! 38! 8 Vol.38NO.8 2018 08 JOURNALOFGANNANMEDICALUNIVERSITY AUG.2018 XY + I 1,D 2,! 2 ( 1.2015 ;2.+,;3.!"#$,-. 341000) :( ^ 6 \ J `",, ; Sb 6,( 6, WHI'Q >6]6% HI Y5 X( HI'Q6,D4'Q 1( * L KL+6 HX,'Q 2 \( 6 `" Q, 3 X( 'Q 6 H #$%:( ;= NF 2;'Q &' :R775 (:A )* :1001-5779(2018)08-0830-05 DOI:10.3969/j.isn.1001-5779.2018.08.027 Advancesingenetherapyofglaucoma PENGJin yan 1,ZHONGJia ning 2,WANGHui 3 (GannanMedicalUniversity1.PostgraduateStudent,Grade2015;2.ResearchCenter;3.DepartmentofOphthalmology, TheFirstAfiliatedHospitalofGannanMedicalUniversity,Ganzhou,Jiangxi341000) Abstract:Glaucomaisacommonandseriouslyharmfuldiseasethatcancauseireversibleblindnes,andsofarthereis noefectivetreatmenttopreventthedevelopmentofthedisease.inrecentyears,alargenumberofstudieshavefound thatthepathogenesisiscloselyrelatedtothestructuralandfunctionalabnormalitiesofrelatedgenes.withthefurtherre searchonthegenerelatedtothepathogenesisofglaucoma,andthegenetherapytrialswidelycariedoutinmammals suchasrats,genetherapywilbecomeoneoftheimportantdirectionsforthefuturetreatmentofglaucoma.therefore, thisarticlewilreviewthelatestresearchongenetherapyofglaucoma. Keywords:Glaucoma;Retinalganglioncels;Genetherapy ( (Glaucoma)^" 6 G3 ( -^=NF) ] Q6, ; %J=NF >= 6)?, Q( 6 "6 8 6000, 2020 8 8000 [1] D 6, J ^( 6 Q>, = NF 2 (Retinalganglion cels,rgcs)6 \ ^( 6 Q [2] Q,7 # D4/ =6]^( 6 T 'Q ^;3 'Q,< ) 6 a,ab 6U,, QMW( HI6'Q,-;3( * L KL, 'Q1( 3*+6 Q, 'Q ( ab 6 9: 1 XY 9#+ I Y5 U1( +6K,,_;6D 10 ( 6HI'Q 'Q786%,;3 > < G 4?,S ( 6 > [3] Stone* [4] 1 X J X L ( +,-: ' (\K:81760160);-. (\K:GJ170882); (\K:QD201605)./01:",,,, :%&7$ U Email:zhongning_003@163.com./01:,,, S, :S, ;, Email:gyfywanghui@163.com 830
8 =,* ( 'Q (Primaryopenangleglaucoma,POAG) 6A +,D Myocilin(MYOC)'Q^ POAG6 6 'Q`" Joe* [5],MYOCA R S ; 2 % 46], ;?BG?P, S 4( 6 2(Cyclooxygenase 2,COX 2)^ M> (Prostaglandins,PGs) 2 + 6 PGs \? ; + 26 >, ;?BG,?P 6 6 M>,7 >,]b Z[( " 6, T `, Maihofner* [6],POAG ">BH E> S6 JX L( " 1 G 2+ COX 278 6,- COX 26 J PGs1 +6 1, Masferer* [7] I BH E> ]c COX 2678 7 ;3'Q, H 2> 2 COX 2'Q,?P COX 24 PGs678,b\]8 Z 6 6 ( " # T, ;3 3Ja # ^,1 M6 W\ U+,?@ 3;, S a S, ^ > C(MitomycinC, MMC)*T?@ ] (W& 3Ja 62 6, ^ 1 O * M - [8] p21rs^ p21'q786, ;3 -c 2A RS JE 6 J 2A,c Tenon2 2?@,Q \< 3 M W6\ 3* [9], >HI Q B(myocardin relatedtranscriptionfactor B,MRTF B)1 Tenon2 2 +;I, b MRTF'Q\ > [10] Q,7] 'Q c M Tenon2 26? @, ^Q 3; 6 () ( "6 RGCsE WNF Q b I J N F Q (Brain derived neurotrophicfactor,bdnf)1c NF 2E, NF 6 I >NF M6 >W + 45 Perez,WordingerRJ* [11-12],BDNF4 Q< 1DE BQ< (TyrosinekinasereceptorsB,TrkB)1( 6 RGCs + b 678 Karim* [13],BDNF 1 POAG " Z+6 [ XY" M BDNFabc ( RGCs M6 2E [14-16] Dreyer* [17],( NF 26E W= +3 (1 D 6 J J b 6I Koe berle* [18],O 2 JNF Q (Glialcel line derivedneurotrophicfactor,gdnf)] ;3 = + MülerO 2786(1D K< GLAST / ( ^ RGCs 6E Q,;3P:NF Q 678 / RGCs 2 ( 'Q 6 `" 2 XY + 1 6'Q ab" ' 6, :(1)+ Qa ;(2) 6<, ['Q \ C ;(3) = 6 1,] <6 U, 6; >'Q ; UVUF [19],6b, [20] 4F <, ; J U 4 _ KL6 +, 'Q678 4 T`, " Z[( KL6 4/ RGCs 2.1 CD + " Shen* [21], MYOCA RS;3 RhoGTP 4 RhoE 8W 6JK; X 26 >,?P F ; ;?6BG 2; C3 (C3)^ RhoGTP 6 %Jc R S Liu* [22] M < 6 C3'Q _<;= 6 2+, C3'Q78\c RhoGTP 4 # 6JK;, 26 2 4 2` #,-] & 0= 6 ;? Tian* [23] ",; 3 RhoE c Y 27632c RhoGTP 6^ U RhoE \?P <( > 6? Q,;3c MYOCA R S6^ JK; 2, RhoGTP > RhoE,?P ; 6 Z[ 6 2 ( 'Q 6+ `" Baraza* [24] 1 KL+, < COX 2'Q 4 PGsQ<'Q1 < H 2> +!? 78 L,COX 278 M, PGs;3 PGsQ< 2^ JK;, Z F ; ;?6BG, 4? WZ[, ' Q 6 ",sirna (SmalinterferingRNA,siRNA)1( 6'Q 831
2018 + C M6U sirna^i 20~25+ D6 RNA,\;3 Z J RNAS 'Q 'Q78 [25-26] Pintor* [27] 1 + X D > M>Q<'Q6 sirna, 7 2 Q c,( Z[ b `;, 2HI6 4 ; \D 'Q b>'q 6 D 6 2,Z[ 2.2 + " Perkins* [9]. S(6 R b M, 1D ' 6 ^ p21'q6 M (rad.p21) <; 7,F rad.p21 6 Tenon2 2 DNA 2> 2 I Jc < 7,rAd.p21]c 3Ja M6 W\ >?,c W MMCH ; ` $% MMCHI6-, 6]J 3 1 " rad.p21'q 6 U,Wen* [28] X( rad.p21m,rad.p216 < 1 +6 'Q78? U,4 1F +6 >UVUF*@A 7, ^ rad.p21m, ', bf 01! 4NM P [J 1 3Ja M, rad.p21 _ ^, MO ; J? U,! 14NTW XY S $% &,rad.p21'q ]1( 3Ja M; b 6T? @ ;, X 3 M W 6T, Yu* [10], 6 TX " abq< J6 < ) sirna*`,l Tenon2 2+6 MRTF B'Q, ;3 ^ sirna, b 3 70%6 MRTF B'Q, b B 2 21 2;' +6, 8 B ( 3a M W 6 2.3 P + " Park,Igarashi* [29-30] BDNF'Q 6NF < 2,X K +%6( ( KL <X = ^X M, RGCs6 XY?P, BDNFX?K +% 6 2E abc Ko* [31] ",1 J( KL6 = +, RS6 BDNF'Q1 RGCs+63 78 & RGCs6 b6^, 832 BDNF'Q _ MülerO 2 I RGCs 6 T`, 7 O 21NF/ + ] 4,^'Q 6 V [32] b ` ;,Li* [33] MHI < TrkB'Q _<;= 6 RGCs+, RGCs+ BDNF Q< TrkB6378\_ =NF %M6 RGCs ^;3 TrkB?P! 3 E (phosphatidylinositol3 kinase,pi3k)/akt J, \ _E > 2;JK E (extracelu larsignal regulatedkinase,erk), NF 'Q678 camp U RS(cAMP responseelementbindingprotein,creb)6 D E, Z_ RGCs [34] ;,Hu* [35], TrkBE 29D71 JE TrkB,SD ( ( KL+ RGCs6 C, 7 TrkB^` ( 6 1 7 BDNF TrkBJK; ^( 6I" + V6 Checa Casalengua,SembaK* [36-37] DBA/ 2J ( KL,1 < b GDNF6B, GDNF RGC6 I T` Koeberle* [38],GDNF];3 PI3K Src4 MAPKJK;, ;(1D K <(GLAST)1 MülerO 2+6378, ; / RGCs6 1 GLAST6 sirnam,gdnf ;6 GLAST sirna T, 7 GLAST\]^( 'Q 6I"+ 2.4, + " UE 8W <M J 6 > 1, UEWS >( bi; 1 M, UE]S bk J M6 7, I 6 UE ^ ( NF 6 Q Sacca,BrennanLA* [39-40],T X J ab/ Jiang,WuJH * [41-42] " ( J KL, 5 b (Superoxidedismutase,SOD2)'Q 6MHI _( = M,\$% SOD2 'Q78?P,, T RGCs Q,T UE ^ C " 6( 'Q 3 Z ( 'Q N,1
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