Methylene blue nekuona: zvinoratidzwa netsvakurudzo yeretina uye painogumira

Muverengi anowana chidzidzo umo methylene blue yakadzivirira retina, obva abvunza mubvunzo unongouya woga: inofanira kuiswa muziso here? Tsvakurudzo yemethylene blue nekuona haipinduri mubvunzo iwoyo, nokuti hapana pazvidzidzo zvikuru chakaedza kushandiswa ikoko. Chimwe chakabaya dhayi iyi muvitreous yembeva pamwe chete nechinhu chine chepfu. Chimwe chakaiwedzera mumvura yekukurisa masero yakanga yakakomberedza masero akaparadzaniswa ari mundiro. Chimwe chakaiisa mumvura yekunwa yembeva dzine majini akachinja. Zvakawanikwa pachidzidzo chimwe nechimwe zvinofanira kunzwisiswa maererano nenzira yekuipinza nemodhi yakashandiswa.

Chinyorwa ichi chinotsanangura zvidzidzo zvitatu zvisati zvasvika pakuedzwa muvanhu, mhando mbiri dzemasero eretina, uye muganhu uripo pakati pekudzivirira masero murabhoritari nekurapa maziso muvarwere. Zvinoonekwa zvakafanana: methylene blue inogona kushandura kushushikana kwemitochondria mumasero eretina pasi pemamiriro anodzorwa, asi zvakawanikwa izvozvo hazvipi chikonzero chekuisa zvinonyungudutswa zvinotengeswa muziso.

Mhando mbiri dzemasero, zvirwere zviviri zvakasiyana

Retina ine zvikamu zvakaturikidzana, uye chikamu chiri kutaurwa chinokosha. Chiedza chinotanga kurova masero anogamuchira chiedza ari muchikamu chekunze cheretina. Zviratidzo zvawo zvinopfuura nomumasero etsinga ari pakati zvichienda kumasero eganglion eretina ari muchikamu chemukati, ane maaxon anobuda netsinga yekuona. Mufananidzo uri pazasi unopa mazita ezvikamu izvi zvichitevedzana.

Masero eganglion eretina ndiwo ari panjodzi muglaucoma uye muzvirwere zvetsinga yekuona. Kana tsvakiridzo dzepamhepo dzichitaura nezvemethylene blue neglaucoma, dzinowanzoreva chikamu ichi chemukati nemaaxon acho. Masero anogamuchira chiedza ndiwo ari panjodzi pakuora kwechikamu chekunze cheretina. Ndiwo anoda simba rakawanda kupfuura mamwe masero eretina uye anoshanda pedyo nemuganhu wekufema kwawo kwemasero, izvo zvinoasiya aine simba shoma rakachengetwa kana complex I yemitochondria ikatadza kushanda. Zvakawanikwa mumhando imwe yemasero hazvingonzi zvinoshandawo mune imwe, uye zvidzidzo zvitatu zviri pazasi zvinodzichengeta dzakaparadzana. Unyanzvi hwekusiyanisa mamodhi nezvinopedziswa kubva maari hunotsanangurwa mukuverenga tsvakurudzo yemethylene blue.

Masero eganglion muziso rembeva mhenyu

Muchidzidzo chekutanga pazvitatu izvi, vatsvakurudzi vakagadzira modhi yechirwere chetsinga yekuona nokubaya rotenone nemwero muduku muvitreous yeziso rimwe rembeva, vachishandisa rimwe ziso sekuenzanisa kwakapiwa mvura yekutakura rotenone chete. Rotenone inovhara complex I yemitochondria, nzvimbo yokutanga inopfuudza maerekitironi anobva kuNADH. Kutadza kushanda kwecomplex I ndiko zvakare kunobatanidza modhi iyi neLeber hereditary optic neuropathy, chirwere chinogarwa nhaka chinobata masero eganglion netsinga yekuona.

Mushure memaawa makumi maviri nemana, chikamu chemasero eganglion mumaziso akapiwa rotenone chakanga chatetepa uye chine masero mashoma kupfuura maziso ekuenzanisa. Apo methylene blue yakabayiwa pamwe chete nerotenone, kukuvara ikoko kwakadzivirirwa zvichienderana nemwero wakapiwa, uye mwero mukuru wakaedzwa (0.07 mg/kg, uri pasi zvikuru peLD50 yembeva) wakachengetedza ukobvu nehuwandu hwemasero. Miedzo yakaitwa panguva imwe chete pamatishu europi akapwanyiwa kuti asanganiswe yakaratidza zvinhu zviviri: methylene blue yakadzorera kumashure kushushikana kunokonzerwa neoxidation kwakakonzerwa nerotenone uye kuderera kwekushandiswa kweokisijeni. Vanyori vakafungidzira nzira yekukuvadzwa nekukurudzirwa kwakawandisa, umo rotenone inokuvadza masero eamacrine anodzora zviratidzo, masero eganglion achitumira zviratidzo zvakawandisa, uye kushanda kweantioxidant kuchimisa kukuvara kunozotevera. Maitiro emakemikari anofungidzirwa kuti ndiwo anoita kudzivirira uku anotsanangurwa zvakadzama mumaitiro emethylene blue mumitochondria.

Zvakawanikwa izvi zvine miganhu mitatu. Dhayi yakabayiwa pamwe chete nechinhu chine chepfu zvakananga muziso, inova nzira yekuipinza, kwete chirongwa chekurapa. Nguva yekucherechedza yaiva maawa 24. Uye zviyero zvecytochrome oxidase zvakakwira mumapoka ose maviri akanga akuvadzwa, izvo zvakadudzirwa nevanyori sekushanda kwakawandisa pane kuva humbowo hwekuti kufema kwemasero kwakanga kwadzorerwa muretina mhenyu.

Masero eganglion akaparadzaniswa ari mundiro

Chidzidzo chechipiri chakasiya ziso rose kunze kwemuedzo. Vatsvakurudzi vakaparadzanisa masero eganglion eretina akatorwa zvakananga kumakonzo maduku ndokuaisa parotenone, staurosporine inokonzera kufa kwemasero kwakarongwa, kana maawa 72 eokisijeni yakaderera, ndokuyera kupona vachishandisa dhayi inosiyanisa masero mapenyu neakafa. Methylene blue iri pamwero we1 ne10 micromolar mumvura yekukurisa masero yakavandudza kupona pakukuvadza kwechinhu chimwe nechimwe, kusvika pakapetwa kanenge 1.5 kusvika 1.9 zvichienderana nemamiriro acho. Mumwe muedzo wakabatana nawo wakaratidza kuti methylene blue yakachengetedza kushanda kwecytochrome c oxidase masero paakaiswa pahydrogen peroxide.

Uku kuongorora kushanda kwechinhu pamasero akaparadzaniswa. Chinhu ichi chakasvika pamasero nokupararira nomumvura yekukurisa masero pamwero wakatarwa, pasina cornea, rukoko rwemisodzi, lens, vitreous, kuyerera kweropa, kana hurongwa hwekudzivirira muviri munzira. Kureruka ikoko ndicho chinangwa chemodhi iyi: inoratidza kuti masero eganglion pachawo anogona kudzivirirwa kana chinhu ichi chasvika paari. Haitauri chinhu pamusoro pekuti donhwe riri pamusoro pecornea ringasvitsa mwero wakatarwa muchikamu chemukati cheretina here. Mimwe mwero iri pamusoro pe10 micromolar yakadziviswa nokuda kwechepfu yayo kumasero mamwe chete iwayo, chiyeuchidzo chokuti zvinoitika nokuchinja mwero mundiro zvinogona kuva zvakanaka kana zvakaipa.

Masero anogamuchira chiedza mumbeva dzine majini akachinja uye mumutsara wemasero

Chidzidzo chechitatu chine chokuita nechikamu chekunze cheretina. Vatsvakurudzi vakashandisa mbeva dzeHarlequin, dzine kushomeka kweapoptosis inducing factor kunosiya complex I isina kuunganidzwa zvakakwana, ndokuongorora chimiro chemasero anogamuchira chiedza, zviratidzo zvezvikamu zvawo zvekunze, uye kugara kwemitochondria yakakwana mbeva padzakanga dzine mwedzi 11. Methylene blue yakapiwa kuti isvike mumuviri wose nomumvura yekunwa mushure mokurumurwa, pamwero waiva ungangoita 10 mg/kg pazuva. Mbeva dzine majini akachinja dzakapiwa methylene blue dzakachengetedza retina yakakora zvikuru, zviratidzo zverhodopsin neopsin zvakawanda, uye chimiro chemitochondria chaiva nani kupfuura dzisina kuipiwa.

Basa remasero rakabatana nechidzidzo ichi rakashandisa masero e661W, mutsara wemasero embeva akafanana neanogamuchira chiedza uye anokwanisa kuramba achiwanda murabhoritari, akaiswa parotenone aine kana asina methylene blue kwemaawa 24. Kupona kwakavandudzwa pa30 micromolar, uye mimwe mwero yakaderera yakadzorera reshiyo yeNADH kuNAD+ payakajairika uye yakaderedza kushushikana kunokonzerwa neoxidation. Chinhu chinonyanya kucherechedzwa ndechezvisina kuitwa nemethylene blue: haina kudzoreredza ATP. Kudzivirirwa kwakafambirana nokuderedzwa kwekushushikana kweredox uye kudzikama kwenzira dzinopindura kushushikana, kusanganisira mhinduro yemitochondria kumapuroteni asina kupetwa nemazvo uye zviratidzo zvemitophagy, pane kudzoreredzwa kwekuwanikwa kwesimba.

Musiyano iwoyo unokosha pazvinotaurwa nezvemethylene blue neretina. Chinhu chinogona kuchengeta sero rinogamuchira chiedza rakashushikana riri benyu chisina kugadzirisa kushomeka kwaro kwesimba, izvo zvinoganhurira chero dudziro ine chokuita nekurapa pakushushikana kweredox pane kuvandudzwa kwakazara.

Kuenzanisa zvidzidzo zvitatu

Kuenzanisa kuri pazasi kunoratidza chidzidzo chimwe nechimwe nemodhi uye nzira yekuipinza, nokuti makoramu maviri iwayo ndiwo anotaridza zvinogona kutsigirwa nezvakawanikwa.

Mutsara wose ndewechidzidzo chisati chasvika pakuedzwa muvanhu. Hapana mutsara wakabatanidza varwere, wakayera kuona, kana wakaedza mushonga wakagadzirirwa kushandiswa muziso.

Nei uku kusiri kurapa glaucoma

Kutarisira glaucoma kunoderedza kumanikidzwa kwemvura iri mukati meziso. Kudzivirira masero etsinga kunoedza chimwe chinhu chakasiyana: kuchengeta masero eganglion nemaaxon awo ari mapenyu paanenge achishushikana. Zvidzidzo zviri pamusoro ndezvechinangwa chechipiri, kwete chekutanga. Hapana chazvo chakaderedza kumanikidzwa ikoko, uye hapana chakaenzanisa methylene blue nekurapa kunoderedza kumanikidzwa. Ndicho chikonzero nzira dzagara dzichishandiswa pakutarisira glaucoma nokudzora kumanikidzwa dzichiramba dziri nyaya yakasiyana nekudzivirira masero etsinga kuburikidza neredox, uye nei kupona kwemasero kusingagoni kududzirwa sokuchengetedzwa kwekuona.

Kusiyana kwenzira dzekuipinza kunosimbisa pfungwa iyi. Kubaya pamwe chete muvitreous kunoisa huwandu hunozivikanwa pedyo neretina panguva yekukuvara. Kupa mwero mumvura yekunwa kunosvitsa chinhu ichi kumhuka yose kwemwedzi yakawanda, mwero unosvika muretina usingazivikanwi. Mvura yekukurisa masero inosvitsa chinhu ichi zvakananga kumasero asina matishu akaapoteredza. Hapana pane izvi chinofanotaura kuti chikamu chipi chemwero unoiswa pamusoro peziso chingayambuka cornea, chosara pashure pokubviswa nemisodzi, chopfuura nelens nevitreous, chosvika mune chimwe chezvikamu zveretina pamwero unobatsira. Dambudziko iri rekusvitsa chinhu kunzvimbo yacho chikamu chemubvunzo wakafara wenzira dzekupinza methylene blue nekupararira kwayo mumuviri, umo nzira imwe neimwe inoda zviyero zvayo zvemwero unosvika kumatishu.

Kusiyana kwematishu kunowedzera chimhingamupinyi chechipiri. Dhayi inosvika kumberi kweziso haisati yasvika kumashure kwaro, uye mwero unobatsira chimwe chikamu ungakuvadza chimwe. Zvinonyungudutswa zvinotengeswa hazvigadzirwi, hazvibviswi utachiona, hazvigadziriswi kuti pH igare yakadzikama, uye hazviisirwi zvinozvichengetedza semishonga yakagadzirirwa maziso; kuchena, pH, osmolality, nezvimwe zvinosanganiswa zvose zvinokosha pakusangana necornea uye mukati meziso. Hapana mune zvakawanikwa izvi pamusoro peretina chinotsigira kuisa zvinonyungudutswa zvakadaro mukati meziso kana pamusoro paro. Mibvunzo pamusoro pemitemo yekugadzirira inofanira kutariswa pamwe chete nekuchengeteka uye mabatirwo emethylene blue.

Panogumira humbowo

Kana zvaverengwa pamwe chete, zvinyorwa zvitatu izvi zvinotsigira pfungwa yakaganhurirwa: pasi pemamiriro anodzorwa, methylene blue inogona kuderedza kushushikana kweredox mumitochondria yemasero etsinga eretina uye kuchengetedza chimiro chawo. Pfungwa iyi inogumira panogumira mamiriro iwayo. Mamodhi ekukanganisika kwecomplex I kunokonzerwa nechepfu kana nemajini haasi glaucoma, drusen, kana chirwere chine chokuita nechirwere cheshuga. Nguva pfupi dzekucherechedza nezviyero zvechimiro hazvirevi kuona kunoramba kuripo. Uye mwero unodzivirira mune imwe nzvimbo hausi mwero wekupa mune imwe.

Humbowo hwakasimba zvikuru hungada zvikamu zvakasiyana: mwero unozivikanwa unosvika muretina mushure mokushandisa nzira inogoneka pakurapa varwere, zviyero zvekushanda kwekuona mumhuka, kubatsira kusingabvi pakuderedza kumanikidzwa mumodhi inoenderana neglaucoma, uyezve ruzivo rwekuchengeteka nekushanda muvanhu. Kusvikira izvi zvavapo, methylene blue nekuona zvinoramba zviri pfungwa inoda kuedzwa netsvakurudzo ine miganhu yakajeka: kushanda kunogoneka pamitochondria muretina, kwakaratidzwa mumasero nemhuka chete, pasina nzira inobva muzvidzidzo izvi ichienda kukurapa maziso.