Imikhiqizo

I-Sigma receptor 1 (σR1) iyiphrotheni ye-transmembrane engeyona i-opioid engase isebenze njenge-molecular chaperone kulwelwesi lwe-endoplasmic reticulum-mitochondrial.Ama-Ligands we-σR1, afana no-(+)-pentazocine [(+)-PTZ], anikeza i-retina neuroprotection ephawulwe ku-vivo kanye ne-in vitro.Muva nje sihlaziye i-retinal phenotype yamagundane antula i-σR1 (σR1 KO) futhi sabona i-retinal morphology evamile kanye nokusebenza kumagundane amancane (amaviki angama-5-30) kodwa sanciphisa izimpendulo ezingezinhle ze-scotopic threshold (nSTRs), ukulahleka kwe-retinal ganglion cell (RGC), kanye nokuphazamiseka. ye-optic nerve axon ehambisana nokungasebenzi kahle kwe-retinal ngonyaka ongu-1.Le datha isiholele ekuhloleni i-hypothesis yokuthi i-σR1 ingase ibaluleke kakhulu ekugwemeni ukucindezeleka okungapheli kwe-retina;Isifo sikashukela sisetshenziswe njengemodeli yokucindezeleka okungapheli. Ukuze kunqunywe ukuthi i-σR1 iyadingeka yini (+) -PTZ imiphumela ye-neuroprotective, ama-RGC ayinhloko ahlukanisiwe ohlotsheni lwasendle (WT) kanye namagundane angu-σR1 KO achayeke ku-xanthine-xanthine oxidase (10 µM: 2 mU/ml) ukuze udale ingcindezi ye-oxidative uma kukhona noma ungekho (+)-PTZ.Ukufa kweseli kwahlaziywa ngokuhlaziywa kwe-terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL).Ukuhlola imiphumela yengcindezi engapheli emsebenzini we-RGC, isifo sikashukela senziwe evikini le-3 C57BL/6 (WT) kanye namagundane e-σR1 KO, kusetshenziswa i-streptozotocin ukukhiqiza amaqembu amane: i-WT nondiabetic (WT non-DB), i-WT yesifo sikashukela (WT-DB ), σR1 KO non-DB, kanye no-σR1 KO-DB.Ngemuva kwamaviki angu-12 esifo sikashukela, lapho amagundane esenamaviki angu-15 ubudala, ukucindezela kwe-intraocular (IOP) kwabhalwa, ukuhlolwa kwe-electrophysiologic kwenziwa (kuhlanganise nokutholwa kwe-nSTRs), futhi inani lama-RGCs labalwa ezigabeni ze-retinal histological. Ucwaningo lwe-In vitro lubonise ukuthi (+)-PTZ ayikwazanga ukuvimbela ukufa okubangelwa ingcindezi ye-oxidative kwama-RGC avunwe kumagundane angu-σR1 KO kodwa anikeze isivikelo esiqinile ngokumelene nokufa kwama-RGC avunwe kumagundane e-WT.Ezifundweni zokucindezeleka okungapheli okubangelwa isifo sikashukela, i-IOP elinganiswa emaqenjini amane amagundane yayingaphakathi kwebanga elijwayelekile;kodwa-ke, kube nokukhuphuka okukhulu kwe-IOP yamagundane e-σR1 KO-DB (16 ± 0.5 mmH g) uma kuqhathaniswa namanye amaqembu ahloliwe (σR1 KO non-DB, WT non-DB, WT-DB: ~12 ± 0.6 mmHg ).Ngokuphathelene nokuhlolwa kwe-electrophysiologic, ama-nSTRs we-σR1 KO non-DB amagundane ayefana namagundane e-WT angewona ama-DB kumaviki e-15;kodwa-ke, abephansi kakhulu kumagundane angu-σR1 KO-DB (5 ± 1 µV) uma kuqhathaniswa namanye amaqembu, okuhlanganisa, ikakhulukazi, i-σR1 KO-nonDB (12±2 µV).Njengoba bekulindelekile, inani lama-RGC ku-σR1 KO amagundane angewona ama-DB lalifana namagundane e-WT angewona ama-DB emavikini angu-15, kodwa ngaphansi kwengcindezi engapheli yesifo sikashukela kwakukhona ama-RGC ambalwa kuma-retina amagundane angu-σR1 KO-DB. Lona umbiko wokuqala okubonisa ngokungananazi ukuthi imiphumela ye-neuroprotective ye-(+)-PTZ idinga u-σR1.I-σR1 KO amagundane abonisa ukwakheka okujwayelekile kwe-retina kanye nokusebenza ebudaleni;kodwa-ke, uma ungaphansi kwengcindezi engapheli yesifo sikashukela, kukhona ukusheshisa kokushoda kokusebenza kwe-retina kumagundane angu-σR1 KO kangangokuthi ukungasebenzi kahle kwe-ganglion cell kubonwa eminyakeni engaphambi kwalokho kakhulu kunamagundane angenayo isifo sikashukela σR1 KO.Idatha isekela i-hypothesis yokuthi i-σR1 idlala indima ebalulekile ekucindezelekeni kwe-retinal ye-modu futhi ingase ibe into ebalulekile ekuhlosweni kwesifo se-retina.