai oleh oleh keru kerusak sakan an dan dan sum# sum#a"a a"an n pem# pem#ul uluh uh8p 8pum um#u #ulu luh h halu halus, s, melipu melipu"i "i ar"erio ar"erioll prekapiler re"ina, kapiler8kapiler dan 2ena82ena.% Re"inopa"i dia#e"ik merupakan pen4e#a# ke#u"aan palin serin di"emukan pada usia de3asa an"ara $8*% "ahun di neara ma-u. Di Amerika "erdapa" &$$$ ke#u"aan ke#u"aan aki#a" re"inopa"i re"inopa"i dia#e"ik. !asien dia#e"es memiliki memiliki risiko & kali le#ih mudah menalami ke#u"aan di#andin nondia#e"es. Risiko menalami re"inopa"i pada pasien dia#e"es meninka" se-alan denan laman4a dia#e"es. !ada 3ak"u dian dianosis osis DM "ipe "ipe di"ea di"eakka kkan, n, RD han4a han4a di"emu di"emukan kan pada kuran kuran dari &B pasien. Se"elah $ "ahun, pre2alensi meninka" men-adi %$8&$B dan sesudah $ "ahu "ahun n le#ih le#ih dari dari +$B +$B pasie pasien n suda sudah h mend menderi eri"a "a RD. RD. !ada !ada DM "ipe "ipe ke"i ke"ika ka dian dianosis osis DM di"eak di"eakkan kan,, seki"ar seki"ar &B sudah sudah menderi menderi"a "a RD nonpro nonproli liera" era"i. i. Se"el Se"elah ah $ "ahun "ahun,, pre2 pre2al alen ensi si RD meni menin nka ka"" menmen-ad adii le#i le#ih h dari dari =$B =$B dalam dalam #er#aai dera-a".&,= Kelaian dasar dari re"inopa"i dia#e"ik "erle"ak pada kapiler re"ina 4an "erdiri dari 5 lapisan dari luar ke dalam 4ai"u sel perisi", mem#rana #asalis, dan sel endo endo"el "el.. Sel Sel peri perisi" si" #eru #erun nsi si memp memper er"ah "ahan anka kan n s"ruk s"ruk"u "urr kapi kapiler ler,, men mena"u a"ur r kon"rak kon"rak"ili "ili"as "as,, memper memper"ah "ahank ankan an unsi unsi #arier #arier dan "ranspo "ranspor"a r"asi si kapiler kapiler,, ser"a ser"a menendalikan prolierasi endo"el. Dalam kedaan normal per#andinan sel perisi" denan endo"el kapiler re"ina adalah C. Mem#rana #asalis #erunsi se#aai #arier denan memper"ahankan permea#ili"as kapiler aar "idak "er-adi ke#o>oran. !eru#ahan his"opa"olois kapiler re"ina pada RD dimulai dari pene#alan mem#ran
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Gambar +$ Sel !erisi" pada kapiler.*
Ke#u Ke#u"a "aan an aki# aki#a" a" re"in re"inop opa"i a"i dia# dia#e"i e"ik k dapa dapa"" "er-a "er-adi di melal melalui ui #e#e #e#era rapa pa mekanisme #eriku"C ) Edema makula a"au nonperusi kapiler, ) !em#en"ukan pem#uluh darah #aru pada RD proliera"i dan kon"raksi -arinan i#rosis men4 men4e# e#a# a#ka kan n
a#la a#lasi sio o
re"i re"ina na,,
5) !em# !em#ul uluh uh dara darah h
#aru #aru 4an 4an "er# "er#en en"u "uk k
menim#ulkan perdarahan prere"ina dan 2i"ereus, %) !em#en"ukan pem#uluh darah #aru dapa" menim#ulkan laukoma. = Dianosis re"inopa"i dia#e"ik didasarkan a"as hasil pemeriksaan unduskopi. !emeriksaan fundal !emeriksaan fundal fluorescein angiography (A) merupakan me"ode dianosis 4an palin dier>a4a. 9amun dalam klinik, pemeriksaan denan o"almoskopi masih dapa" diunakan un"uk skrinin. = Early Treatment Treatment Diabetic Retinopathy Study Reasearch roup roup (ETDRS) mem#ai re"inopa"i dia#e"ik a"as nonproliera"i dan proliera"i. !er"emuan !irlie !er"emuan !irlie "ouse mem#ai mem#ai RD a"as 5 s"adium 4ai"u s"adium nonproliera"i, nonproliera"i, preproliera"i, preproliera"i,
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Gambar )$ unduskopi pada Re"inopa"i Dia#e"ik. '
)$)$+$
Retinopati diabetik diabetik nonproli4erat nonproli4erati4 i4 2NPDR3
Re"inopa"i dia#e"ik nonproliera"i (9!DR 3 merupakan #en"uk 4an palin rinan dan serin "idak memperliha"kan e-ala. S"adium ini suli" dide"eksi dide"eksi han4a denan pemeriksaan pemeriksaan o"almoskop o"almoskopii lansun lansun maupun maupun "idak lansun. ara 4an palin #aik adalah denan menunakan o"o undus dan A. Mikroaneurisma 4an "er-adi pada kapiler re"ina merupakan "anda palin a3al 4an dapa" diliha" pada 9!DR. Mikroaneurisma didua #erhu#unan denan ak"or 2asoproliera"i 4an dihasilkan endo"el, kele kelem mahan ahan
dind dindin in
kapi kapile lerr
aki# aki#a" a"
#erk #erkur uran ann n4 4a
sel sel
peri perisi si", ",
ser" ser"aa
meninka"n4a "ekanan in"raluminal kapiler. Kelainan moroloi lain ialah pene#alan mem#rana #asalis, perdarahan rinan, eksuda" keras 4an "ampak se#aai #er>ak #er3arna kunin dan eksuda" lunak 4an "ampak se#aai
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Dalam Dalam 3ak"u 3ak"u 85 "ahun, "ahun, 9!DR 9!DR #era" #era" serin serin #erkem #erkem#an #an men-adi men-adi RD proliera"i.= )$)$)$
Retinopati diabetik proli4erati4 2PDR3
Re"inopa"i dia#e"ik proliera"i (!DR) di"andai denan pem#en"ukan pem#uluh darah #aru, 4an han4a "erdiri dari sa"u lapisan lapis an sel s el endo"el "anpa sel perisi" dan mem#rana mem#rana #asalis sehina #ersia" sana" rapuh dan mudah menalami menalami perdarahan. perdarahan. !em#uluh darah #aru "erse#u" sana" #er#aha4a karena "um#uh se>ara a#normal keluar dari re"ina meluas sampai ke 2i"reus, men4e# men4e#a#k a#kan an perdar perdaraha ahan n dan dapa" dapa" menim# menim#ulk ulkan an ke#u"a ke#u"aan. an. Apa#i Apa#ila la perdarahan "erus #erulan, dapa" "er-adi -arinan -ar inan i#rosis a"au sika"rik pada re"ina. re"ina. Sika"ri Sika"riks ks dan -arina -arinan n i#ros i#rosis is 4an 4an "er-ad "er-adii dapa" dapa" menari menarik k re"ina re"ina sampai "erlepas sehina sehina "er-adi a#lasio re"ina. !em#uluh !em#uluh darah #aru dapa" -ua "er#en"uk di dalam s"roma dari iris dan #ersama denan -arinan i#r i#ros osis is 4an 4an "er-a "er-adi di dapa dapa"" melua meluass sampa sampaii ke sudu sudu"" dari dari kamera kamera okul okulii an"erior sehina men4e#a#kan alukoma neo2askular.= )$)$0$
Mak-lopati diabetik
Makulopa"i dia#e"ik merupakan pen4e#a# ke#u"aan palin serin pada re"inopa"i dia#e"ik. Makulopa"i re"inopa"ik >enderun #erhu#unan denan DM "ipe "ipe usia usia lanlan-u" u",, sedan sedank kan an re"i re"ino nopa" pa"ii prol prolie iera" ra"i i >end >enderu erun n di"e di"emu muka kan n pada pada usia usia muda muda.. Makul Makulop opa" a"ii dia# dia#e" e"ik ik di#e di#edak dakan an menmen-ad adii makulopa"i iskemik, makulopa"i eksuda"i, dan edema makula. Makulopa"i iskemik "er-adi aki#a" pen4um#a"an 4an luas dari kapiler di daerah sen"ral
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$ascular Endothelial rowth %actors (VEG) %actors (VEG) adalah #aian daari rowth %actors 4an 4an #erun #erunsi si se#aai se#aai sin4al sin4al pro"ei pro"ein n un"uk un"uk kedua kedua 2as>ul 2as>uloe oenes nesis is (pem#en"ukan de no2o dari sis"em peredaran darah em#rio) dan anioenesis (per"u (per"um#u m#uhan han pem#ul pem#uluh uh darah darah dari dari pem#ul pem#uluh uh darah darah 4an 4an sudah sudah ada). ada). VEG VEG disekresikan "eru"ama dari epi"el pimen re"ina sel, peri>4"es, as"rosi", sel M?ller, sel lial, dan sel8sel endo"el. VEG memiliki #e#erapa ano"a "ermasuk VEG8 A, VEG8/, VEG8/, VEG8, VEG8, VEG8D VEG8D dan placental growth factors (!G). (!G). Sekresi Sekresi VEG "eru"ama dipi>u oleh keadaan hipoksia a"au iskemia -arinan pada re"ina 4an diaki#a"kan oleh mikroaniopa"i pada penderi"a DM. Semua ano"a VEG meransan respon seluler denan menika" resep"or kinase "irosin pada permukaan sel endo"el, 4an men-adikan molekul8molekul VEG #erdimerisasi dan men-adi ak"i melalui -alur "ransosorilasi. VEG8A memili memiliki ki dua -enis resep"orC resep"orC VEG resep"o resep"orr (VEGR (VEGR8 8 a"au l"8) l"8) dan (VEGR8 a"au KDR). !ada manusia, VEGR8 adalah pro"ein 4an dikodekan oleh en l"8 dan VEGR8 adalah &inase insert Domain Receptors (KDR, "ipe III
resep"or
"irosin
kinase)
4an
dikodekan
oleh
en
KDR.
VEGR8 "ampakn4a men-adi resep"or u"ama 4an #erperan dalam hampir semua respon seluler un"uk VEG8A. Resep"or VEG memiliki "ia #aianC #aian 4an eks"ras eks"raselu eluler ler "erdiri "erdiri dari dari "u-uh "u-uh domain domain 4an 4an men4eru men4erupai pai imuno imunolo# lo#uli ulin, n, sa"u ren"an "ransmem#ran "unal 4an #ersia" hidroo#ik, dan #aian in"raseluler menandun se#uah pe>ahan domain "4rosine kinase. + Ke"ika molekul VEG men menik ika" a"
#ai #aian an
e#a# e#a#ka ka
eks" eks"ra rase selu lule lerr
os os il i
sidu sidu
dari dari
rese resep" p"or or in
VEG VEG,,
#ai #aian an
in"r in"ras asel elul uler er
"i si
da
al
si
lule lule
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Indukksi
VEG
man anak"ika kan
mitogen-acti mitogen-activated vated
protein protein
(MA! (MA!), ),
4an an
menaki#a"kan prolierasi sel endo"el. kaskade ini #er"epa"an denan ak"i2asi -alur phopha"id4linosi"ol 58kinase (!I5) @ Ak" se"elah induksi VEGR8. VEG8A meransan sel8sel endo"el un"uk melepaskan ma"riks me"alopro"einase (MM!) dan uroinase uroinase-type -type plasminoge plasminogen n activator activator , 4an 4an men menak aki# i#a"k a"kan an der derad adasi asi mem#ran #asemen" dan mem#ua" mirasi sel memunkinkan. Sel endo"el 4an diak"ikan menhasilkan in"erin seper"i 25 dan 2&, 4an mem#an"u dalam mirasi melalui ma"riks 4an "erderadasi. !rolierasi dan mirasi sel endo"el 4an diiku"i oleh sin"esis mem#ran #asemen" un"uk mem#en"uk kapiler #aru. S"a#ili"as kapiler ini di>apai denan perekru"an peri>4"es dan sel8sel o"o" polos 4an dia"ur oleh platelet-derived oleh platelet-derived growth factor (!DG). (!DG).
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Hipoksia (Saturasi Oksigen <5% HIF-1 (hpo!ia in"u#e" $a#tor a &' in"ing protein )ranskripsi )ranskripsi gen *+,F *Bevasirnab transkripsi *+,F ./&' protein O/ 15 "ari .entrans$er *+,F "ari retikuu. retikuu. en"opas.a ke ke a"an gogi
*+,F "ikeuarkan *Ranibizumab, bavacizumab, macugen 0igan" erikatak "engan reseptor tirosine kinase pa"a se en"ote *Afbercept (decay receptor) 3 aur $os$oriasi
I3 hosphati"inosito 3 kinase /as .e.rane asso#iate" .e.rane asso#iate" guanine nu#eoti"e i I2 hosphati"insito-45 iphosphat
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)$1$
VEGF "ebagai "ebag ai Target Target Te Terapi rapi
/an4ak /an4ak peneli" peneli"ian ian 4an 4an "elah "elah dilaku dilakukan kan un"uk un"uk mempela mempela-ari -ari mekani mekanisme sme VEG denan harapan harapan menurani menurani neo2askularisasi neo2askularisasi dan ke#o>oran ke#o>oran pem#uluh pem#uluh darah ser"a eek dari VEG. !ada am#ar 5 di"un-ukan lokasi o#a" #eker-a dari o#a" 4an menare"kan neo2askularisasi a#normal. !roduksi VEG di#u"uhkan pada #an4ak proses isiolois normal seper"i pada keadaan perkem#anan em#rionik, pem#en"ukan pem#uluh darah #aru pada -arinan 4an menalami "rauma ("ermasuk pen4em#uhan luka), dan kola"eral pada pem#uluh darah 4an "ersum#a". VEG -ua dihasilkan pada proses pa"olois, an"ara lain pada per"um#uhan pem#uluh darah "umor dan per"um#uhan pem#uluh darah #aru pada pen4aki" re"ina 4an -ua dikenal denan wet macular degeneration. degeneration. Terapi rapi an"i an"i8VE 8VEG G di"u di"u-uk -ukan an un"u un"uk k men> men>e eah ah pem# pem#en" en"uk ukan an pem#uluh darah #aru pada kasus "erse#u" denan mem#lok aksi VEG. VEG. Se-arah a3al penunaan an"i8VEG #era3al dari "eori 6udah olkman, seoran ahli #edah anak 1ar2ard. Dia #erpendapa" anioenesis #erperan pen"in pada per"um#uhan "umor, dan #erhipo"esis penhen"ian anioenesis dapa"
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paruh + hari. !ro"okol rani#izuma# 4an direkomendasikan 4ai"u $,& m@$,$& mF diin-eksikan se>ara in"ra2i"real denan prosedur s"eril sa"u kali se"iap #ulan (% minu) selama 58= #ulan. Ineksi okular@periokular dan hipersensi"i2i"as adalah kon"raindikasi pem#erian o#a" ini. 8% /e2a>iz /e2a>izuma uma# # adalah full-length an"i#o an"i#odi di an"i an"i VEG8 VEG8A A 4an 4an pada pada a3aln4a diormulasikan un"uk "erapi kanker kolon denan pem#erian se>ara in"ra2 in"ra2ena ena.. /e2a>iz /e2a>izuma uma# # memilik memilikii rumus rumus s"ruk"u s"ruk"urr 6==5'#$=$N*$O$'"%% den denan an #era #era"" molek molekul ul %+ %+ kDa kDa dan dan masa masa paru paruh h le#ih le#ih kura kuran n $ hari hari.. !ro" !ro"ok okol ol #e2a #e2a>iz >izum uma# a# pada pada o"al o"almo molo loi i 4ai"u 4ai"u ,& ,& m diin diin-ek -eksik sikan an in"ra2i"real denan prosedur s"eril kali se"iap #ulan (% minu) selama 5 #ulan per"ama. !eno#a"an lan-u"an dapa" di#erikan #ila "er-adi penurunan ke"a-am ke"a-aman an peneli peneliha" ha"an an dan a"au a"au edema edema makula makula kem#ali kem#ali se"elah se"elah "erapi. "erapi. 5,%,&,
!er# !er#an andi din nan an eek eek"i2 "i2i"a i"ass
rani rani#i #izu zuma ma# #
dan dan #e2a #e2a>iz >izum uma# a# masi masih h
men-ad men-adii perde# perde#a"an a"an para para ahli. ahli. 9amun 9amun karena karena per#an per#andin dinan an #ia4a, #ia4a, le#ih le#ih #an4ak klinisi menunakan #e2a>izuma# #e2a>izuma# di#andin rani#izuma#. 5,%
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ke"e#alan makula an"ara minu ' dan . Selain i"u, dosis 4an le#ih "ini menhasilkan penuranan #esar dalam ke"e#alan dari dosis "erendah . = )$1$0$ )$1$0$ Golongan Golongan Penghamba Penghambatt VEGF VEGF Ekstrase Ekstrasel-ler l-ler
!eap"ani# na"rium (Ma>uen), se#uah ap"amer R9A, adalah salah sa"u sa"u o#a" o#a" an"i an"i8VE 8VEG G pali palin n a3al a3al 4an 4an dise" dise"uu-ui ui oleh oleh 0SD 0SDA A un"u un"uk k peno#a"an neo2as>ular AMD. Ia menika" dan mem#lok isoorm =& VEG.* Se"e Se"ela lah h 5= min minu u pen peno# o#a"a a"an, n, ma"a ma"a 4an 4an dio# dio#a" a"ii den denan an peap"ani# memiliki ke"a-aman 2isual 4an le#ih #aik, penuranan 4an siniikan siniikan "erhadap "erhadap ke"e#alan ke"e#alan re"ina sen"ral, sen"ral, dan menuran menuranii ke#u"uhan ke#u"uhan "indakan "indakan laser o"okoaulasi o"okoaulasi "erhadap "erhadap kelompok kelompok 4an sama. /aru8#aru ini, per>o#aan ase II @ III "erkon"rol se>ara a>ak melaporkan #ah3a "erapi !eap"ani# !eap"ani# dikai"kan dikai"kan denan denan hasil peninka"an peninka"an 2isual pada pasien denan denan DME sampai "ahun. )$1$1$ )$1$1$ Golongan Golongan Pengh Penghamba ambatt Ekspre Ekspresi si Resepto Reseptorr VEGF VEGF
Ali Ali#e #er>e r>ep" p" adal adalah ah usi usi "o"al "o"al pro" pro"ein ein reko rekom# m#in inan an manu manusi siaa 4an 4an menika" denan semua #en"uk VEG8A dan ak"or per"um#uhan plasen"a
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/ahkan pada dosis o#a" ini masih #ersia" hepa"o"oksik, sehina dipiloh o#a" 4an le#ih selek"i, ru#oJis"aurin. $ )$1$ )$1$:$ :$ P!6 P!6 Inhi Inhibi bito torr
!ro"ein Kinase (!K) /e"a Inhi#i"orC Ru#oJis"aurin adalah !K #e"a isoorm8selek"i inhi#i"or oral. Ini adalah se#uah o#a" un"uk peno#a"an non8prolierasi DR sedan sampai parah. !K8Dia#e"i> Re"inopa"h4 S"ud4 (!K8DRS) 4an disusun un"uk mene2aluasi eek dari ru#oJis"aurin pada hilann4a hilann4a penliha"an pasien non8prolier non8prolierasi asi DR dera-a" medera" hina hina sana" parah. Ini menun-ukkan penurunan ke-adian ke#u"aan modera" (dua kali lipa" dari sudu" 2isual) dan kehilanan penliha"an modera" lanu"an (sela (sela
#ula #ulan) n)
udi udi (!
S) -u
n-uk n-ukka ka
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%A% III !E"IMPLAN
Re"inopa"i dia#e"ik adalah salah sa"u komplikasi mikroaniopa"i kronik dari dia#e"es, dia#e"es, di"andai di"andai denan denan adan4a adan4a kerusakan kerusakan dan sum#a"an pada pem#uluh pem#uluh darah
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olo olon nan an an"i an"i#o #odi di an"i an"i VEG VEG meru merupak pakan an o#a" o#a" 4an 4an serin serin dipa dipaka kaii dalam dalam menanani re"inopa"i dia#e"ik.
DAFTAR P"TA!A
. Gus"a2 Gus"a2ian ianii R. Dianos Dianosis is dan klasiikas klasiikasii dia#e" dia#e"es es meli"u meli"us. s. DalamC /uku /uku A-ar A-ar Ilmu Ilmu !en4ak !en4aki" i" Dalam. Dalam. Edisi Edisi IV. IV. Edi"or Edi"orCC Sudo4 Sudo4o o dkk. dkk. !usa" !usa" !ener# !ener#i"an i"an
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'. h""pC@@333. h""pC@@333.ron"iersin.or@neuroenere"i>s@$.55'+@nen ron"iersin.or@neuroenere"i>s@$.55'+@nene.$$.$$$$&@ull e.$$.$$$$&@ull Hdiakses Desem#er $. $. +. i"me i"merr A9, A9, Vrensen rensen G, Va Van 9oorde 9oorden n 6, S>hlinem S>hlinemann ann R<. Vas>ular s>ular endo"helial ro3"h a>"ors and anioenesis in e4e $. disease. disease. !ro Re"in E4e Res $$5 ()C 8+.ro>k 8+.ro>ker er D6, Murad TM, Geer 6. Role o "he peri>4"e in 3ound healinC an ul"ras"ru>"ural s"ud4. EJp Mol !a"hol +*$ 5()C &8=&. . Ma2rikakis
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9opem#er $. $. Gadd S ha" is VEG h""pC@@333.3iseeek.>om@3ha"8is8an"i82e.h"m
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+. Do DV, DV, S>hmid"8Erur"h 0, Gonzalez V1, e" al. The da VI9I s"ud4C s"ud4C phase primar4 resul"s o VEG "rap8e4e in pa"ien"s 3i"h dia#e"i> ma>ular edema.
Donald A, A, Man !, e" al. !hase I and pharma>okine"i> s"ud4 o !K%, an inhi#i"or o pro"ein kinase . 6 lin ol $$ +C %'&8+. . The !K8DRS !K8DRS S"ud4 S"ud4 Group. Group. The The ee>" ee>" o ru#oJi ru#oJis"au s"aurin rin on 2isual 2isual loss in pa"ien"s 3i"h modera"el4 se2ere "o 2er4 se2ere nonproliera"i2e dia#e"i> re"in re"inop opa" a"h4 h4CC ini" ini"ial ial resu resul" l"ss o "he "he pro" pro"ei ein n kina kinase se Oinh Oinhi# i#i" i"or or dia# dia#e" e"i> i> re"inopa"h4 s"ud4 (!K8DRS) mul"i>en"er randomized >lini>al "rial. Dia#e"es $$& &%(*)C ''8+*.