Inqaku
Imethylene blue nokubona: oko kuboniswa luphando lweretina nalapho luphela khona
Umfundi ufumana isifundo apho imethylene blue yakhusela iretina, aze abuze umbuzo ozivelelayo: ngaba ifanele ifakwe esweni? Uphando lwemethylene blue nokubona aluwuphenduli loo mbuzo, kuba akukho nasinye kwizifundo eziphambili esavavanya olo setyenziso. Esinye satofa le dayi kumzimba oyijeli ongaphakathi esweni leempuku kunye netyhefu. Esinye sayongeza kulwelo lokukhulisa iiseli ezahluliweyo kwisitya selabhoratri. Esinye sayifaka kumanzi okusela eempuku ezinotshintsho lwemfuza. Isiphumo ngasinye sixhomekeke kwindlela eyasetyenziswa ngayo nakwimodeli yaso.
Eli nqaku liphonononga izifundo ezintathu zangaphambi kovavanyo lwezonyango, iintlobo ezimbini zeeseli zeretina, nomda phakathi kokhuselo kwilabhoratri nonyango lwamehlo kwizigulana. Umkhwa uyafana: imethylene blue inokuguqula uxinzelelo lweemitochondria kwiiseli zeretina phantsi kweemeko ezilawulwayo, kwaye eso siphumo asithetheleli ukufakwa emehlweni kwezisombululo ezithengiswa ezivenkileni.
Iintlobo ezimbini zeeseli, izifo ezimbini ezahlukileyo
Iretina inomaleko abaliqela, kwaye kubalulekile ukuba nguwuphi umaleko ekuthethwa ngawo. Ukukhanya kuqala kubethe iiseli ezamkela ukukhanya kwinxalenye engaphandle yeretina. Imiqondiso yazo idlula kwiiseli zemithambo-luvo eziphakathi iye kwiiseli zeganglion kwinxalenye engaphakathi yeretina, ezinemisonto ephuma ngomthambo-luvo wokubona. Umzobo ongezantsi ubiza amaleko ngokulandelelana kwawo.
Iiseli zeganglion zeretina zezona zisengozini kwiglaucoma nakumonakalo womthambo-luvo wokubona. Xa uphando kwi-intanethi lukhankanya imethylene blue neglaucoma, ludla ngokubhekisela kulo maleko wangaphakathi nakwimisonto yawo. Iiseli ezamkela ukukhanya zezona zisengozini ekuwohlokeni kwenxalenye engaphandle yeretina. Zidinga amandla amaninzi kunezinye iiseli zeretina kwaye zisebenza kufutshane nomda wazo wokuphefumla kweeseli, nto leyo ezishiya zinovimba omncinci xa isakhiwo I seemitochondria sisilela. Isiphumo kuhlobo olunye lweeseli asidluliseli kolunye, kwaye izifundo ezintathu ezingezantsi zigcina lo mahluko. Isakhono esiqhelekileyo sokwahlula iimodeli kwizigqibo sichazwa kwinqaku elithi indlela yokufunda uphando lwemethylene blue.
Iiseli zeganglion kwiliso lempuku ephilayo
Kwisifundo sokuqala kwezi zintathu, abaphandi benza imodeli yomonakalo womthambo-luvo wokubona ngokutofa isixa esincinci serotenone kumzimba oyijeli ongaphakathi kwelinye iliso lempuku, besebenzisa elinye iliso njengolawulo olufumene ulwelo oluthwala ichiza kuphela. Irotenone ithintela isakhiwo I seemitochondria, indawo yokuqala egqithisa iielektroni ezivela kwiNADH. Ukungasebenzi kakuhle kwesakhiwo I kukwayinto edibanisa le modeli nesifo somthambo-luvo wokubona esizuzwa ngemfuza sikaLeber, esichaphazela iiseli zeganglion nomthambo-luvo wokubona.
Emva kweeyure ezingamashumi amabini anesine, umaleko weeseli zeganglion kumahlo afumene irotenone wawubhityile kwaye uneeseli ezimbalwa kunamahlo olawulo. Xa imethylene blue yatofwa kunye nerotenone, loo monakalo wathintelwa ngokuxhomekeke kwisixa esinikiweyo, isixa esiphezulu esavavanywayo (0.07 mg/kg, esingaphantsi kakhulu kweLD50 yeempuku) sigcina kokubini ubukhulu bomaleko nenani leeseli. Uvavanyo oluhambelanayo kwizicubu zobuchopho ezixutywe zaba lulwelo lwabonisa iziphumo ezimbini: imethylene blue yajika uxinzelelo lokuxutywa yioksijini olubangelwe yirotenone yaza yajika nokwehla kokusetyenziswa kweoksijini. Ababhali bacebisa indlela yomonakalo obangelwa luvuselelo olugqithisileyo, apho irotenone yonakalisa iiseli zeamacrine ezilawula imiqondiso, iiseli zeganglion zikhuphe imiqondiso ngokugqithisileyo, kuze ukusebenza okuthintela ukuxutywa yioksijini kuphazamise umonakalo olandelayo. Imichiza ecetywayo njengesiseko solo khuselo ichazwe ngokweenkcukacha kwinqaku elithi iindlela esebenza ngazo imethylene blue kwiimitochondria.
Esi siphumo sinemida emithathu. Idayi yatofwa kunye netyhefu ngqo esweni, nto leyo eyindlela yokuyinika, hayi ishedyuli yonyango. Ixesha lokujonga laliyii-24 iiyure. Kwaye imilinganiselo yecytochrome oxidase yenyuka kuwo omabini amaqela onzakeleyo, nto leyo ababhali abayitolika njengokusebenza ngokugqithisileyo kunokuba ibe bubungqina bokubuyiselwa kokuphefumla kweeseli kwiretina ephilayo.
Iiseli zeganglion ezahluliweyo kwisitya selabhoratri
Isifundo sesibini salikhupha ngokupheleleyo iliso kwimodeli. Abaphandi bahlula iiseli zeganglion zeretina ezithathwe ngqo kwiimpuku eziselula baza bazichanaba kwirotenone, kwistaurosporine ebangela ukufa okucwangcisiweyo kweeseli, okanye kwiiyure ezingama-72 zeoksijini ephantsi, baza balinganisa ukuphila kwazo ngedayi eyahlula iiseli eziphilayo kwezifileyo. Imethylene blue kwi-1 ne-10 micromolar kulwelo lokukhulisa iiseli yaphucula ukuphila kwazo phantsi kwesizathu ngasinye somonakalo, malunga ne-1.5 ukuya kwi-1.9 ngokuphindaphindiweyo, ngokuxhomekeke kwimeko. Uvavanyo oluhambelanayo lwabonisa ukuba imethylene blue yagcina ukusebenza kwecytochrome c oxidase xa iiseli zazichanabeke kwihydrogen peroxide.
Olu luphando lokusebenza kwamachiza kwiiseli ezahluliweyo. Le khompawundi yafikelela kwiiseli ngokusasazeka kulwelo lokuzikhulisa kumlinganiselo ochaziweyo woxinaniso, kungekho cornea, maleko weenyembezi, lensi, mzimba oyijeli weliso, gazi linikezelwayo, okanye nkqubo yomzimba yokuzikhusela endleleni. Obo bulula yinjongo yale modeli: ibonisa ukuba iiseli zeganglion ngokwazo zinokukhuselwa xa ikhompawundi ifikelela kuzo. Ayitsho nto malunga nokuba ithontsi kumphezulu wecornea lingahambisa na naluphi na uxinaniso oluchaziweyo kwinxalenye engaphakathi yeretina. Uxinaniso olungaphezu kwe-10 micromolar lwaphetshwa ngenxa yetyhefu kwezo seli zifanayo, nto leyo ekhumbuza ukuba impendulo kwisixa esinikiweyo kwisitya selabhoratri inokuhamba kumacala omabini.
Iiseli ezamkela ukukhanya kwiimpuku ezinotshintsho lwemfuza nakumgca weeseli
Isifundo sesithathu sichaphazela inxalenye engaphandle yeretina. Abaphandi basebenzisa iimpuku zeHarlequin, ezinokusilela kwiproteni ebangela ukufa okucwangcisiweyo kweeseli, nto leyo eshiya isakhiwo I singadityaniswanga ngokupheleleyo, baza bahlola ukwakheka kweeseli ezamkela ukukhanya, iziphawuli zamacandelo angaphandle, nokugqibelela kweemitochondria xa zineenyanga ezili-11 ubudala. Imethylene blue yanikwa ukuze ifikelele kuwo wonke umzimba ngamanzi okusela emva kokulunyulwa, malunga ne-10 mg/kg ngosuku. Iimpuku ezinotshintsho lwemfuza ezaziyifumene zagcina ubukhulu obungakumbi beretina, iziphawuli ezininzi zerhodopsin neopsin, nokwakheka kweemitochondria okusempilweni ngakumbi kunezo zingayifumananga.
Umsebenzi ohambelanayo kwiiseli wasebenzisa iiseli ze-661W, umgca weeseli zempuku ofana neeseli ezamkela ukukhanya nowenziwe ukuba ukwazi ukuqhubeka usahlula, wachanabeka kwirotenone, kunye okanye ngaphandle kwemethylene blue, kangangeeyure ezingama-24. Ukuphila kweeseli kwaphucuka kwi-30 micromolar, kwaye uxinaniso olusezantsi lwabuyisela umlinganiselo weNADH kwiNAD+ kwimeko eqhelekileyo lwaza lwanciphisa uxinzelelo lokuxutywa yioksijini. Into ephawulekayo yinto engazange yenziwe yimethylene blue: ayizange ibuyisele iATP. Ukhuselo lwahambelana nokuncipha koxinzelelo lwe-redox nokuthomalala kweendlela zokuphendula kuxinzelelo, kuquka impendulo yeemitochondria kwiiproteni ezingasongwanga kunye neziphawuli zokususwa kweemitochondria, kunokubuyiselwa konikezelo lwamandla.
Lo mahluko ubalulekile kumabango emethylene blue neretina. Ikhompawundi inokugcina iseli eyamkela ukukhanya ephantsi koxinzelelo iphila ngaphandle kokulungisa ukunqongophala kwamandla ayo, nto leyo enciphisa nayiphi na inkcazelo yonyango ibe yeyoxinzelelo lwe-redox kunokuhlaziyeka ngokubanzi.
Izifundo ezintathu zithelekiswa
Uthelekiso olungezantsi luchonga isifundo ngasinye ngemodeli nangendlela yokunika imethylene blue, kuba ezo kholam zimbini zimisela oko isiphumo sinokukuxhasa.
| Isifundo | Imodeli | Indlela yokunika imethylene blue | Oko kwagcinwayo |
|---|---|---|---|
| UZhang noogxa bakhe, umonakalo womthambo-luvo wokubona kwimpuku | Iretina yempuku ephilayo eyonakaliswe yirotenone | Yatofwa kunye netyhefu kumzimba oyijeli ongaphakathi esweni | Ubukhulu bomaleko weeseli zeganglion nenani leeseli kwiiyure ezingama-24 |
| UDaudt noogxa bakhe, iiseli zeganglion ezithathwe ngqo kwiimpuku | Iiseli zeganglion ezahluliweyo zaza zakhuliswa | Yanyibilikiswa kulwelo lokukhulisa iiseli kwi-1 ukuya kwi-10 micromolar | Ukuphila kweeseli xa zichanabeke kwirotenone, kwistaurosporine, nakwioksijini ephantsi |
| UMekala noogxa bakhe, iimpuku zeHarlequin neeseli ze-661W | Ingxaki yemfuza yesakhiwo I kunye neeseli ezifana nezo zamkela ukukhanya | Amanzi okusela ane-10 mg/kg ngosuku; i-30 micromolar kulwelo lweeseli | Ukwakheka kweeseli ezamkela ukukhanya nokugqibelela kweemitochondria, ngaphandle kokubuyiselwa kweATP |
Umqolo ngamnye ungowophando lwangaphambi kovavanyo lwezonyango. Akukho mqolo waquka izigulana, walinganisa ukubona, okanye wavavanya isilungiselelo esenzelwe amehlo.
Kutheni olu ingelulo unyango lweglaucoma
Ukhathalelo lweglaucoma lwehlisa uxinzelelo olungaphakathi esweni. Ukhuselo lweeseli zemithambo-luvo luzama into eyahlukileyo: ukugcina iiseli zeganglion nemisonto yazo ziphila phantsi koxinzelelo. Izifundo ezingentla zezale njongo yesibini, hayi eyokuqala. Akukho nasinye esathoba uxinzelelo, kwaye akukho nasinye esathelekisa imethylene blue nonyango lokwehlisa uxinzelelo. Yiyo loo nto iindlela ezimiselweyo zokujongana neglaucoma nokulawula uxinzelelo zihlala zingumbuzo owahlukileyo kukhuselo lweeseli zemithambo-luvo nge-redox, kwaye yiyo loo nto isiphumo sokuphila kweeseli singenakutolikwa njengokulondolozwa kokubona.
Umahluko kwiindlela zokuyinika uqinisa le ngongoma. Ukutofa kunye enye into kumzimba oyijeli weliso kubeka isixa esaziwayo ecaleni kweretina ngexesha lomonzakalo. Ukuyinika ngamanzi okusela kuchanaba isilwanyana siphela kangangeenyanga, uxinaniso lwayo kwiretina lungaziwa. Ulwelo lokukhulisa iiseli luchanaba iiseli ezingenazithintelo ngokuthe ngqo. Akukho nanye kwezi eqikelela ukuba lingakanani icandelo lesixa esifakwe kumphezulu weliso eliya kudlula kwicornea, lingakhukuliseki ziinyembezi, lidlule kwilensi nakumzimba oyijeli, lize lifike kuwo nawuphi na umaleko weretina kuxinaniso olunokuba luncedo. Loo ngxaki yokufikisa le nto kwindawo efunekayo yinxalenye yombuzo obanzi weendlela zokunika nokusasazeka kwemethylene blue, apho indlela nganye ifuna imilinganiselo yayo yoxinaniso.
Umahluko kwizicubu wongeza umqobo wesibini. Idayi efikelela ngaphambili kwiliso ayikafikeleli ngasemva kwalo, kwaye uxinaniso olunceda omnye umaleko lunokwenzakalisa omnye. Izisombululo ezithengiswa ezivenkileni azenziwa, azibulawelwa iintsholongwane, azilungiswa ukuze kugcinwe i-pH, okanye zigcinwe njengezilungiselelo zamehlo, kwaye ukucoceka, i-pH, uxinaniso lwamasuntswana anyibilikileyo, nezithako ezincedisayo zonke zibalulekile xa zichukumisa icornea okanye zingena ngaphakathi esweni. Akukho nto kwezi ziphumo zeretina eqinisekisa ukufaneleka kokufaka ezo zisombululo ngaphakathi okanye kumphezulu weliso. Imibuzo ngemigangatho yokulungiselela inxulumene nokhuseleko nokuphathwa kwemethylene blue.
Apho ubungqina buphela khona
Xa efundwa kunye, la maphepha mathathu axhasa ibango elilinganiselweyo: phantsi kweemeko ezilawulwayo, imethylene blue inokuthomalalisa uxinzelelo lwe-redox lweemitochondria kwiiseli zemithambo-luvo zeretina ize igcine ukwakheka kwazo. Ibango liphela apho ziphela khona ezo meko. Iimodeli zesakhiwo I ezenziwe ngetyhefu okanye ngemfuza aziyoglaucoma, iidrusen, okanye isifo esinxulumene neswekile. Amaxesha amafutshane okujonga nemilinganiselo yokwakheka azithethi ukubona okuhlala kugcinwe. Kwaye uxinaniso olukhuselayo kwelinye icandelo aluthethi isixa esifanele elinye.
Ubungqina obomeleleyo ngakumbi bungafuna izinto ezahlukileyo: uxinaniso oluchaziweyo olufikelela kwiretina emva kokusebenzisa indlela enokusetyenziswa kunyango, imilinganiselo yokusebenza kokubona kwizilwanyana, inzuzo engaxhomekekanga kuxinzelelo kwimodeli efanelekileyo kwiglaucoma, kuze kulandele idatha yokhuseleko nokusebenza ebantwini. De ezo zinto zibekho, imethylene blue nokubona kuhlala kuyingqikelelo yophando enemida ecacileyo: ukusebenza kwayo kwiimitochondria zeretina kunesiseko esinokubakho, kodwa kuboniswe kuphela kwiiseli nakwizilwanyana, kungekho ndlela isuka kwezi zifundo iye kunyango lwamehlo.