Isihloko
I-methylene blue nokubona: lokho okuvezwa ucwaningo lwe-retina nokuthi luphelela kuphi
Umfundi uthola ucwaningo lapho i-methylene blue yavikela khona i-retina, bese ebuza umbuzo olindelekile: ingabe kufanele ifakwe esweni? Ucwaningo nge-methylene blue nokubona aluwuphenduli lowo mbuzo, ngoba asikho ezifundweni ezibalulekile esahlola lokho kusetshenziswa. Esinye sajova udayi ku-vitreous yamagundane kanye nobuthi. Esinye sayifaka oketshezini olwaluzungeze amangqamuzana ahlukanisiwe esitsheni sokuhlola. Esinye sayifaka emanzini aphuzwa amagundane anoguquko lwezakhi zofuzo. Umphumela ngamunye uqondene nendlela yokuyifaka nemodeli esetshenzisiwe.
Lesi sihloko sihlola izifundo ezintathu zangaphambi kokuhlolwa kubantu, izinhlobo ezimbili zamangqamuzana e-retina, nomngcele phakathi kokuvikelwa elabhorethri nokwelashwa kwamehlo kubantu. Okubonakalayo kuyafana: i-methylene blue ingaguqula ingcindezi ye-mitochondria emangqamuzaneni e-retina ngaphansi kwezimo ezilawulwayo, kodwa lowo mphumela awukuthetheleli ukufaka izixazululo ezithengiswayo esweni.
Izinhlobo ezimbili zamangqamuzana, izifo ezimbili ezihlukene
I-retina inezingqimba, futhi kubalulekile ukuthi iyiphi ingqimba okukhulunywa ngayo. Ukukhanya kuqala kufinyelele emangqamuzaneni amukela ukukhanya engxenyeni engaphandle ye-retina. Izimpawu zawo zidlula emangqamuzaneni ezinzwa aphakathi ziye emangqamuzaneni e-ganglion engxenyeni engaphakathi ye-retina, ama-axon awo aphuma ngenzwa yokubona. Umdwebo ongezansi uveza amagama ezingqimba ngokulandelana kwazo.
Amangqamuzana e-ganglion e-retina yiwo asengozini ku-glaucoma nasezifweni zenzwa yokubona. Lapho ukusesha kukhuluma nge-methylene blue ne-glaucoma, ngokuvamile kusuke kukhulunywa ngale ngqimba yangaphakathi nama-axon ayo. Amangqamuzana amukela ukukhanya yiwo asengozini ekuwohlokeni kwengxenye engaphandle ye-retina. Yiwo adinga amandla amaningi kunawo wonke ku-retina futhi asebenza eduze komkhawulo wawo wokuphefumula kwamangqamuzana, okuwashiye enomthamo omncane osalayo lapho i-complex I ye-mitochondria ihluleka. Umphumela otholwe ohlotsheni olulodwa lwamangqamuzana awudluleli kolunye, futhi izifundo ezintathu ezingezansi ziyazihlukanisa lezi zinhlobo. Ikhono elijwayelekile lokuhlukanisa amamodeli neziphetho lichazwa esihlokweni esithi indlela yokufunda ucwaningo lwe-methylene blue.
Amangqamuzana e-ganglion esweni legundane eliphilayo
Esifundweni sokuqala kulezi ezintathu, abacwaningi bakha imodeli yesifo senzwa yokubona ngokujova inani elincane le-rotenone ku-vitreous yeso elilodwa legundane, besebenzisa elinye iso njengesilinganiso sokuqhathanisa esithola kuphela uketshezi oluthwala into ejovwayo. I-rotenone ivimba i-complex I ye-mitochondria, okuyindawo yokuqala edlulisela ama-electron asuka ku-NADH aya phambili. Ukungasebenzi kahle kwe-complex I kuyisici futhi esixhumanisa le modeli nesifo sofuzo sika-Leber senzwa yokubona, okuyisifo samangqamuzana e-ganglion nenzwa yokubona.
Ngemva kwamahora angu-24, ungqimba lwamangqamuzana e-ganglion emehlweni afakwe i-rotenone lwaluzacile futhi lunamangqamuzana ambalwa kunamehlo okuqhathanisa. Lapho i-methylene blue ijovwa kanye ne-rotenone, lowo monakalo wavinjwa ngendlela eyayincike esilinganisweni esisetshenzisiwe, isilinganiso esiphakeme kunazo zonke esahlolwa (0.07 mg/kg, esingaphansi kakhulu kwe-LD50 yegundane) salondoloza kokubili ukujiya kwengqimba nenani lamangqamuzana. Ukuhlola okuhambisanayo kumasampula obuchopho agaywe axutshwa kwabonisa imiphumela emibili: i-methylene blue yaguqula ingcindezi ye-oxidative eyayibangelwe yi-rotenone futhi yaguqula ukwehla kokusetshenziswa komoya-mpilo. Ababhali baphakamisa indlela yokulimala ngenxa yokushukunyiswa ngokweqile, lapho i-rotenone ilimaza khona amangqamuzana e-amacrine alawula izimpawu, amangqamuzana e-ganglion athumele izimpawu ngokweqile, bese isenzo sokulwa ne-oxidation siphazamisa umonakalo obangelwa yilokho. Ikhemistri ephakanyisiwe yalokho kuvikelwa ichazwe kabanzi esihlokweni esithi izindlela i-methylene blue esebenza ngazo ku-mitochondria.
Kunemingcele emithathu ehambisana nalo mphumela. Udayi wajovwa kanye nobuthi ngqo esweni, okuyindlela yokufaka into, hhayi uhlelo lokwelapha. Isikhathi sokubheka sasiy amahora angu-24. Futhi izilinganiso ze-cytochrome oxidase zakhuphuka kuwo womabili amaqembu alimazekile, okuyinto ababhali abayihumusha njengokusebenza ngokweqile kunokuba kube ubufakazi bokubuyiselwa kokuphefumula kwamangqamuzana ku-retina ephilayo.
Amangqamuzana e-ganglion ahlukanisiwe esitsheni sokuhlola
Isifundo sesibili sasingasebenzisi iso nhlobo. Abaphenyi bahlukanisa amangqamuzana okuqala e-ganglion e-retina kumagundane amancane, base bewachaya ku-rotenone, ku-staurosporine ebangela ukufa kwamangqamuzana okuhleliwe, noma esimweni somoya-mpilo ophansi amahora angu-72, base belinganisa ukusinda ngodayi ohlukanisa amangqamuzana aphilayo nafile. I-methylene blue engu-1 no-10 micromolar oketshezini lokukhulisa amangqamuzana yathuthukisa ukusinda lapho ebhekene nento ngayinye elimazayo, cishe izikhathi ezingu-1.5 kuya ku-1.9 kuye ngesimo. Ukuhlola okuhambisana nalokhu kwabonisa ukuthi i-methylene blue yalondoloza ukusebenza kwe-cytochrome c oxidase ngesikhathi amangqamuzana echaywa ku-hydrogen peroxide.
Lokhu kuyisayensi yokusebenza kwezinto emangqamuzaneni ahlukanisiwe. Le nhlanganisela yafinyelela emangqamuzaneni ngokusabalala oketshezini lokuwakhulisa ezingeni lokugxila elichaziwe, kungekho i-cornea, ungqimba lwezinyembezi, ilensi, i-vitreous, ukugeleza kwegazi, noma amasosha omzimba endleleni. Lokho kulula kuyinhloso yale modeli: ibonisa ukuthi amangqamuzana e-ganglion ngokwawo angavikelwa lapho le nhlanganisela ifinyelela kuwo. Ayisho lutho ngokuthi iconsi elibekwe ebusweni be-cornea lingaletha yini izinga lokugxila elichaziwe engxenyeni engaphakathi ye-retina. Amazinga angaphezu kuka-10 micromolar agwenywa ngenxa yobuthi kulawo mangqamuzana afanayo, okuyisikhumbuzo sokuthi indlela amangqamuzana asabela ngayo esilinganisweni esitsheni sokuhlola ingaba yinzuzo noma ibe yingozi.
Amangqamuzana amukela ukukhanya kumagundane anoguquko lwezakhi zofuzo nasohlwini lwamangqamuzana
Isifundo sesithathu siphathelene nengxenye engaphandle ye-retina. Abacwaningi basebenzisa amagundane e-Harlequin, antula isici esibangela ukufa kwamangqamuzana okuhleliwe, okushiya i-complex I ingahlanganisiwe ngokuphelele, futhi bahlola ukwakheka kwamangqamuzana amukela ukukhanya, izimpawu zezingxenye zangaphandle, nokuphelela kwesakhiwo se-mitochondria eneminyaka eyizinyanga ezingu-11. I-methylene blue yanikezwa ukuze isabalale emzimbeni wonke ngamanzi okuphuza ngemva kokulunyulwa, cishe ngo-10 mg/kg ngosuku. Amagundane anoguquko lwezakhi zofuzo ayitholile alondoloza ukujiya okwengeziwe kwe-retina, izimpawu eziningi ze-rhodopsin ne-opsin, nesakhiwo se-mitochondria esinempilo engcono kunalawo angayitholanga.
Umsebenzi ohambisanayo emangqamuzaneni wasebenzisa amangqamuzana e-661W, okuwuhlu lwamangqamuzana egundane afana namangqamuzana amukela ukukhanya futhi aguqulwe ukuze aqhubeke nokuhlukana, achaywa ku-rotenone ene-methylene blue noma engenayo amahora angu-24. Ukusinda kwathuthuka ku-30 micromolar, futhi amazinga okugxila aphansi abuyisela isilinganiso se-NADH ne-NAD+ esimweni esijwayelekile anciphisa nengcindezi ye-oxidative. Imininingwane egqamayo yilokho i-methylene blue engakwenzanga: ayizange ibuyisele i-ATP. Ukuvikelwa kwakuhambisana nokuncipha kwengcindezi ye-redox nokuthuliswa kwezindlela zokuphendula ingcindezi, okuhlanganisa impendulo ye-mitochondria kumaprotheni angasongekile nezimpawu ze-mitophagy, hhayi ukubuyiselwa kokuhlinzekwa kwamandla.
Lowo mehluko ubalulekile ezimangalweni nge-methylene blue ne-retina. Inhlanganisela ingagcina ingqamuzana elamukela ukukhanya elicindezelekile liphila ngaphandle kokulungisa ukushoda kwalo kwamandla, okwenza noma iyiphi incazelo yokwelapha igxile engcindezini ye-redox kunasekubuyiseleni ubusha ngokubanzi.
Izifundo ezintathu ziqhathaniswa
Ukuqhathanisa okungezansi kuhlonza isifundo ngasinye ngemodeli nangendlela yokufaka i-methylene blue, njengoba lezo zinhlu ezimbili zinquma ukuthi umphumela ungasekela ini.
| Isifundo | Imodeli | Indlela yokufaka i-methylene blue | Okwalondolozwa |
|---|---|---|---|
| U-Zhang nozakwabo, isifo senzwa yokubona egundaneni | I-retina yegundane eliphilayo elinyazwe yi-rotenone | Yajovwa ku-vitreous kanye nobuthi | Ukujiya kongqimba lwamangqamuzana e-ganglion nenani lamangqamuzana ngemva kwamahora angu-24 |
| U-Daudt nozakwabo, amangqamuzana okuqala e-ganglion egundane | Amangqamuzana e-ganglion ahlukanisiwe akhuliswa elabhorethri | Yancibilikiswa oketshezini lokukhulisa amangqamuzana ku-1 kuya ku-10 micromolar | Ukusinda kwamangqamuzana lapho echaywa ku-rotenone, ku-staurosporine nasekuntulekeni komoya-mpilo |
| U-Mekala nozakwabo, amagundane e-Harlequin namangqamuzana e-661W | Isici sofuzo ku-complex I kanye namangqamuzana afana nalawo amukela ukukhanya | Amanzi okuphuza ngo-10 mg/kg ngosuku; 30 micromolar oketshezini lwamangqamuzana | Ukwakheka kwamangqamuzana amukela ukukhanya nokuphelela kwesakhiwo se-mitochondria, ngaphandle kokubuyiselwa kwe-ATP |
Umugqa ngamunye ungowocwaningo lwangaphambi kokuhlolwa kubantu. Awukho umugqa owafaka iziguli, walinganisa ukubona, noma wahlola umkhiqizo owakhelwe ukusetshenziswa emehlweni.
Kungani lokhu kungekona ukwelashwa kwe-glaucoma
Ukunakekelwa kwe-glaucoma kwehlisa umfutho ongaphakathi esweni. Ukuvikelwa kwamangqamuzana ezinzwa kuzama okunye: ukugcina amangqamuzana e-ganglion nama-axon awo ephila ngaphansi kwengcindezi. Izifundo ezingenhla ziphathelene nomzamo wesibili, hhayi owokuqala. Asikho kuzo esehlisa umfutho, futhi asikho esaqhathanisa i-methylene blue nokwelashwa okwehlisa umfutho. Yingakho izindlela ezisunguliwe zokubhekana ne-glaucoma nokulawula umfutho zihlala zingumbuzo ohlukile ekuvikelweni kwamangqamuzana ezinzwa nge-redox, nokuthi kungani umphumela wokusinda kwamangqamuzana ungeke uhunyushwe njengokulondolozwa kokubona.
Umehluko ezindleleni zokufaka ugcizelela leli phuzu. Ukujova kanye ku-vitreous kubeka inani elaziwayo eduze kwe-retina ngesikhathi sokulimala. Ukunikeza ngamanzi okuphuza kuchaya isilwane sonke izinyanga eziningi, izinga lokugxila ku-retina lingaziwa. Uketshezi lokukhulisa amangqamuzana luchaya amangqamuzana angavikelwe ngokuqondile. Akukho kulokhu okubikezela ukuthi iyiphi ingxenye yesilinganiso esifakwe ebusweni beso engadlula ku-cornea, isale ngemva kokukhukhulwa yizinyembezi, idlule kwilensi naku-vitreous, bese ifinyelela kunoma iyiphi ingqimba ye-retina ezingeni lokugxila eliwusizo. Leyo nkinga yokufinyelela iyingxenye yombuzo obanzi wezindlela zokufaka nokusabalala kwe-methylene blue, lapho indlela ngayinye idinga izilinganiso zayo zamazinga okugxila.
Umehluko ezicutshini wengeza isithiyo sesibili. Udayi ofinyelela engxenyeni engaphambili yeso awukafinyeleli engxenyeni engemuva, futhi izinga lokugxila elisiza ingqimba eyodwa lingalimaza enye. Izixazululo ezithengiswayo azenziwa, azibulawelwa amagciwane, azilungiselelwa ukugcina i-pH izinzile, futhi azifakelwa izilondolozi njengamalungiselelo okusetshenziswa emehlweni; ubumsulwa, i-pH, i-osmolality nezithasiselo konke kubalulekile lapho i-cornea nengaphakathi leso kuchaywa kukho. Akukho kule miphumela ye-retina okuqinisekisa ukufaka izixazululo ezinjalo ngaphakathi noma ebusweni beso. Imibuzo ngezindinganiso zokulungiselela ihambisana nokuphepha nokuphathwa kwe-methylene blue.
Lapho ubufakazi buphelela khona
Uma efundwa ndawonye, amaphepha amathathu asekela isimangalo esinomkhawulo: ngaphansi kwezimo ezilawulwayo, i-methylene blue inganciphisa ingcindezi ye-redox ye-mitochondria emangqamuzaneni ezinzwa e-retina futhi ilondoloze ukwakheka kwawo. Leso simangalo siphela lapho lezo zimo ziphelela khona. Amamodeli obuthi nawokukhubazeka kwe-complex I okubangelwa yizakhi zofuzo awafani ne-glaucoma, i-drusen, noma isifo esihlobene nesifo sikashukela. Izikhathi ezimfushane nezilinganiso zokwakheka azisho ukubona okuqhubeka isikhathi eside. Futhi izinga lokugxila elivikelayo engxenyeni eyodwa alisona isilinganiso sokusebenzisa kwenye.
Ubufakazi obunamandla kakhulu bungadinga izingxenye ezihlukene: izinga elichaziwe lokuchayeka kwe-retina ngemva kokufaka ngendlela esebenzisekayo ekwelapheni, izilinganiso zokusebenza kokubona ezilwaneni, inzuzo engancikile emfundweni esweni kumodeli ehambisana ne-glaucoma, bese kuba idatha yokuphepha nokusebenza kubantu. Kuze kube yilapho lokho kutholakala, i-methylene blue nokubona kusalokhu kungumbono osazohlolwa ocwaningweni onemingcele ecacile: ukusebenza kwayo ku-mitochondria ye-retina kunesisekelo esizwakalayo, kodwa kuboniswe emangqamuzaneni nasezilwaneni kuphela, kungekho ndlela esuka kulezi zifundo iye ekwelapheni amehlo.