Iimveliso

I-Sigma receptor 1 (σR1) yi-non-opioid transmembrane protein enokuthi isebenze njenge-molecular chaperone kwi-endoplasmic reticulum-mitochondrial membrane.Ii-Ligands ze-σR1, ezifana (+)-pentazocine [(+)-PTZ], zinika i-retinal neuroprotection ephawulweyo kwi-vivo kunye ne-vitro.Kutshanje siye sahlalutya i-retinal phenotype yeempuku eziswele i-σR1 (σR1 KO) kwaye sajonga i-retinal morphology eqhelekileyo kunye nokusebenza kwiimpuku ezincinci (iiveki ezi-5-30) kodwa zinciphile iimpendulo ezingezizo (nSTRs), ilahleko ye-retinal ganglion cell (RGC), kunye nokuphazamiseka. ye-optic nerve axons ehambelana nokungasebenzi kakuhle kwe-retinal yangaphakathi ngu-1 unyaka.Ezi datha zisikhokelele ukuba sivavanye i-hypothesis yokuba i-σR1 inokuba yinto ebalulekileyo ekukhuseleni uxinzelelo olungapheliyo lwe-retinal;Isifo seswekile sisetyenziswe njengemodeli yoxinzelelo olungapheliyo.Ukuqinisekisa ukuba i-σR1 iyadingeka kwi-(+)-PTZ imiphumo ye-neuroprotective, ii-RGC eziphambili ezihlukanisiweyo kuhlobo lwasendle (WT) kunye ne-σR1 KO iimpuku ziye zavezwa kwi-xanthine-xanthine oxidase (10 µM: 2 mU / ml) ukubangela uxinzelelo lwe-oxidative phambi okanye ukungabikho kwe (+) -PTZ.Ukufa kweseli kwavavanywa ngohlalutyo lwe-terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).Ukuvavanya imiphumo yoxinzelelo olungapheliyo kumsebenzi we-RGC, isifo sikashukela senziwe kwi-3-iveki ye-C57BL / 6 (WT) kunye ne-σR1 KO iigundane, usebenzisa i-streptozotocin ukuvelisa amaqela amane: i-WT nondiabetic (WT non-DB), i-WT diabetic (WT-DB) ), σR1 KO non-DB, kunye σR1 KO-DB.Emva kweeveki ze-12 zesifo sikashukela, xa iigundane zineeveki ze-15 ubudala, uxinzelelo lwe-intraocular (IOP) lwabhalwa, uvavanyo lwe-electrophysiologic lwenziwa (kubandakanywa nokufunyanwa kwe-nSTRs), kwaye inani le-RGCs libalwe kumacandelo e-retinal histological.Izifundo ze-in vitro zibonise ukuba +Kwizifundo zoxinzelelo olungapheliyo olubangelwa sisifo sikashukela, i-IOP ilinganiswe kumaqela amane egundane yayingaphakathi kwinqanaba eliqhelekileyo;nangona kunjalo, kukho ukwanda okubalulekileyo kwi-IOP ye-σR1 KO-DB iimpuku (16 ± 0.5 mmH g) xa kuthelekiswa namanye amaqela avavanyiweyo (σR1 KO non-DB, WT non-DB, WT-DB: ~12 ± 0.6 mmHg ).Ngokumalunga nokuvavanywa kwe-electrophysiologic, i-nSTRs ye-σR1 KO iigundane ezingekho ze-DB zazifana neegundane ze-WT ezingekho ze-DB kwiiveki ze-15;nangona kunjalo, bezisezantsi kakhulu kwi-σR1 KO-DB iimpuku (5 ± 1 µV) xa kuthelekiswa namanye amaqela, kubandakanywa, ngokukodwa, σR1 KO-nonDB (12±2 µV).Njengoko kulindelekile, inani le-RGCs kwi-σR1 KO non-DB iigundane zifana neegundane ze-WT ezingekho ze-DB kwiiveki ze-15, kodwa phantsi koxinzelelo olungapheliyo lwesifo sikashukela kwakukho ii-RGC ezimbalwa kwii-retina ze-σR1 KO-DB iigundane.Le yingxelo yokuqala ebonisa ngokungathandabuzekiyo ukuba iziphumo ze-neuroprotective ze (+)-PTZ zifuna σR1.σR1 KO iimpuku zibonisa ubume beretina eqhelekileyo kunye nomsebenzi kwiminyaka emincinci;nangona kunjalo, xa uphantsi koxinzelelo olungapheliyo lwesifo seswekile, kukho ukukhawuleza kokushoda kokusebenza kwe-retinal kwi-σR1 KO iimpuku kangangokuba ukungasebenzi kweseli ye-ganglion kubonwa kwiminyaka engaphambili kakhulu kune-nondiabetic σR1 KO iimpuku.Idatha ixhasa i-hypothesis yokuba i-σR1 idlala indima ephambili kuxinzelelo lwe-retinal ye-modu kwaye inokuba yinto ekujoliswe kuyo ebalulekileyo kwisifo se-retinal.